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Sample records for cancer squamous intraepithelial

  1. Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.

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    Morrison, C; Catania, F; Wakely, P; Nuovo, G J

    2001-10-01

    The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.

  2. Anal squamous intraepithelial lesions in HIV+ MSM

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, M.L.

    2018-01-01

    In this thesis we report on several aspects of high-grade anal squamous intraepithelial lesions (HSIL) in HIV+ men who have sex with men (MSM). It is estimated that 10% of HIV+ MSM with anal HSIL will develop anal squamous cell carcinoma (ASCC) over 30 years time. Screening programs similar to

  3. Prevalence of high-grade squamous intraepithelial lesions and cervical cancer among patients with unsatisfactory colposcopic examination, without visible lesion

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    Fernanda Rangel da Veiga

    Full Text Available CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL, the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%, glandular dysplasia (1.5% and absence of disease (33.8%. CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.

  4. Prevalence and severity of cervical squamous intraepithelial lesion ...

    African Journals Online (AJOL)

    Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross-sectional hospital-based descriptive study was ...

  5. PREVALENCE OF HUMAN PAPILLOMAVIRUS GENOTYPES IN LOW AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AT CERVICAL TISSUE

    OpenAIRE

    Prasetyo, Rizki Eko; Mastutik, Gondo; Mustokoweni, Sjahjenny

    2017-01-01

    HPV infection is known to cause cervical cancer. This study aimed to identify the variant of HPV genotypes of cervical precancerous lesions from low grade squamous intraepithelial lesion  (LSIL) and high grade squamous intraepithelial lesion (HSIL). This was an explorative study using formalin fix paraffin embedded (FFPE) from cervical precancerous lesions at Dr. Soetomo Hospital, Surabaya. DNA was extracted from FFPE and hybridized for HPV genotyping using Ampliquality HPV Type Express kit (...

  6. Abnormal anal cytology risk in women with known genital squamous intraepithelial lesion

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    Maria do Socorro Nobre

    2016-05-01

    Full Text Available The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64. Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5% had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR = 2.46; p = 0.03. In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR = 2.81; p = 0.02. This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer.

  7. Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H cannot be ruled out

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    Andréa Cytryn

    Full Text Available CONTEXT AND OBJECTIVE: The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS into ASC-US (undetermined significance and ASC-H (high-grade intraepithelial lesion cannot be ruled out. The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF with ASC-H cytology, and compare them with ASC-US cases. DESIGN AND SETTING: Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. METHODS: ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis was taken as the gold standard. RESULTS: The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55% and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764. Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83; P = 0.2786998. There were no uterine cervical cancer cases. CONCLUSION: The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

  8. Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out.

    Science.gov (United States)

    Cytryn, Andréa; Russomano, Fábio Bastos; Camargo, Maria José de; Zardo, Lucília Maria Gama; Horta, Nilza Maria Sobral Rebelo; Fonseca, Rachel de Carvalho Silveira de Paula; Tristão, Maria Aparecida; Monteiro, Aparecida Cristina Sampaio

    2009-09-01

    The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

  9. Cervical squamous and glandular intraepithelial neoplasia: identification and current management approaches Neoplasia intraepitelial cervical escamosa y glandular: identificación y estrategias de manejo

    OpenAIRE

    V Cecil Wright

    2003-01-01

    Certain types of human papillomaviruses (HPV) are associated with squamous intraepithelial lesions and cancer and these are termed high-risk. HPV type 16 is detected in approximately half of the high-grade squamous intraepithelial lesions and cancer. Because of the high rate of spontaneous regression of low-grade squamous lesions, follow-up by cytology, colposcopy and possible biopsy appears preferable. Due to the higher rate of progression to malignancy of the high-grade lesions conservative...

  10. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  11. Correlation between cervical cancer and squamous intraepithelial lesion with the vaginal microenvironment changes%阴道微环境改变与宫颈病变的相关性分析

    Institute of Scientific and Technical Information of China (English)

    杨少岩; 吴潇; 李杰; 赵卫东

    2017-01-01

    Objective To research the correlation between cervical cancer and squamous intraepithelial lesion with the imbalance of vaginal microenvironment.Methods A total of 318 outpatients were assigned into two groups,of which 159 women diagnosed with cervical cancer or squamous intraepithelial lesion by pathology were selected as experimental group,and the other 159 women without cervical lesions were selected as control group.Results The detection rates of HPV,BV,AV,trichomonas of experiment group were 88.05%,39.62%,33.33% and 13.21% respectively,which significantly higher than those in control group (P4.5、菌群多样性异常(I、IV级)和过氧化氢阳性的比例分别为50.31%、55.35%、59.75%和72.33%,显著高于对照组(P<0.05).结论 阴道内病原体感染可能增加宫颈病变发生,阴道微环境改变是参与宫颈病变发生发展的重要因素之一.

  12. Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping

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    Omar Clavero

    2017-06-01

    Full Text Available Background: Human papillomavirus (HPV-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ. We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and –positive patients. Methods: Histopathology identified 47 squamous intraepithelial lesions (SILs adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Results: Sixteen (16/47 of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47 were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM; Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Conclusions: Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative. Keywords: Anal squamocolumnar junction, Low-grade squamous intraepithelial lesion (LSIL, High-grade squamous intraepithelial lesion (HSIL, Papillary immature metaplasia (PIM, HPV, HIV

  13. Morphological features of basal membrane of stratified squamous epithelium and underlying stroma in cervical intraepithelial neoplasias and cancer of the uterine cervix

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    Oksana M. Pliten

    2015-06-01

    Kharkiv National Medical University   Abstract. The article presents the morphological features of the basal membrane of stratified squamous epithelium and underlying stroma in cervical intraepithelial neoplasias and cancer of the uterine cervix which were investigated by routine histological, histochemical and immunohistochemical methods. The present study indicated that as stages of carcinogenesis progress changes in the stromal-vascular component and in the basal membrane of the epithelium occur that has an important role in the differential diagnosis of the stages of carcinogenesis of the uterine cervix. Key words: uterine cervix, cervical intraepithelial neoplasias, cancer, stratified squamous epithelium, basal membrane, stroma, morphology.   Резюме. У роботі розглянуті морфологічні особливості базальної мембрани багатошарового плоского епітелію і підлягаючої строми при цервікальних інтраепітеліальних неоплазіях та раку шийки матки, які були досліджені за допомогою рутинних гістологічних, гістохімічних і імуногістохімічних методів. Дослідження показало, що у міру поважчання стадії канцерогенезу відбуваються зміни стромально-судинного компоненту і базальної мембрани епітелію. Виявлені зміни мають важливу роль у диференціальній діагностиці стадій канцерогенезу у шийці матки. Ключові слова: шийка матки, цервікальні інтраепітеліальні неоплазії, рак, багатошаровий плоский епітелії, базальна

  14. World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

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    Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

    2012-01-01

    It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

  15. Squamous cell cancer (image)

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    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  16. Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva

    DEFF Research Database (Denmark)

    Faber, Mette T; Sand, Freja Lærke; Albieri, Vanna

    2017-01-01

    In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were...... used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model...... samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions....

  17. High grade squamous intraepithelial lesion in inmates from Ohio: cervical screening and biopsy follow-up

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    Rofagha Soraya

    2006-01-01

    Full Text Available Abstract Background Cervical carcinoma remains the second leading cause of cancer death in women worldwide and sexual behavior is regarded as the main contributing factor. We studied cervical cytology screening with surgical biopsy follow-up in women prisoners and compared the findings to those in the general population. Methods We reviewed 1024 conventional cervical smears, 73 cervical biopsies and 2 loop electrosurgical excision procedure (LEEP specimens referred to us from the Correctional Center in Columbus, Ohio during a 12-month period. The results were compared to 40,993 Pap smears from the general population for the same 12-month period. Results High grade squamous intraepithelial lesion (HGSIL was diagnosed in 1.3% of the cervical smears from the inmate population versus 0.6% in the general population (p < 0.01. The unsatisfactory rate was 1.6% compared to 0.3% in the general population (p < 0.01. Among the study population, follow-up tissue diagnosis was obtained in 24.3% of the abnormal cytology results (ASCUS, LGSIL, and HGSIL. Of the HGSIL Pap smears, 61.5% had a subsequent tissue diagnosis. Thirty-nine biopsies (52% of the all inmate biopsies and LEEP showed CIN II/III (cervical intraepithelial neoplasia II/III. Eight of these thirty-nine follow-up biopsies diagnosed as CIN II/III had a previous cervical cytology diagnosis of ASCUS. The average age for HGSIL was 30.5 years (S.D. = 5.7 and for low grade squamous intraepithelial lesion (LGSIL was 27.2 years (S.D. = 6.1. Conclusion A significantly higher prevalence of HGSIL cervical cytology and unsatisfactory smears was encountered in female inmates, with tissue follow-up performed in less than two thirds of the patients with HGSIL. These results are in keeping with data available in the literature suggesting that the inmate population is high-risk and may be subject to less screening and tissue follow-up than the general population. Clinicians should proceed with urgency to improve

  18. Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis

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    Caroline Alves de Oliveira

    Full Text Available CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001 in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164, although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients.

  19. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

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    Darin Ruanpeng

    Full Text Available Anal cancer, one of human papillomavirus (HPV related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM and HIV-infected (HIV+ persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL using Papanicolau (Pap screening among MSM in northern Thailand and its associated factors.Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification.Mean age was 27.2 years (range 18-54. Overall, 86 (43.0% had ASIL: 28 (14.2% with atypical cells of undetermined significance (ASCUS, 1 (0.5% with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H, 56 (28.4% with low-grade squamous intraepithelial lesion (LSIL, and 1 (0.5% with high-grade squamous intraepithelial lesion (HSIL. ASIL was associated by univariate analysis (p ≤0.05 with older age, gender identity other than bisexual (i.e., gay men and transgender women, rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002 and HIV infection (p = 0.01.ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA, not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

  20. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

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    Ruanpeng, Darin; Chariyalertsak, Suwat; Kaewpoowat, Quanhathai; Supindham, Taweewat; Settakorn, Jongkolnee; Sukpan, Kornkanok; Utaipat, Utaiwan; Miura, Toshiyuki; Kosashunhanan, Natthapol; Saokhieo, Pongpun; Songsupa, Radchanok; Wongthanee, Antika

    2016-01-01

    Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. Mean age was 27.2 years (range 18-54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

  1. Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group.

    Science.gov (United States)

    2000-03-01

    Human papillomavirus (HPV) infections appear to be central to the development of cervical cancer. This study addresses the question of whether testing women who have low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix for HPV DNA is useful as a triage strategy. Four clinical centers in different areas of the United States participated in a randomized clinical trial of the use of HPV DNA testing in women with cytologic evidence of atypical squamous cells of undetermined significance (ASCUS) or LSIL. The study sample in this article consists only of women who had LSIL at enrollment. Within 6 months of an LSIL diagnosis (based on a Pap smear read by a community-based cytopathologist), women who were 18 years of age or older completed a standardized questionnaire and underwent a pelvic examination that included collection of cervical specimens for HPV DNA testing by Hybrid Capture II (HCII)(R) assay. Among the 642 women referred with LSIL who had analyzable test results, the mean chronologic age and age at first coitus were similar among the four clinical centers, despite the centers' ethnic and geographic diversity. Overall, HPV DNA was detected in cervical samples from 532 (82.9%) of the 642 women (95% confidence interval = 79.7%-85.7%). This high frequency of HPV positivity was confirmed by polymerase chain reaction (PCR) assays in a subset of 210 paired specimens tested by HCII and PCR (81.4% were positive by both methods). Because a very high percentage of women with an LSIL diagnosis from Pap smears are positive for HPV DNA by HCII testing, there is limited potential for this assay to direct decisions about the clinical management of women with LSIL. The role of HPV testing in the management of women with ASCUS is still under study.

  2. Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study

    NARCIS (Netherlands)

    Wensveen, Celesta; Kagie, Marjolein; Veldhuizen, Roel; de Groot, Christianne; Denny, Lynette; Zwinderman, Koos; Trimbos, Baptist

    2003-01-01

    (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting

  3. Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion: a category with an increased outcome of high-grade lesions: use as a quality assurance measure.

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    Nishino, Ha T; Wilbur, David C; Tambouret, Rosemary H

    2012-08-01

    "Low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) is an increasingly used, equivocal interpretive category in gynecologic cytology. In an effort to evaluate its potential usefulness as a measure of quality assurance, we studied patterns of use of the LSIL-H diagnosis compared with "LSIL" and "high-grade squamous intraepithelial lesion" (HSIL) with corresponding histologic outcomes for 10 cytopathologists in our practice. In our laboratory, while the overall rate of associated cervical intraepithelial neoplasia 2 or greater on histologic follow-up for LSIL-H was intermediate between that of LSIL and HSIL, the outcomes for individual cytopathologists varied widely. Monitoring this particular utilization-outcome data with periodic confidential feedback to individual cytopathologists offers an opportunity for practice improvement within a laboratory and serves as an additional measure of quality assurance. These data may be useful for establishing and/or realigning the diagnostic criteria for this equivocal cytologic interpretation endorsed by a pathology practice.

  4. Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

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    Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

    2016-01-01

    To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

  5. The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Munk, Christian; Thomsen, Birthe Lykke

    2006-01-01

    BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important...... for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high......-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high...

  6. EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR AND HUMAN PAPILLOMAVIRUS (HPV L1 CAPSID PROTEIN IN CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS

    Directory of Open Access Journals (Sweden)

    Balan Raluca

    2010-09-01

    Full Text Available We analyzed the immunohistochemical pattern of epidermal growth factor receptor (EGFR in cervical squamous intraepithelial lesions (SILs in correlation with L1 HPV capsid protein, in order to determine the relationship between EGFR expression and the infection status of human papillomavirus (HPV. The study included 40 cases, 24 LSIL (low grade SIL (CIN1, cervical intraepithelial neoplasia and 16 HSIL (high grade SIL (6 cases of CIN2 and 10 cases of CIN3. The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR was immunohistochemically evaluated on the corresponding cervical biopsies. The HPV L1 capsid protein was expressed in 45.83% of LSIL and 25% of HSIL. EGFR was overexpressed in 62,4% of HSIL (58,4% CIN2 and 41,6% CIN3 and 37,6% LSIL. The immunoexpression of L1 HPV has clinical application in the progression assessment of the cervical precancerous lesions without a correlation to the grade of the cervical SIL. EGFR is expressed by all proliferating squamous epithelial cells, thus corresponding with the grade of SIL. The evaluation of EGFR status, correlated with L1 HPV protein expression, can provide useful data of progression risk of cervical squamous intraepithelial lesions

  7. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  8. Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions.

    Science.gov (United States)

    Chumworathayi, Bandit; Thinkhamrop, Jadsada; Blumenthal, Paul D; Thinkhamrop, Bandit; Pientong, Chamsai; Ekalaksananan, Tipaya

    2010-02-01

    To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation). HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types. Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P=0.94). Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  9. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

    NARCIS (Netherlands)

    van de Nieuwenhof, Hedwig P.; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G.; Massuger, Leon F. A. G.; van der Zee, Ate G. J.; de Hullu, Joanne A.; van Kempen, Leon C. L. T.

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a

  10. Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

    Science.gov (United States)

    Jahic, Mahira; Mulavdic, Mirsada; Hadzimehmedovic, Azra; Jahic, Elmir

    2013-01-01

    To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

  11. Prevalence of Primary HPV in Djibouti: Feasibility of Screening for Early Diagnosis of Squamous Intraepithelial Lesions.

    Science.gov (United States)

    Petrelli, Alessio; Di Napoli, Anteo; Giorgi Rossi, Paolo; Rossi, Alessandra; Luccini, Daniele; Di Marco, Ilaria; Traoré, Amadou Laico; Gillio Tos, Anna; Trevisan, Morena; Mirisola, Concetta; Costanzo, Gianfranco

    2016-10-01

    In many African Sub-Saharan countries, human papilloma virus (HPV) prevalence data are not available. The current study estimated the prevalence of HPV virus in the female population of Djibouti. Approximately 1000 asymptomatic women 16 to 64 years old were enrolled from 3 of the main health structures of Djibouti in 2014 and 2015; 998 cervical samples were tested for HPV-DNA of high risk types, 499 during the first year, and 499 during the second. Positive samples were typed with an HPV genotyping kit. The women were an average age of 38.8 years (SD, 10.2); 54 women tested positive for HPV (prevalence rate, 5.4% [95% confidence interval, 4.0-6.8]). The highest prevalence was observed among the women younger than 35 years. HPV66 was the most prevalent (15.4% of the infections), followed by HPV31 and HPV52 (10.8% both) and HPV16 (9.2%). All 54 women who tested HPV-positive underwent a Pap test, which was positive in 8 cases (14.8%): 2 high-grade squamous intraepithelial lesion (HSIL) and 6 low-grade (LSIL). The HPV prevalence shows a curve by age similar to that of other African countries. The proportion of HPV16 is among the lowest ever seen in similar studies. The findings suggest to Djibouti the choice of a strategy of screening that includes forms of cytological triage, thus limiting recourse to colposcopy.

  12. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    Science.gov (United States)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  13. Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests

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    Flávia de Miranda Corrêa

    Full Text Available CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid test for triage of low-grade squamous intraepithelial lesions (LSIL requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3, in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%. The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS, was available in two studies (33% and 90.8%; and specificity was available in one study (53%. CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

  14. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

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    Brooke R Koltz

    2013-01-01

    Full Text Available Introduction: Automated screening of Thin Prep ® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep ® Imaging System (TIS. Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H and high-grade squamous intraepithelial lesion (HGSIL results on Thin Prep ® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07. The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study′s initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33% of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32% were interpreted as ASC-H and 164 (0.35% were interpreted as HGSIL. During the same time period automated screening (TIS was performed on 23,111 Pap tests. Interpretation of 62 (0.27% cases provided an ASC-H result, while 71 (0.31% were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71

  15. Comparison of the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low-grade and high-grade squamous intraepithelial lesions across different age groups.

    Science.gov (United States)

    Paluszkiewicz, Aleksandra; Pruski, Dominik; Iwaniec, Kinga; Kędzia, Witold

    2017-01-01

    To assess the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low grade and high-grade squamous intraepithelial lesions across different age groups. The study included 1103 patients, age 25-70 years. All patients underwent in-depth diagnostic tests following either an abnormal Pap test result or a clinically suspicious cervical lesion. In all women the following examinations were performed: a molecular test detecting 14 high-risk types of HPV, a colposcopy examination, as well as directed-biopsy of the cervix. The studied population was subdivided into four age groups. It was observed that the percentage of high grade squamous intraepithelial lesions (HSIL) and cancers increased with women's age. Sensitivity of both methods for detecting high-grade squamous intraepithelial lesions was highest for women aged 40-49 years. Sensitivity values of HPV testing was higher than that of cervical cytology among women under age 50. Specificity of HPV testing increased significantly with age of women and was several fold higher across all age groups than the specificity of cervical cytology.

  16. Cervical squamous and glandular intraepithelial neoplasia: identification and current management approaches Neoplasia intraepitelial cervical escamosa y glandular: identificación y estrategias de manejo

    Directory of Open Access Journals (Sweden)

    V Cecil Wright

    2003-01-01

    Full Text Available Certain types of human papillomaviruses (HPV are associated with squamous intraepithelial lesions and cancer and these are termed high-risk. HPV type 16 is detected in approximately half of the high-grade squamous intraepithelial lesions and cancer. Because of the high rate of spontaneous regression of low-grade squamous lesions, follow-up by cytology, colposcopy and possible biopsy appears preferable. Due to the higher rate of progression to malignancy of the high-grade lesions conservative treatment is recommended. One of the most common reasons for persistence relates to the human immunodeficiency virus. Adenocarcinoma in situ is an uncommon disorder and not well identified by cytologic sampling or colposcopic inspection. The diagnosis is made by cone biopsy, the specimen having negative margins for disease. Hysterectomy is the treatment procedure of choice unless fertility is an issue. Excisional methods (particularly electrosurgical loop can interfere with accurate histological interpretation in some cases of both squamous disease and adenocarcinoma in situ.Ciertos tipos de virus del papiloma humano (VPH, denominados de alto riesgo, están asociados con lesiones escamosas intraepiteliales y cáncer invasor. El VPH tipo 16 es detectado en aproximadamente la mitad de las lesiones escamosas intraepiteliales de alto grado y cáncer. Sin embargo, existe una elevada proporción de regresión espontánea en lesiones escamosas de bajo grado, por lo que para su monitoreo es preferible la utilización de citología, colposcopía y biopsia. Asimismo, debido a la elevada tasa de progresión a malignidad de lesiones de alto grado se recomienda un tratamiento conservador. Una de las razones comunes relacionadas con la persistencia de infección por el VPH es el virus de inmunodeficiencia humana. Por otra parte, el adenocarcinoma in situ es un trastorno raro, no bien identificado en muestras citológicas o de inspección colposcópica; el diagnóstico se

  17. Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva.

    Science.gov (United States)

    Rakislova, Natalia; Alemany, Laia; Clavero, Omar; Del Pino, Marta; Saco, Adela; Quirós, Beatriz; Lloveras, Belen; Alejo, Maria; Halec, Gordana; Quint, Wim; de Sanjosé, Silvia; Ordi, Jaume

    2018-06-01

    Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.

  18. Prevalência de lesões intraepiteliais em atipias de significado indeterminado em um serviço público de referência para neoplasias cervicais Prevalencia de lesiones intraepiteliales en atipias de significado indeterminado en un servicio público de referencia para neoplasias cervicales Prevalence of atypical squamous cell intraepithelial lesions of undetermined significance in a public health referral service for cervical cancer

    Directory of Open Access Journals (Sweden)

    Railda Fraga Costa

    2011-01-01

    óstico colpocitológico de atipias de significado indeterminado (ASCUS fue del 23,7%, el aumento del riesgo fue directamente proporcional al de la edad y hubo mayor prevalencia de lesión intraepitelial de bajo grado, asociada a la infección por el Papilomavirus humano.OBJECTIVE: To determine the prevalence of low and high grade intraepithelial lesions in women with Pap smear diagnosis of atypical squamous cells of undetermined significance, in the city of Maceió, Alagoas. Knowing the influence of age and the etiological agents for sexually transmitted diseases on the risk of developing low and high grade intraepithelial lesions. METHODS: Cross sectional prevalence study at a public referral center for cervical cancer. We studied records of 253 women with atypical diagnoses of undetermined significance, in 2007. RESULTS: The prevalence of intraepithelial lesions was 23.7%; 26.7% were low grade and 73.3% high grade. CONCLUSIONS: The prevalence of high-grade intraepithelial lesions in women with Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS was 23.7%; the increase in risk was directly proportional to the age and higher prevalence of low grade squamous intraepithelial lesion associated with papillomavirus infection.

  19. Cryotherapy for Intra- and Perianal High-Grade Squamous Intraepithelial Lesions in HIV-Positive Men who have Sex with Men

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, Matthijs L.; Gosens, Karien C. M.; Prins, Jan M.; de Vries, Henry J. C.

    2018-01-01

    Background Available treatment options for anal high-grade squamous intraepithelial lesions (HSIL) in HIV-positive men who have sex with men (MSM) are limited by low response rates and frequent recurrences. Cryotherapy is an established therapeutic option for several pre-malignant skin disorders.

  20. Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix

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    Gupta Ruchi

    2010-01-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12. Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20. There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20% showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001. Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

  1. Prevalence of Specific Types of Human Papiloma Virus in Cervical Intraepithelial Lesions and Cervical Cancer in Macedonian Women

    Science.gov (United States)

    Aleksioska-Papestiev, Irena; Chibisheva, Vesna; Micevska, Megi; Dimitrov, Goran

    2018-01-01

    Introduction Cervical cancer is a malignancy originating in the transformation zone of the cervix, most commonly in the squamous cells. It is the fourth most common cancer in women worldwide, and the third most common cause of female cancer death. Genital human papilloma viruses (HPV) are sexually transmitted and approximately 630 milion people worldwide are infected. More than 200 genotypes, subtypes and variants have been reported, 13-15 being oncogenic type, which could be responsible for cervical intraepithelial lesions (CIN) or cancer. Aim Aim of this study was to evaluate the prevalence of this infection and to identify specific types of human papiloma virus in cervical intraepithelial lesions and cervical cancer in Macedonian women. Material and methods The study was conducted at the University Clinic for Obstetrics and Gynecology, Skopje, Macedonia, in a period of four years. The study was performed on a cohort of 1895, 18 - 73 year old patients who during primary examination had already abnormal PAP smear test. Cervical cells were collected in the lithotomy gynecological position of the patient, using endocervical cytobrush and cotton-tipped swab, and both were placed in sterile test tube with phosphate buffered saline. Samples were stored at temperature of 2 - 8 °C and Human Pappiloma Virus (HPV) genotyping was analyzed within 7 days by multiple Polymerase Chain Reaction (PCR) methods. Results The mean age of enrolled women was 40,8 years±10.36 SD(minimum of 18 and maximum 73 years. Among the patients, the presence of HPV by using PCR was detected in 40,68 % (769 patients) and was highly associated with cervical abnormalities. The prevalence of HPV was highest (82,1%) in women aged 20-years or less and it decreased with age and was lowest (19,9%) among patients older than 50 years. The prevalence of oncogenic types of the virus was higher if the cytologic diagnosis is CIN 3/Carcinoma in situ (CIS). In these patients detection of high risk HPV was in 79

  2. Colposcopic characteristics and Lugol׳s staining differentiate anal high-grade and low-grade squamous intraepithelial lesions during high resolution anoscopy

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    Naomi Jay

    2015-12-01

    Full Text Available Background: Anal squamous intraepithelial lesions (SIL and cancers are increased in immunocompromised populations. Based upon anatomic and histologic similarities, the cervix is used as the model for anal screening. During cervical colposcopy, acetic acid (AA and Lugol׳s staining (LS result in characteristic changes that help distinguish low-grade (LSIL from high-grade (HSIL. Lesion characteristics were evaluated for their ability to distinguish anal (aLSIL from anal (aHSIL during high-resolution anoscopy after application of AA and LS. Methods: AA-stained lesions were described using standard cervical colposcopic criteria. LS was then applied and lesions were characterized as Lugol׳s-negative (L−, Lugol׳s-partial (L+/−, or Lugol׳s positive (L+ and then biopsied. Biopsies were characterized as benign, squamous atypia, LSIL or HSIL. Results: 835 anal lesions were analyzed. Sensitivity and positive predictive value (PPV for aHSIL were highest for characteristics associated with cervical (cHSIL. L− was independently associated with aHSIL (OR=4.7, 95% CI=3.4–6.7. In multiple logistic regression analysis, significant predictors of aHSIL were flat contour (OR=2.24, 95% CI=1.3–3.8, mosaic pattern (OR=2.0, 95% CI=1.4–2.9, vascular punctation (OR=1.5, 95% CI=1.1–2.1 and L− (OR=2.3, 95% CI=1.5–3.4. L− staining improved the PPV of aHSIL almost twofold in lesions that otherwise had a colposcopic impression of LSIL. Conclusions: Evaluating acetowhite lesions for contour, surface, vascularity, and LS may maximize the likelihood of identifying aHSIL. Keywords: Anal, HSIL, High resolution anoscopy, Lugol׳s staining

  3. Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

    Science.gov (United States)

    Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

    2011-06-01

    Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

    Science.gov (United States)

    Wang, Zhen-Ming

    2014-01-01

    This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

  5. Management of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions of the uterine cervix with human papilloma virus infection among young women aged less than 25 years.

    Science.gov (United States)

    Ryu, Ki-Jin; Lee, Sanghoon; Min, Kyung-Jin; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan; Lee, Nak Woo

    2016-12-01

    Current ASCCP guidelines recommend repeat cytology 12 months after HPV-positive results in women aged 21-24 years with either atypical squamous cells of undetermined significance (ASCUS) or a low-grade squamous intraepithelial lesion (LSIL). The purpose of this study was to validate an algorithm in such women with ASCUS or LSIL. A multicenter cross-sectional study was carried out at three academic hospitals involving 40,847 Korean women who underwent cervical cancer screening with cytology and HPV testing with or without subsequent colposcopic biopsies between January 2007 and December 2013. Among a total of 3,193 women with available histopathology data, 762 women with ASCUS and 758 with LSIL were HPV-positive. Among HPV-positive women with ASCUS, 38.5% of women aged 21-24 years had ≥CIN2, compared to 20.8% of women aged 30-65 years and 21.1% of the total women. Among HPV-positive women with LSIL, 25.8% aged 21-24 years had ≥CIN2, compared to 21.2% of women aged 30-65 years and 21.9% of the total women. In HPV-positive women with ASCUS/LSIL aged less than 25 years, the prevalence of ≥CIN2 lesions was 34.5%, which was significantly higher than that (21.0%) in women aged ≥25 years. The risk of ≥CIN2 lesions in HPV-positive Korean women aged 21-24 years with ASCUS or LSIL was not lower than that in older women. Colposcopic examination should be considered for management of HPV-positive young women with ASCUS or LSIL. Diagn. Cytopathol. 2016;44:959-963. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Svahn, Malene F; Munk, C; Jensen, S M

    2016-01-01

    OBJECTIVE: Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited. METHODS: We established a nationwide...

  7. Variantes de lesões intra-epiteliais escamosas: relato de quatro casos Variants of intraepithelial squamous lesions: report of four cases

    Directory of Open Access Journals (Sweden)

    Álvaro P. Pinto

    2005-04-01

    Full Text Available Entre a rotina de biópsias e produtos cirúrgicos provenientes do colo uterino, um número significativo de lesões intra-epiteliais escamosas (LIE pode causar dificuldade quanto a caracterização e graduação histológica. Tais lesões têm sido identificadas e descritas isoladamente por artigos científicos como variantes histológicas de LIE cervicais. São elas a metaplasia papilar imatura atípica (MPIA e as variantes de neoplasia intra-epitelial cervical graus II/III: queratinizante, com padrão metaplásico imaturo de crescimento e escamomucinosa. Neste artigo são exemplificados quatro casos representativos das entidades citadas acima, provenientes das rotinas do Programa de Prevenção do Câncer Ginecológico do Estado do Paraná e de um laboratório privado especializado em patologia ginecológica de Curitiba, o Laboratório de Citopatologia e Anatomia Patológica Annalab. Os principais critérios diagnósticos são descritos, assim como a correlação citológica e molecular relacionada à presença e à localização do ácido nucleico viral (papilomavírus humano [HPV] nas lesões.In routine basis, among biopsies and surgical specimens derived from uterine cervix, a significant number of squamous intraepithelial lesions (SIL may be difficult to diagnose and grade. Some of these lesions were identified, isolated and reported in scientific articles as histological variants of SIL. They are: metaplastic papillary immature atypia (MPIA and the following grade II/III cervical intraepithelial neoplasia variants: keratinized, immature metaplastic-like proliferation and mucin-producing. In this article four cases representative of these variants are described. They were retrieved from the routines of a large scale gynecological cancer screening program and a private laboratory specialized on gynecological pathology, both from Paraná State, Brazil. The main histological criteria for diagnosis are described, as well cytological and

  8. Hybrid capture 2 viral load and the 2-year cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer.

    Science.gov (United States)

    Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M

    2004-11-01

    The purpose of this study was to determine the clinical value of a semiquantitative measure of human papillomavirus viral load by the hybrid capture 2 assay for stratification of the risk of histologic cervical intraepithelial neoplasia grade 3 or carcinoma. The Atypical Cells of Unknown Significance and Low-Grade Squamous Intraepithelial Lesions Triage Study was a randomized clinical trial of 5060 women with 2 years of follow-up to evaluate treatment strategies for women with equivocal or mildly abnormal cervical cytologic condition. The usefulness of the continuous hybrid capture 2 output relative light units/positive controls that were above the positive threshold (1.0 relative light units/positive controls), which was a surrogate for human papillomavirus viral load, for distinguishing between hybrid capture 2 positive women who were diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma during the study from those who were not diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma was examined with the use of receiver-operator characteristic analyses. Relative light units/positive controls values did not further discriminate between hybrid capture 2 positive women with cervical intraepithelial neoplasia grade 3 or carcinoma from those with less than cervical intraepithelial neoplasia grade 3 or carcinoma. The use of a cervical intraepithelial neoplasia grade 2 or more severe or carcinoma case definition did not alter our findings. Among women with atypical cells of unknown significance or low-grade squamous intraepithelial lesion cervical cytologic findings, the hybrid capture 2 viral load measurement did not improve the detection of 2-year cumulative cases of cervical intraepithelial neoplasia grade 3 or carcinoma significantly.

  9. The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high-risk male patients.

    Science.gov (United States)

    Greebon, Leslie J; Avery, Diane L; Prihoda, Thomas J; Valente, Philip T; Policarpio-Nicolas, Maria Luisa C

    2014-06-01

    While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high-risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin-prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co-factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission. Copyright © 2014 Wiley Periodicals, Inc.

  10. High-grade squamous intraepithelial lesion (HSIL) of the cervix with bizarre cytological appearances ('pleomorphic HSIL'): a review of 19 cases.

    Science.gov (United States)

    Stewart, Colin J R

    2017-08-01

    Cervical high-grade squamous intraepithelial lesions (HSILs) are typically characterised by a proliferation of immature basaloid cells with relatively uniform hyperchromatic nuclei. In this report we describe 19 cases of HSIL exhibiting focal but very marked nuclear atypia often associated with multinucleation ('pleomorphic HSIL'). The bizarre cytological changes mainly involved the basal epithelium particularly in endocervical crypts where the neoplastic cells undermined the native glandular epithelial cells. Superficially invasive squamous cell carcinoma (SISCCA) was present in three cases (16%) and while this was more common than in a comparative series of 40 'conventional' HSIL excision specimens (5%), the difference was not statistically significant. All three invasive cases demonstrated additional histological features that have been associated with increased risk of SISCAA (expansile crypt involvement by HSIL, luminal necrosis, and/or intraepithelial squamous maturation), and the invasive foci were associated microanatomically with conventional-type rather than pleomorphic HSIL. The bizarre cells expressed p16 and p63 proteins but usually lacked mitotic activity and showed less Ki-67 labelling than adjacent conventional HSIL. These findings suggest that pleomorphic epithelial changes in HSIL do not necessarily indicate more aggressive biological behaviour and may, in some cases, represent a degenerative phenomenon. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  11. EVALUATION OF P16INK4A PROTEIN AS A BIOMARKER FOR CERVICAL INTRAEPITHELIAL NEOPLASIA AND SQUAMOUS CELL CARCINOMA OF THE UTERINE CERVIX

    Directory of Open Access Journals (Sweden)

    Biljana Đorđević

    2011-06-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well known. Interaction of HPV proteins with cellular regulatory proteins leads to up regulation of p16INK4A. The aim of this study was to evaluate p16INK4A protein as a biomarker for CIN lesions and squamous cell carcinoma on biopsy specimens of patients who underwent biopsy of the uterine cervix due to abnormal cytological finding.The authors analyzed biopsies from 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix. Expression of p16INK4A in CIN and invasive squamous cell carcinoma was immunohistochemically analyzed by using monoclonal anti-p16INK4A antibody.A total of 50 patients with CIN and invasive squamous cell carcinoma of the uterine cervix (mean age 40.2±11.5 years, range 20-74 years were analyzed. CIN I lesions were found in 27 (54%, CIN II/CIN III lesions in 9 (18%, and invasive squamous cell carcinoma in 14 (28% patients. Differences in the expression of p16INK4A between CIN I, CIN II/CIN III and squamous cell carcinoma were statistically significant (p<0.0001. Expression of p16INK4A showed low sensitivity (7%, specificity (8%, positive predictive value (8%, and negative predictive value (7% for CIN I. Sensitivity, specificity, positive predictive value, and negative predictive value of p16INK4A were 78%, 61%, 30%, and 93% for CIN II/CIN III, and 100%, 75%, 61%, and 100% for squamous cell carcinoma, respectively.Results of this study suggest that p16INK4A protein may be a sensitive biomarker for CIN II/CIN III lesions and invasive squamous cell carcinoma of the uterine cervix.

  12. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Helmerhorst, Theo; Habbema, Dik

    2012-01-01

    To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result....

  13. Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

    Science.gov (United States)

    Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

    2009-05-01

    A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

  14. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

    DEFF Research Database (Denmark)

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf

    2013-01-01

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination...... on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical...... higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both...

  15. Clinical performance of a human papillomavirus messenger RNA test (Aptima HPV Assay) on residual material from archived 3-year-old PreservCyt samples with low-grade squamous intraepithelial lesion

    DEFF Research Database (Denmark)

    Waldstrøm, Marianne; Ornskov, Dorthe

    2011-01-01

    Human papillomavirus (HPV) testing is widely used in the triage of women with a borderline smear result but the efficiency of testing women with low-grade squamous intraepithelial lesion (LSIL) is less clear, mainly because of lack of specificity. New HPV tests are emerging, which detect E6/E7...

  16. Verrucous Squamous Cell Cancer in the Esophagus

    DEFF Research Database (Denmark)

    Egeland, C; Achiam, M P; Federspiel, B

    2016-01-01

    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic...... examinations showed a similar wart-like, white, irregular mucosa in both cases. The diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy. This cancer type has a relatively good prognosis when the diagnosis is finally obtained. Both our patients presented...

  17. HPV infection, anal intra-epithelial neoplasia (AIN and anal cancer: current issues

    Directory of Open Access Journals (Sweden)

    Stanley Margaret A

    2012-09-01

    Full Text Available Abstract Background Human papillomavirus (HPV is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM and HIV + groups. HIV + MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences. Discussion There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV + women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia, when compared to cervical cancer and CIN (cervical intraepithelial neoplasia. This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups. Summary There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer.

  18. Syndemic synergy of HPV and other sexually transmitted pathogens in the development of high-grade anal squamous intraepithelial lesions

    Directory of Open Access Journals (Sweden)

    Jenny C. McCloskey

    2017-12-01

    Full Text Available Background: Anal intraepithelial neoplasia is associated with high-risk human papillomavirus (hrHPV as a precursor to anal cancer. However, factors other than hrHPV are likely to be involved and further study of cofactors is required because of the possibility of syndemic interactions. Methods: Three hundred and fourteen patients underwent 457 operations. Histopathology and hrHPV testing using the Digene Hybrid Capture 2 (HC 2 method were performed. Demographic factors and sexually transmissible infections (STIs were recorded. Results: Results showed that hrHPV alone was associated with HSIL (OR = 4.65, p < 0.001. None of the other STIs were alone associated with HSIL but amplification of risk was found when hrHPV infection occurred with HIV (OR = 11.1; syphilis (OR = 5.58; HSV 2 (OR = 7.85; gonorrhoea (OR = 6.45 and some other infections. Conclusions: These results suggest that hrHPV is a sufficient cause of anal HSIL. Seropositivity for HIV, HSV 2, T. pallidum, HBV and HCV and a history of gonorrhoea or chlamydia exert a powerful amplifying factor increasing the risk of HSIL above the risk with hrHPV alone. Other co-factors which are associated with an increased risk of HSIL are increased age, male gender, MSM behaviour and self-reported history of more than 50 sexual partners. This pattern of disease in patients with warts is characteristic of a syndemic with potential serious increased risk of anal carcinoma. Keywords: HSIL, Anal warts, Sexually transmissible infections, High-risk HPV, HIV, Syndemic

  19. Local advanced transitional cell cancer and squamous cell cancer of ...

    African Journals Online (AJOL)

    Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was ...

  20. Age trends in the prevalence of cervical squamous intraepithelial lesions among HIV-positive women in Cameroon: a cross-sectional study

    LENUS (Irish Health Repository)

    Atashili, Julius

    2012-10-29

    AbstractBackgroundCervical squamous intra-epithelial lesions (SIL) are more frequent in HIV-positive women overall. However the appropriate age at which to begin and end cervical cancer screening for early detection of lesions in HIV-positive women is not clear. We assessed the age-specific prevalence of any SIL and SIL requiring colposcopy in HIV-positive women in Cameroon.MethodsWe enrolled, interviewed and conducted conventional cervical cytology in 282 women, aged 19--68 years, initiating antiretroviral therapy in three clinics in Cameroon. In bivariable analyses, the crude relationship between age and the presence of lesions was assessed using locally weighted regression (LOWESS) methods. In multivariate analyses, generalized linear models with prevalence as the outcome, an identity link and a binomial distribution, were used to estimate prevalence differences. Bias analyses were conducted to assess the potential effect of inaccuracies in cytology.ResultsSIL were detected in 43.5% of the 276 women with satisfactory samples, 17.8% of whom had ASC-H\\/HSIL. On average, women aged 26 to 59 tended to have a slightly higher prevalence of any SIL than other women (Prevalence difference PD: 6.5%; 95%CI: -11.4, 24.4%). This PD was a function of CD4 count (heterogeneity test p-value =0.09): amongst patients with CD4 counts less than 200cells\\/uL, the prevalence was higher in patients aged 26--59, while there was essentially no difference amongst women with CD4 counts greater than 200 cells\\/uL. ASC-H\\/HSIL were present in women as young as 19 and as old as 62. Overall the prevalence of ASC-H\\/HSIL increased by 0.7% (95%CI: -3.8%, 5.1%) per decade increase in age.ConclusionBoth severe and less severe lesions were prevalent at all ages suggesting little utility of age-targeted screening among HIV-positive women. Nevertheless, the long-term evolution of these lesions needs to be assessed in prospective studies.

  1. A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a Possible Cell of Origin.

    Science.gov (United States)

    Hong, Soon Auck; Yoo, Su Hyun; Choi, Jene; Robboy, Stanley J; Kim, Kyu-Rae

    2018-04-13

    - Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papilloma virus (LR-HPV). - To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. - A total of 26 PIM cases were evaluated by p16 INK4a , cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papilloma virus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR. - Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the 26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or 42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%) with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but p16 INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%) of which showed direct continuity. Identical HPV subtypes were confirmed in separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24, 92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7 (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases of low-grade squamous intraepithelial lesion (LSIL) were negative for both markers. - Our results suggest that PIM is a distinct subset of LSIL showing a productive HPV infection, but PIM involves the transformation zone and is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.

  2. Using gene expression in patients with endometrial intraepithelial neoplasia to assess the risk of cancer

    Directory of Open Access Journals (Sweden)

    Koah Vierkoetter

    2018-05-01

    Full Text Available Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78 in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy. Keywords: Endometrial intraepithelial neoplasia, Endometrial cancer, Gene expression, PTEN, ARID1A, Mismatch repair genes

  3. Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2006-11-01

    Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

  4. “Low-grade squamous intraepithelial lesion, cannot exclude high-grade:” TBS says “Don't Use It!” should I really stop it?

    Directory of Open Access Journals (Sweden)

    Jeanine M Chiaffarano

    2017-01-01

    Full Text Available Background: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs. Occasionally, Papanicolaou (Pap tests with evident low-grade SIL (LSIL also have some features suggestive but not diagnostic of high-grade SIL (HSIL. This study reviews our experience with “Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade” (LSIL-H and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. Methods: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. Results: There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+ was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs, cannot rule out HSIL (ASC-H, and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000 and ASC-H (P = 0.04. If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000. Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000. Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. Conclusions: “LSIL-H” category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy

  5. Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji.

    Science.gov (United States)

    Tabrizi, Sepehr N; Law, Irwin; Buadromo, Eka; Stevens, Matthew P; Fong, James; Samuela, Josaia; Patel, Mahomed; Mulholland, E Kim; Russell, Fiona M; Garland, Suzanne M

    2011-09-01

    There is currently limited information about human papillomavirus (HPV) genotype distribution in women in the South Pacific region. This study's objective was to determine HPV genotypes present in cervical cancer (CC) and precancers (cervical intraepithelial lesion (CIN) 3) in Fiji. Cross-sectional analysis evaluated archival CC and CIN3 biopsy samples from 296 women of Melanesian Fijian ethnicity (n=182, 61.5%) and Indo-Fijian ethnicity (n=114, 38.5%). HPV genotypes were evaluated using the INNO-LiPA assay in archival samples from CC (n=174) and CIN3 (n=122) among women in Fiji over a 5-year period from 2003 to 2007. Overall, 99% of the specimens tested were HPV DNA-positive for high-risk genotypes, with detection rates of 100%, 97.4% and 100% in CIN3, squamous cell carcinoma (SCC) and adenosquamous carcinoma biopsies, respectively. Genotypes 16 and 18 were the most common (77%), followed by HPV 31 (4.3%). Genotype HPV 16 was the most common identified (59%) in CIN3 specimens, followed by HPV 31 (9%) and HPV 52 (6.6%). Multiple genotypes were detected in 12.5-33.3% of specimens, depending on the pathology. These results indicated that the two most prevalent CC-associated HPV genotypes in Fiji parallel those described in other regions worldwide, with genotype variations thereafter. These data suggest that the currently available bivalent and quadrivalent HPV vaccines could potentially reduce cervical cancers in Fiji by over 80% and reduce precancers by at least 60%.

  6. Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

    Science.gov (United States)

    Kuroki, Lindsay M; Frolova, Antonina I; Wu, Ningying; Liu, Jingxia; Powell, Matthew; Thaker, Premal H; Massad, L Stewart

    2017-07-01

    The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

  7. Loop electrosurgical excision procedure in Greek patients with vaginal intraepithelial neoplasia and history of cervical cancer.

    Science.gov (United States)

    Terzakis, E; Androutsopoulos, G; Zygouris, D; Grigoriadis, C; Arnogiannaki, N

    2011-01-01

    The aim of our study was to evaluate the therapeutic effectiveness of loop electrosurgical excision procedure (LEEP) in Greek patients with vaginal intraepithelial neoplasia (VAIN) and history of cervical cancer. Between January 2002 and January 2009, eight women with histologically confirmed VAIN and history of cervical cancer were included in our study. For the LEEP procedure we used a high frequency Electrosurgery Unit with at least 80 W output. Complete response rate, at 12 months of follow-up, was 75%. Recurrence rate, at 12 months of follow-up, was 25%. Complete response rate, at 24 months of follow up, was 62.5%. Recurrence rate, at 24 months of follow up, was 37.5%. LEEP may constitute a valuable excisional method for the treatment of VAIN in cases with a history of cervical cancer. It provides an interpretable specimen of the whole lesion within a few minutes. It needs a short period of training and has low cost.

  8. Oesophageal squamous cell cancer in a South African tertiary hospital

    African Journals Online (AJOL)

    The site of tumour location was in the middle 96 (60.4%), distal 42(26.4%) and proximal 17(10.6%) oesophagus. The male to female ratio was 1:1 ... with HIV negative patients. Key words: Oesophageal cancer, squamous cell cancer, HIV, dental hygiene, socioeconomic status, South Africa, esophageal cancer, risk factors ...

  9. Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Munk, Christian; Jensen, Signe Marie

    2016-01-01

    Background: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal...

  10. Human Papilloma Virus 16 and 18 Association in Cervical Intraepithelial Lesions and Cervical Cancers by In Situ Hybridization

    Directory of Open Access Journals (Sweden)

    Mohanty Manisa

    2017-03-01

    Full Text Available Objective: To correlate the association of high risk Human Papilloma Virus (HPV 16, 18 in cervical intraepithelial lesions and cervical cancers by in-situ hybridization (ISH technique. Study Group: Cervical biopsy and hysterectomy specimen of 78 young and adult women, attending Hi-Tech Medical College and Hospital, Bhubaneswar, who were clinically or cytologically suspected of cervical intraepithelial lesion or cervical cancer were taken as source of target viral DNA. Material: Formalin 10% as fixative H & E stain as routine staining agent In-situ hybridization kit for HPV 16 and 18 DNA. Method: After following standard protocol for surgical grossing, HPV 16, 18 In-situ hybridization kit was used on paraffin embedded tissue sections. Results: The percentage of positive cases was highest in cervical cancer patients followed by cervical intraepithelial lesions, high grade, and low grade. Conclusion: This study has been carried out for the first in our state and our results show high degree of positivity of HPV 16/18 in females with cervical intraepithelial lesions and cervical cancers attending our tertiary care hospital.

  11. Metastatic Squamous Neck Cancer with Occult Primary Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Metastatic squamous neck cancer with occult primary treatment options include surgery, radiation therapy or a combination of both. Get detailed information about newly diagnosed or recurrent metastatic squamous neck cancer in this summary for clinicians.

  12. Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+ using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US in Catalonia, Spain

    Directory of Open Access Journals (Sweden)

    Ibáñez Raquel

    2012-01-01

    Full Text Available Abstract Background A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US. HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+ in women with a cytological diagnosis of ASC-US. Methods During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Results Among the 611 women diagnosed with ASC-US, 493 (80.7% had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years. hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI = 85.5-99.9 and specificity was 68.3% (95%CI

  13. Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

    Science.gov (United States)

    Ibáñez, Raquel; Moreno-Crespi, Judit; Sardà, Montserrat; Autonell, Josefina; Fibla, Montserrat; Gutiérrez, Cristina; Lloveras, Belen; Alejo, María; Català, Isabel; Alameda, Francesc; Casas, Miquel; Bosch, F Xavier; de Sanjosé, Silvia

    2012-01-26

    A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US. During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2

  14. HPV infection and intraepithelial lesions from the anal region: how to diagnose?

    Directory of Open Access Journals (Sweden)

    Newton Sérgio de Carvalho

    Full Text Available In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.

  15. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

    Directory of Open Access Journals (Sweden)

    Monica Molano

    Full Text Available Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC are associated with human papillomavirus (HPV. Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS and laser capture microdissected (LCM tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

  16. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    Science.gov (United States)

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  17. Cetuximab And The Head And Neck Squamous Cell Cancer.

    Science.gov (United States)

    Concu, Riccardo; Cordeiro, Maria Natalia Dias Soeiro

    2018-01-12

    The head and neck squamous cell cancer (HNSCC) is the most common type of head and neck cancer (more than 90%), and all over the world more than a half million people have been developing this cancer in the last years. This type of cancer is usually marked by a poor prognosis with a really significant morbidity and mortality. Cetuximab received early favor as an exciting and promising new therapy with relatively mild side effect, and due to this received authorization in the 2004 from the European Medicines Agency (EMA) and in the 2006 from the Food and Drug Association (FDA) for the treatment of patients with squamous cell cancer of the head and neck in combination with radiation therapy for locally advanced disease. In this work we will review the application and the efficacy of the Cetuximab in the treatment of the HNSCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Ultraviolet B irradiation induces expansion of intraepithelial tumor cells in a tissue model of early cancer progression.

    Science.gov (United States)

    Mudgil, Adarsh V; Segal, Nadav; Andriani, Frank; Wang, Youai; Fusenig, Norbert E; Garlick, Jonathan A

    2003-07-01

    Ultraviolet B irradiation is thought to enable skin cancer progression as clones of genetically damaged keratinocytes escape apoptosis and expand at the expense of adjacent normal cells. Mechanisms through which potentially malignant cells in human skin undergo clonal expansion, however, are not well understood. The goal of this study was to characterize the role of ultraviolet B irradiation on the intraepithelial expansion of early stage human tumor cells in organotypic skin cultures. To accomplish this, we have studied the effect of ultraviolet B irradiation on organotypic cultures that were fabricated by mixing normal human keratinocytes with beta-galactosidase-marked, intraepithelial tumor cells (HaCaT-ras, clone II-4), which bear mutations in both p53 alleles and harbor an activated H-ras oncogene. We found that when organotypic mixtures were exposed to an ultraviolet B dose of 50 mJ per cm2, intraepithelial tumor cells underwent a significant degree of proliferative expansion compared to nonirradiated cultures. To understand this response, organotypic cultures of nor-mal keratinocytes were exposed to ultraviolet B and showed a dose-dependent increase in numbers of sunburn cells and TUNEL-positive cells although their proliferation was suppressed. In contrast, neither the apoptotic nor the proliferative response of II-4 cells was altered by ultraviolet B in organotypic cultures. The differential response of these cell types suggested that II-4 cells were resistant to ultraviolet-B-induced alterations, which allowed these intraepithelial tumor cells to gain a selective growth and survival advantage relative to neighboring normal cells. These findings demonstrate that ultraviolet B exposure can induce the intraepithelial expansion of apoptosis-resistant, p53-mutant, and ras-activated keratinocytes, suggesting that this agent can act to promote the early stages of epithelial carcinogenesis.

  19. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.

    Science.gov (United States)

    Bostwick, D G; Alexander, E E; Singh, R; Shan, A; Qian, J; Santella, R M; Oberley, L W; Yan, T; Zhong, W; Jiang, X; Oberley, T D

    2000-07-01

    Oxidative stress results in damage to cellular structures and has been linked to many diseases, including cancer. The authors sought to determine whether the expression of three major antioxidant enzymes, copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was altered in human prostate carcinoma and its likely precursor, high grade prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species damage was evaluated by measuring the expression of the DNA adduct 8-hydroxydeoxyguanosine. The authors evaluated the tissue expression of the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold electron microscopy, and enzymatic assay. The polymerase chain reaction was used to amplify and screen tissue specimens for the genes of SOD1, SOD2, and extracellular SOD (SOD3). Matched paraffin embedded tissue sections were evaluated by RNA in situ hybridization for expression of SOD1 and immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. All prostatic tissues, including cancer, displayed immunoreactivity for the three antioxidant enzymes in epithelial cells, with no staining of the stroma, inflammatory cells, or endothelial cells. The number of immunoreactive cells was greater in benign epithelium than in PIN and cancer for each enzyme. The mean percentage and intensity of immunoreactive cells was greatest for SOD2, intermediate for SOD1, and lower for catalase. Staining in cancer was heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1 labeling was invariably weaker, with nuclear labeling in benign epithelium and cytoplasmic labeling in cancer cells. There was no difference in enzyme activity for the three antioxidant enzymes between benign epithelium and cancer. No mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of SOD3, except for 3 of 20 cases with

  20. Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention.

    Science.gov (United States)

    Carlson, Joseph W; Miron, Alexander; Jarboe, Elke A; Parast, Mana M; Hirsch, Michelle S; Lee, Yonghee; Muto, Michael G; Kindelberger, David; Crum, Christopher P

    2008-09-01

    A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women. Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review. Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up. The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention.

  1. Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia.

    Directory of Open Access Journals (Sweden)

    Masakazu Sato

    Full Text Available While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology, GSE27678 (cytology and GSE75132 (cytology, a prospective study. From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer (Kruskal-Wallis test, p < 0.0001. From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer were obtained (Kruskal-Wallis test, p < 0.001. From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia.

  2. Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia: a nationwide population-based cohort study in Denmark.

    Science.gov (United States)

    Svahn, M F; Munk, C; Jensen, S M; von Buchwald, C; Frederiksen, K; Kjaer, S K

    2016-07-01

    Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited. We established a nationwide cohort of approximately 2,500,000 Danish women born in 1918-1990. By linking the cohort to population-based health registries, we obtained information on CIN3/AIS, cancer, migration, death, education, and smoking. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the association between CIN3/AIS and risk of head-and-neck squamous cell carcinoma (HNSCC). HRs were presented for any HNSCC and for four subgroups categorized by their anticipated degree of association with human papillomavirus (HPV). A history of CIN3/AIS was significantly associated with an increased overall relative risk of HNSCC after adjustment for year of birth, attained age, and length of education. The risk was especially high for sites anticipated to be strongly associated with HPV (e.g. base of tongue, tonsils) (HR, 2.49; 95% CI, 1.84-3.36). Lower risks were found for sites anticipated to be not or weakly associated with HPV (e.g. nasal cavity, middle ear, sinuses) (HR, 1.29; 95% CI, 0.61-2.76). Women with a history of CIN3/AIS have a significantly higher risk of HNSCC than women without such a history. The increased relative risk persisted for at least 20years after the CIN3/AIS diagnosis. Women with CIN3/AIS may be more susceptible to the consequences of HPV and/or may have higher risk behavior, such as smoking. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The emerging epidemic of melanoma and squamous cell skin cancer

    International Nuclear Information System (INIS)

    Glass, A.G.; Hoover, R.N.

    1989-01-01

    Squamous cell skin cancer, though common, remains largely unreported and unstudied, with little known about its incidence and time trends. The authors have used a unique resource--a continuous population-based registry of cases of squamous cell skin cancer within a single prepaid health plant--to describe basic epidemiologic features of this malignancy and compare it with the more widely studied melanoma. Both malignancies are considerably more common in this population than they expected based on previous reports from the general population. From the 1960s to the 1980s, the incidence of squamous cell skin cancer increased 2.6 times in men and 3.1 times in women, while incidence of melanoma rose 3.5-fold and 4.6-fold in men and women, respectively. Skin cancers of both types involving the head and neck or the extremities increased essentially in parallel over these 27 years. Melanomas of the trunk, however, appeared to increase at a faster rate in both sexes. These observations are consistent with the impression that the rising incidence of both malignancies may be attributable to increased voluntary exposure to the sun over an extended period

  4. Immunocytoexpression profile of ProExC in smears interpreted as ASC-US, ASC-H, and cervical intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    Zeynep Tosuner

    2017-01-01

    Full Text Available Aims: We aimed to investigate the immunocytoexpression profiles of a novel assay ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 in abnormal interpreted smears. Settings and Design: Screening programs with Papanicolaou smear and high risk group human papilloma virus testing have yielded a dramatic reduction of cervical cancer incidence. However, both of these tests have limited specificity for the detection of clinically significant cervical high grade lesions. ProEx C for topoisomerase II alpha (TOP2A and minichromosome maintenance protein 2 (MCM2 has been considered to have tight association with high grade intraepithelial lesions. Materials and Methods: A total number of 54 SurePath cervical cytology specimens of patients previously interpreted as atypical squamous cells-undetermined significance (ASC-US, atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H, low grade squamous intraepithelial lesion (LSIL, and high grade squamous intraepithelial lesion (HSIL were included in our study. Results and Conclusions: ProEx C was positive in 14 of HSILs (100%, 3 of 19 LSILs (16%, 2 of 4 ASC-Hs, and none of ASC-USs (0%. The ProEx C test showed very intense nuclear staining in all cytologically abnormal cells. Further studies are indicated to evaluate the diagnostic role of ProEx C.

  5. Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

    Science.gov (United States)

    Tai, Yi Jou; Chen, Yun Yuan; Hsu, Huang Cheng; Chiang, Chun Ju; You, San Lin; Chen, Chi An; Cheng, Wen Fang

    2018-07-01

    To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  6. Vulvær intraepithelial neoplasi

    DEFF Research Database (Denmark)

    Hansen, Signe Østergaard; Vorbeck, Christina Steen; Meinert, Mette

    2018-01-01

    Vulvar intraepithelial neoplasia Vulvar intraepithelial neoplasia (VIN) is a rare but premalig­nant condition. VIN has two aetiological pathways: a human papillomavirus (HPV)-dependent pathway, which is a vulvar high-grade squamous intraepithelial lesion (HSIL), and an HPV-independent pathway......, called differentiated VIN (d-VIN), associated with lichen sclerosus. d-VIN is more aggressive than vulvar HSIL. In case of symptoms, a biopsy should be performed. The recurrence risk is high: 25-50% regardless of treatment type. We recommend treatment with imiquimod as first choice to avoid mutilating...

  7. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  8. Long-term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3-A Danish nationwide cohort study

    DEFF Research Database (Denmark)

    Sand, Freja Laerke; Frederiksen, Kirsten; Munk, Christian

    2018-01-01

    Using nationwide Danish registries we examined the long-term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918......-1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative...... risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81-2.35). Analyses according...

  9. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  10. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium

    NARCIS (Netherlands)

    Fleshner, N.E.; Kapusta, L.; Donnelly, B.; Tanguay, S.; Chin, J.; Hersey, K.; Farley, A.; Jansz, K.; Siemens, D.R.; Trpkov, K.; Lacombe, L.; Gleave, M.; Tu, D.; Parulekar, W.R.

    2011-01-01

    PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind

  11. Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

    Science.gov (United States)

    Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

    2018-02-01

    The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

  12. Immunohistochemical characteristic of expression levels of Kі-67, p16INK4a, HPV16 in cervical intraepithelial neoplasia and cervical cancer

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2017-08-01

    Full Text Available Squamous cervical cancer (SCC is a common tumor in women, which is preceded by the series of pathological processes, among which the key role is played by cervical intraepithelial neoplasia (CIN. Aim. To study the characteristics of immunohistochemical (IHC expression of Ki-67, p16INK4a, HPV16 in squamous cervical epithelium (SCE with dysplastic changes of varying degree (CIN I–III and also in the tumor cells of SCC. Materials and methods. Pathohistological and IHC studies of uterine cervix biopsies from 53 patients (the age ranged from 18 to 45 years were performed. Results. It was found that SCE with CIN I is characterized by the low Ki-67 expression level (Me = 17.87 % (13.76, 22.44 and the extremely low p16INK4a expression level (Me = 0.00 CUOD (0.00; 29.64. The proportion of HPV16-positive patients with CIN I is 27.27 %. CIN II is characterized by the average proliferation level in SCE (Me = 44.96 % (34.91, 55.41 and the moderate p16INK4a expression level (Me = 75.71 CUOD (51.24, 82, 41. The proportion of HPV16-positive patients with CIN II is 71.43 %. CIN III is characterized by the high proliferation level (Me = 74.62 % (68.50, 84.67 and by the high p16INK4a expression level of in SCE (Me = 117.47 CUOD (95.38, 123, 93; the proportion of HPV16-positive patients with CIN III is 77.78%. In all the patients with SСС, nuclear and cytoplasmic expression of HPV16 was detected in the tumor cells. High expression levels of Ki-67 and p16INK4a were detected in the tumor cells. There are direct correlations between the expression levels of Ki-67, p16INK4a, HPV16 and CIN degree. Conclusions. These data indicate that the expression levels of Ki-67, p16INK4a and HPV16 increase with the increasing of CIN grade. The absence of statistically significant differences between the expression levels of Ki-67, p16INK4a and HPV16 in CIN III and the same levels in the tumor cells of SCC indicates that these markers cannot be used for differential diagnosis

  13. Human Papilloma Virus in Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

    2012-01-01

    Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

  14. Squamous cell lung cancer in a male with pulmonary tuberculosis.

    Science.gov (United States)

    Skowroński, Marcin; Iwanik, Katarzyna; Halicka, Anna; Barinow-Wojewódzki, Aleksander

    2015-01-01

    Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.

  15. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008

    DEFF Research Database (Denmark)

    Nielsen, Ann; Plum, Christian Edinger Munk; Kjaer, Susanne K

    2012-01-01

    The aim of the study was to determine the incidences of anal cancer and high-grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all...... anal cancers in the Danish Cancer Register in the period 1978-2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age-, period- and histology-specific incidence rates were estimated. During the 30-year period, 2187 anal cancers were identified, two thirds of which were...... in women. Between 1978-1982 and 2003-2008, the age-standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100 000 person-years in women and from 0.45 to 0.80 per 100 000 person-years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608...

  16. Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma.

    Science.gov (United States)

    Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Dodda Thimmasandra Ramanjanappa, Ravindra; Das, Debashish; Pandian, Ramanan; Khora, Samanta Sekhar; Kuriakose, Moni Abraham; Suresh, Amritha

    2017-06-01

    Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p squamous cell carcinoma origin (93.49 ± 0.47%, p squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.

  17. The clinical value of squamous cell carcinoma antigen in cancer of the uterine cervix

    NARCIS (Netherlands)

    de Bruijn, HWA; Duk, JM; van der Zee, AGJ; Pras, E; Willemse, PHB; Hollema, H; Mourits, MJE; de Vries, EGE; Aalders, JG; Boonstra, J.

    1998-01-01

    A review is given of the clinical use and interpretation of serum tumor marker levels during the treatment of patients with cancer of the uterine cervix, Pretreatment serum squamous cell carcinoma (SCC) antigen provides a new prognostic factor in early stage squamous cell carcinoma of the uterine

  18. Metastatic Squamous Neck Cancer with Occult Primary Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Metastatic squamous neck cancer with occult primary (unknown primary) treatment options include surgery, radiation therapy, or a combination of both. Learn more about the diagnosis and treatment of these tumors in this expert-reviewed summary.

  19. Perceived cervical cancer risk among women treated for high-grade cervical intraepithelial neoplasia: The importance of specific knowledge.

    Directory of Open Access Journals (Sweden)

    Sonia Andersson

    Full Text Available Women with high-grade cervical intraepithelial neoplasia (CIN are at increased risk for developing cervical cancer. We examine how women with high-grade CIN perceive their own risk, and about pertinent knowledge concerning human high-risk papillomavirus (HPV, CIN and cervical cancer.All patients who underwent first-time treatment of high-grade CIN (grade 2+ were followed-up at 6-months at the Karolinska University Hospital, Stockholm, Sweden and were invited to participate in the present study. This included completion of a questionnaire examining sociodemographic characteristics, self-perceived risk of cervical cancer without regular gynecologic follow-up, and 14 queries about HPV, CIN and cervical cancer knowledge, inter alia.The participation rate was 96.6%, with 479 women enrolled in this study. Over 75% were age 40 or younger, over half had completed university education. Most were married or co-living with their partner and were gainfully employed. On a scale scored from 10 (highest self-perceived risk of cervical cancer without regular gynecologic follow-up to 1 (lowest self-perceived risk, 64% rated their risk ≥ 7; almost 30% viewed their risk ≤ 6 and 7.5% did not rate their risk. A Specific Knowledge Scale with six of the queries explained 58.3% of the total variance. Nearly 30% of the women answered four or fewer of the six queries correctly. The Specific Knowledge Scale predicted self-perceived cervical cancer risk (Odds ratio = 11.3, 95% Confidence Interval 5.6 - 22.6 after adjusting for age, income and education. Most of the women with low self-perceived cervical cancer risk did not rate their HPV-related knowledge as good. However, 32 predominantly university-educated women, with low self-perceived cervical cancer risk, considered their HPV-related knowledge good.It is vital to effectively convey accurate information about these patients' cervical cancer risk, needed preventive and follow-up measures, together with the relevant

  20. Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.

    Science.gov (United States)

    Sánchez-Lander, Jorge; Cortiñas, Paula; Loureiro, Carmen Luisa; Pujol, Flor Helene; Medina, Francisco; Capote-Negrín, Luis; Bianchi, Gino; García-Barriola, Victoria; Ruiz-Benni, Angela; Avilán-Rovira, José; Acosta, Humberto

    2012-10-01

    This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types. HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006). this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Declining prevalence of cytological squamous intraepithelial lesions of the cervix among women living with well-controlled HIV - Most women living with HIV do not need annual PAP smear screening.

    Science.gov (United States)

    Aho, Inka; Kivelä, Pia; Haukka, Jari; Sutinen, Jussi; Heikinheimo, Oskari

    2017-11-01

    Cervical screening by means of annual Papanicolaou (PAP) smears has been recommended for all women living with HIV. We analysed the results of our annual PAP smear screening program to identify low-risk subgroups for less rigorous screening. The study comprised 369 women followed at the Helsinki University Hospital 2002-2013, with a total of 2033 PAP smear results. We analyzed the temporal changes in PAP smear findings. Logistic regression analysis for binominal dependent variables was used for assessing risk factors for ever having cytological squamous intraepithelial lesions (hereafter referred as SIL) using generalized estimating equations taking into account multiple observations of each patient. Most women had well-controlled HIV, especially towards the end of the study. PAP smear results improved substantially. At the time of each individual's last PAP smear, 90.0% of the findings displayed normal results. Conversely, the rate of SIL decreased from 16.8% to 4.6% from 2002 to 2013. In multivariate analysis the risk of SIL was significantly lower in women with consecutive normal PAP smear findings during the first two years of follow up [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.10-0.45, p 500 cells/μL (OR 0.11, 95% CI 0.05-0.26, p < 0.001). Widespread use of combination antiretroviral therapy (cART) and systematic cervical screening has reduced the rate of abnormal PAP smears. It seems feasible to identify low-risk women by combining HIV-related information and PAP smear results. Screening low-risk women living with HIV at three-year intervals similar to HIV-negative women appears justified. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  2. Risk of cervical intra-epithelial neoplasia and invasive cancer of the cervix in DES daughters

    NARCIS (Netherlands)

    H. Verloop (Herman); F.E. van Leeuwen (F.); T.J.M. Helmerhorst (Theo); I.M.C.M. de Kok (Inge); van Erp, E.J.M.; H.H. van Boven (Hester); M.A. Rookus (Matti)

    2017-01-01

    textabstractObjective: Women exposed to diethylstilbestrol in utero (DES) have an increased risk of clear cell adenocarcinoma (CCA) of the vagina and cervix, while their risk of non-CCA invasive cervical cancer is still unclear. Methods: We studied the risk of pre-cancerous (CIN) lesions and non-CCA

  3. Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Oral squamous cell carcinoma (OSCC) is a major oral cancer subtype that is the fourth most common cancer affecting Taiwanese men. Despite known risk behaviors such as cigarette smoking, alcohol drinking, and betel nut chewing often indulged by Taiwanese men, the genetic contribution to the incidence or progression of OSCC has yet been elucidated in the Taiwanese population.

  4. A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

    Science.gov (United States)

    In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to

  5. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

    Science.gov (United States)

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

  6. Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)

    International Nuclear Information System (INIS)

    Higashi, Kotaro; Takase, Shuko; Ohguchi, Manabu; Seki, Hiroyasu; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Rikimaru, Shigeho.

    1992-01-01

    This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r=-0.701, p<0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy. (author)

  7. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  8. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    Science.gov (United States)

    2017-10-09

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  9. Prevalência das lesões intra-epiteliais de alto grau em pacientes com citologia com diagnóstico persistente de ASCUS Prevalence of high-grade squamous intraepithelial lesions in patients with persistent cytological diagnosis of ASCUS

    Directory of Open Access Journals (Sweden)

    Fernanda Rangel da Veiga

    2006-02-01

    ASCUS é de cerca de 12%. Não foi possível evidenciar maior probabilidade de LIAG/câncer em qualquer das faixas etárias analisadas, porém este resultado pode ter sido limitado pelo pequeno tamanho amostral.PURPOSE: to determine the prevalence of high-grade squamous intraepithelial lesions (HSIL and cancer in women with cytological diagnosis of persistent ASCUS (atypical squamous cells of undetermined significance for 6 months in the last 7 years. We also assessed if age could be a predictive factor for presence of HSIL/cancer in this group. METHODS: we included 215 cases of non-pregnant and HIV-seronegative women with cytological diagnosis of persistent ASCUS (unespecific with at least 6 months of interval between smears. This cytological diagnosis was compared to histological diagnosis obtained by biopsy (large loop excision of the transformation zone or cone biopsies, and considered negative when colposcopy was satisfactory without lesions or, when unsatisfactory, no lesion was detected after at least one cytological and colposcopic follow-up. RESULTS: among the 215 cases, 49.3% had negative results (CI 95%: 42.6-55.9. The prevalence of histological confirmed low-grade squamous intraepithelial lesion was 38.6% (CI 95%: 32.1- 45.1 and HSIL was 10.7% (CI 95%: 6.5-14.8. Cases of cancer were found in 1.4% of patients (CI 95%: 0-2.9. We could not find a significant difference between the prevalence of HSIL/cancer according to age group using the cutoff point of 35 years. CONCLUSION: HSIL/cancer prevalence observed in this study has shown the risk of finding this kind of lesions in about 12% of women assisted in our public health system with two cytological diagnosis of ASCUS. A higher probability of HSIL/cancer in the different age groups was not found but this result was limited by our small sample size.

  10. Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube.

    Science.gov (United States)

    Yang, Junzheng; Zhou, Yilan; Ng, Shu-Kay; Huang, Kuan-Chun; Ni, Xiaoyan; Choi, Pui-Wah; Hasselblatt, Kathleen; Muto, Michael G; Welch, William R; Berkowitz, Ross S; Ng, Shu-Wing

    2017-06-17

    Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors. RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors. Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection. The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high

  11. Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

    Science.gov (United States)

    2014-01-01

    Background Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC. PMID:25048361

  12. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  13. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

    Directory of Open Access Journals (Sweden)

    K.S. Schwab

    2016-06-01

    Full Text Available Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

  14. Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, Kirsten Egebjerg; Schmiedel, Sven; Frederiksen, Kirsten

    2012-01-01

    were also conducted. Hazard ratios (HRs) for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CIs) were calculated in the 2 groups. RESULTS: Among high-risk HPV positive women......BACKGROUND: Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. METHODS: In a population-based cohort study, 8,656 women underwent a structured interview......, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n=1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection...

  15. Associations between methylation of paternally expressed gene 3 (PEG3, cervical intraepithelial neoplasia and invasive cervical cancer.

    Directory of Open Access Journals (Sweden)

    Monica D Nye

    Full Text Available Cytology-based screening for invasive cervical cancer (ICC lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR and confidence intervals (CI 95% for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1. HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6 and ICC (OR = 29.5, 95% CI 6.3-38.4. Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs methylation (r = 0.34 p<0.0001, while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047. Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC, especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with

  16. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna

    2008-01-01

    BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We...

  17. PECULIARITIES OF PROLIFERATIVE ACTIVITY OF CERVICAL SQUAMOUS CANCER IN HIV INFECTION.

    Science.gov (United States)

    Lytvynenko, M; Shkolnikov, V; Bocharova, T; Sychova, L; Gargin, V

    2017-09-01

    Patients with human immunodeficiency virus (HIV) infection have a statistically significant increased risk of developing cervical cancer. The expression of the human Ki-67 protein is strictly associated with cell proliferation. The purpose of our work was detection of proliferative activity in cervical squamous cancer in women with HIV infection. We investigated 24 cases (12 patients with HIV and 12 patients without HIV infection) of cervical carcinoma, where biopsy had been performed before the treatment. According to histopathological diagnoses, well-differentiated, moderately and poorly differentiated squamous cell carcinoma (7, 13 and 4 cases respectively) was determined. Mean age of women in the group with HIV infection was 32.7 years, and 38.2 years in the group without HIV infection. Detection of protein Ki-67 expression was performed with nuclear staining in the intermediate and superficial cells. The results of this work show that proliferative activity of cervical squamous cancer in women with HIV infection is characterized by a higher level of Ki-67 with averaging level for all histological types of squamous cell carcinoma 62.5±5.6% that is one and half times higher than in group without HIV infection. Depending on a histological type, expression of Ki-67 has increased from 4.7±3.8% in well-differentiated squamous cell carcinoma up to 89.2±5.1% in poorly differentiated squamous cell carcinoma for group with HIV, and from 21.3±2.4% to 79.4±3.7 in group without HIV.

  18. A case of squamous cell lung cancer after treating with radiation for small cell lung cancer

    International Nuclear Information System (INIS)

    Hayashi, Toshinari; Ide, Hiroshi; Siomi, Katsuhiko; Nakamura, Yukinobu; Tada, Shinya; Kageyama, Hiroshi; Kido, Masamitsu

    1999-01-01

    A 77-year-old man was admitted due to an abnormal shadow on a chest X-ray film in September 1993. Small cell lung cancer was diagnosed by transbronchial lung biopsy of left S 3 . Because of his pulmonary and renal dysfunction, he received only 40 Gy irradiation alone, and the tumor shadow disappeared. After 38 months' observation, a new nodular shadow was detected in the left upper lung field in March 1997. A tumor was found in left B 3 by bronchoscopy, and biopsy revealed squamous cell carcinoma. Because of his advanced age and hypoxia, he has had no active treatment. This was a rare case of small cell lung cancer with long term survival, treated only by radiation, in which a different histologic type of carcinoma appeared in the same radiation field. (author)

  19. Second cancers after squamous cell carcinoma and adenocarcinoma of the cervix

    DEFF Research Database (Denmark)

    Chaturvedi, Anil K; Kleinerman, Ruth A; Hildesheim, Allan

    2008-01-01

    PURPOSE: Although cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) are both caused by human papillomavirus (HPV) infection, they differ in cofactors such as cigarette smoking. We assessed whether these cofactor differences translate into differences in second cancer risk. PATIENTS...... AND METHODS: We assessed second cancer risk among 85,109 cervical SCC and 10,280 AC survivors reported to population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States. Risks compared to the general population were assessed using standardized incidence ratios (SIR). RESULTS......: Overall cancer risk was significantly increased among both cervical SCC survivors (n = 10,559 second cancers; SIR, 1.31; 95% CI, 1.29 to 1.34) and AC survivors (n = 920 second cancers; SIR, 1.29; 95% CI, 1.22 to 1.38). Risks of HPV-related and radiation-related cancers were increased to a similar extent...

  20. FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

    Science.gov (United States)

    Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

    2018-01-01

    The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

  1. Oesophageal squamous cell cancer in a South African tertiary hospital

    African Journals Online (AJOL)

    Background. Oesophageal cancer is the eighth most common cancer .... patients from the entire eastern seaboard of South Africa. Patients ... a school graduate and a household income of more than R10 .... (p = 0.63); however a significant difference in dental care .... Coping with esophageal cancer approaches worldwide.

  2. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  3. Anal intraepithelial neoplasia in HIV+ men

    NARCIS (Netherlands)

    Richel, O.

    2014-01-01

    In this thesis we investigated several aspects of anal intraepithelial neoplasia (AIN) in HIV+ men who have sex with men (MSM). This condition has gained clinical interest because of the impressive increase of the anal cancer incidence in HIV+ MSM since the introduction of combination antiretroviral

  4. Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

    Science.gov (United States)

    Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

    2017-10-01

    The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link.

    Science.gov (United States)

    Bozinovski, Steven; Vlahos, Ross; Anthony, Desiree; McQualter, Jonathan; Anderson, Gary; Irving, Louis; Steinfort, Daniel

    2016-02-01

    Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour-promoting serum amyloid A (SAA) and IL-17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD-lung cancer overlap. © 2015 The British Pharmacological Society.

  6. Epidermal Growth Factor Receptor Activating Mutations in Squamous Histology of Lung Cancer Patients of Southern Bulgaria

    Directory of Open Access Journals (Sweden)

    Genova Silvia N.

    2015-12-01

    Full Text Available There is only limited data on the prevalence of epidermal growth factor receptor (EGFR activating mutations in squamous cell carcinomas and adenosquamous carcinomas of the lung in patients of the Southern Bulgarian region and the efficacy of EGFR tyrosine kinase inhibitors. AIM: Previous reports for Bulgarian population showed high incidence of EGFR mutations in the squamous cell carcinomas, so we set the goal to investigate their frequency in Southern Bulgaria, after precise immunohistochemical verification of lung cancers. MATERIALS AND METHODS: Two hundred and thirty-six lung carcinomas were included in this prospective study. All biopsies were initially analysed with p63, TTF1, Napsin A, CK7, CK34βE12, synaptophysin, CK20 and CDX2. Two hundred and twenty-five non-small cell lung carcinomas were studied with real-time PCR technology to assess the status of the EGFR gene. RESULTS: We detected 132 adenocarcinomas (58.7%, 89 squamous cell carcinomas (39.2%, 4 adenosquamous carcinomas (1.8%, 9 large cell neuroendocrine carcinomas (3.8% and 2 metastatic colorectal adenocarcinomas (0.8%. Activating mutations in the EGF receptor had 3 out of 89 squamous cell carcinomas (3.37%. We have established mutations in L858R, deletion in exon 19 and rare mutation in S7681. One out of four adenosquamous carcinomas had a point mutation in the L858R (25%. CONCLUSIONS: The frequency of EGFR mutations we found in lung squamous cell carcinomas in a Southern Bulgarian region is lower than that in European countries. Ethnic diversity in the region does not play role of an independent predictive factor in terms of mutation frequency.

  7. Squamous cell carcinoma - invasive (image)

    Science.gov (United States)

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  8. Metastatic squamous cell non-small-cell lung cancer (NSCLC: disrupting the drug treatment paradigm with immunotherapies

    Directory of Open Access Journals (Sweden)

    Sarah L Scarpace

    2015-10-01

    Full Text Available Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR and anaplastic lymphoma kinase (ALK mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1 or its ligand (PD-L1 (nivolumab and pembrolizumab have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

  9. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    Science.gov (United States)

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  10. The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Lucio Dell'Atti

    Full Text Available ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa after a high-grade prostatic intraepithelial neoplasia (HGPIN diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4% patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001, Gleason score distribution (p<0.001, and number of positive biopsy cores (p<0.002 between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001. Moreover, increasing duration of metformin assumption (≥2 years was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

  11. World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer.

    Science.gov (United States)

    Santesso, Nancy; Mustafa, Reem A; Schünemann, Holger J; Arbyn, Marc; Blumenthal, Paul D; Cain, Joanna; Chirenje, Michael; Denny, Lynette; De Vuyst, Hugo; Eckert, Linda O'Neal; Forhan, Sara E; Franco, Eduardo L; Gage, Julia C; Garcia, Francisco; Herrero, Rolando; Jeronimo, José; Lu, Enriquito R; Luciani, Silvana; Quek, Swee Chong; Sankaranarayanan, Rengaswamy; Tsu, Vivien; Broutet, Nathalie

    2016-03-01

    It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries. Copyright © 2015. Published by Elsevier Ireland Ltd.

  12. Detection of Human Papillomavirus Infection in Patients with Vaginal Intraepithelial Neoplasia.

    Science.gov (United States)

    Lamos, Cristina; Mihaljevic, Charlotte; Aulmann, Sebastian; Bruckner, Thomas; Domschke, Christoph; Wallwiener, Markus; Paringer, Carmen; Fluhr, Herbert; Schott, Sarah; Dinkic, Christine; Brucker, Janina; Golatta, Michael; Gensthaler, Lisa; Eichbaum, Michael; Sohn, Christof; Rom, Joachim

    2016-01-01

    Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions. 67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System). All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL

  13. Cervical cancer screening and treatment of cervical intraepithelial neoplasia in female sex workers using “screen and treat” approach

    Directory of Open Access Journals (Sweden)

    Joshi S

    2015-05-01

    Full Text Available Smita Joshi,1 Vinay Kulkarni,2 Trupti Darak,2 Uma Mahajan,1 Yogesh Srivastava,3 Sanjay Gupta,3 Sumitra Krishnan,1 Mahesh Mandolkar,2 Alok Chandra Bharti31Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI, Jehangir Hospital Premises, Pune, Maharashtra, India; 2Prayas Health Group, Amrita Clinic, Pune, India; 3Institute for Cytology and Preventive Oncology, Indian Council of Medical Research, New Delhi, IndiaObjective: Female sex workers (FSWs are at an increased risk of human immunodeficiency virus (HIV as well as human papillomavirus (HPV infections and thus have an increased risk of cervical intraepithelial neoplasia (CIN and cervical cancer. We evaluated the feasibility of “screen and treat approach” for cervical cancer prevention and the performance of different screening tests among FSWs.Methods: Women were screened using cytology, VIA (visual inspection with acetic acid, and VILI (visual inspection with Lugol’s iodine and underwent colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated, at the same visit.Results: We screened 300 FSWs of whom 200 (66.67% were HIV uninfected and 100 (33.34% were HIV infected. The overall prevalence of CIN 2–3 lesions was 4.7%. But all women with CIN 2–3 lesions were HIV infected, and thus the prevalence of CIN 2–3 lesions in HIV-infected FSWs was 14/100 (14%, 95% confidence interval: 7.2–20.8. All of them screened positive by all three screening tests. Cold coagulation was well tolerated, with no appreciable side effects.Conclusion: Cervical cancer prevention by “screen and treat” approach using VIA, followed by ablative treatment, in this high-risk group of women is feasible and can be implemented through various targeted intervention programs. Keywords: cytology, VIA, VILI, CIN, cold coagulation, cervical cancer, HPV, FSWs

  14. Zenker’s diverticulum and squamous esophageal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Ion Dina

    2017-10-01

    Full Text Available Zenker’s diverticulum represents a rare esophageal lesion developed especially in the elderly population due to herniation of esophageal mucosa above the cricopharyngeus muscle. The condition leads to food retention, regurgitation, aspiration, and dysphagia in affected patients. Progressive dysphagia also characterizes malignant diseases of the esophagus like squamous esophageal carcinoma that typically appears in male patients in the seventh decade of life, with a history of cigarette smoking and alcohol abuse. We report a case of a male patient who presented with dysphagia for both solids and liquids along with significant weight loss, and who was diagnosed with medium esophageal cancer associated with Zenker’s diverticulum.

  15. Management of Patients With Adenocarcinoma or Squamous Cancer of the Esophagus.

    Science.gov (United States)

    Ilson, David H; van Hillegersberg, Richard

    2018-01-01

    Esophageal cancer is characterized by early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive perioperative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit. Agents that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), or vascular endothelial growth factor, including trastuzumab, ramucirumab, and apatinib, increase response and survival times. Esophageal adenocarcinomas have mutations in tumor protein p53 and mutations that activate receptor-associated tyrosine kinase, vascular endothelial growth factor, and cell cycle pathways, whereas esophageal squamous tumors have a distinct set of mutations. Esophageal cancers develop systems to evade anti-tumor immune responses, but studies are needed to determine how immune checkpoint modification contributes to esophageal tumor development. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2012-12-01

    Full Text Available Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2% of all the lower digestive tract cancers. However, an increased incidence of invasive anal carcinoma is observed in HIV-seropositive population since the widespread of highly active antiretroviral therapy. Human papillomavirus is strongly associated with the pathogenesis of anal cancer. Anal intercourse and a high number of sexual partners appear to be risk factors to develop anal cancer in both sexes. Anal pain, bleeding and a palpable lesion in the anal canal are the most common clinical features. Endo-anal ultrasound is the best diagnosis method to evaluate the tumor size, the tumor extension and the infiltration of the sphincter muscle complex. Chemoradiotherapy plus antiretroviral therapy are the recommended treatments for all stages of localized squamous cell carcinoma of the anal canal in HIV-seropositive patients because of its high rate of cure. Here we present an HIV patient who developed a carcinoma of the anal canal after a long time of HIV infection under highly active antiretroviral therapy with a good virological and immunological response.

  17. Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Rosenlund Andersen, Anja; Bjerring, Ole Steen; Godballe, Christian

    2016-01-01

    SPM. CONCLUSION: In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold......INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally.......004) and hypopharyngeal (OR = 3.9; p cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without...

  18. Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Asgari, Maryam M; Warton, E Margaret; Whittemore, Alice S

    2015-04-01

    The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

  19. High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels

    Directory of Open Access Journals (Sweden)

    Nermina Obralic

    2011-11-01

    Full Text Available High grade prostatic intraepithelial neoplasia (HGPIN is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients. Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL did not differ significantly compared to prostate carcinoma (6.976 ng/mL or benign prostatic hyperplasia (6.07 ng/mL patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133, but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185. Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.

  20. Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer.

    Science.gov (United States)

    Chay, Wen Yee; McCluggage, W Glenn; Lee, Cheng-Han; Köbel, Martin; Irving, Julie; Millar, Joanne; Gilks, C Blake; Tinker, Anna V

    2016-03-01

    The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

  1. Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

    Science.gov (United States)

    Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

    2014-01-01

    Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

  2. Serous tubal intraepithelial carcinoma localizes to the tubal-peritoneal junction: a pivotal clue to the site of origin of extrauterine high-grade serous carcinoma (ovarian cancer).

    Science.gov (United States)

    Seidman, Jeffrey D

    2015-03-01

    which STIC was absent (P not significant). It is concluded that serous tubal intraepithelial carcinoma occurs at and in the immediate vicinity of the TPJ. In combination with the findings that STICs are present in a majority of cases when the TPJ is present, that flat STICs are smaller than papillary STICs, and that lamina propria invasion is more frequent in the presence of STIC, these data support STIC as the precursor of extrauterine high-grade serous carcinoma, they provide important clues to the site of origin of high-grade serous carcinoma (ovarian cancer), and can guide further research.

  3. The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in hiv-positive patients

    Directory of Open Access Journals (Sweden)

    Felicidad Gimenez

    2011-06-01

    Full Text Available CONTEXT: Anal cancer, although a still rare disease, is being observed in ascending rates among some population segments known to be at risk for the development of the disease. Human papillomavirus (HPV infection, immunodepression and anal intercourse are some factors associated with the development of the malignancy. Its similarities to cervical cancer have led to many studies aiming to establish guidelines for detecting and treating precursor lesions of anal cancer, with the goal of prevention. High-resolution anoscopy is routinely used for the diagnosis of anal cancer precursor lesions in many centers but the medical literature is still deficient concerning the role of this diagnostic modality. OBJECTIVES: To evaluate diagnostic validation and precision measures of high-resolution anoscopy in comparison to histopathological results of anal biopsies performed in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas, AM, Brazil. To observe any possible association between some risk factors for the development of anal cancer and the presence of anal squamous intraepithelial lesions. METHODS: A hundred and twenty-eight HIV-positive patients were submitted to anal canal cytological sampling for the detection of HPV infection by a PCR based method. High-resolution anoscopy was then performed after topical application of acetic acid 3% in the anal canal for 2 minutes. Eventual acetowhite lesions that were detected were recorded in respect to location, and classified by their tinctorial pattern, distribution aspect, relief, surface and vascular pattern. Biopsies of acetowhite lesions were performed under local anesthesia and the specimens sent to histopathological analysis. The patients were interviewed for the presence of anal cancer risk factors. RESULTS: The prevalences of anal HPV infection and of anal squamous intraepithelial lesions in the studied population were, respectively, 79% and 39.1%. High-resolution anoscopy

  4. The effect of wool hydrolysates on squamous cell carcinoma cells in vitro. Possible implications for cancer treatment.

    Directory of Open Access Journals (Sweden)

    Tatsiana Damps

    Full Text Available Squamous cell carcinoma of the skin is the second most common cutaneous malignancy. Despite various available treatment methods and advances in noninvasive diagnostic techniques, the incidence of metastatic cutaneous squamous cell carcinoma is rising. Deficiency in effective preventive or treatment methods of transformed keratinocytes leads to necessity of searching for new anticancer agents. The present study aims to evaluate the possibility of using wool hydrolysates as such agents. Commercially available compounds such as 5-fluorouracil, ingenol mebutate, diclofenac sodium salt were also used in this study. The process of wool degradation was based on chemical pre-activation and enzymatic digestion of wool. The effect of mentioned compounds on cell viability of squamous carcinoma cell line and healthy keratinocytes was evaluated. The obtained data show a significantly stronger effect of selected wool hydrolysates compared to commercial compounds (p<0.05 on viability of cells. The wool hydrolysates decreased squamous cell carcinoma cells viability by up to 67% comparing to untreated cells. These results indicate bioactive properties of wool hydrolysates, which affect the viability of squamous carcinoma cells and decrease their number. We hypothesize that these agents may be used topically for treatment of transformed keratinocytes in actinic keratosis and invasive squamous skin cancer in humans.

  5. [Crosssectional survey of human papilloma virus subtype distribution and cervical intraepithelial neoplasia in Shenzhen].

    Science.gov (United States)

    Liang, Ling-yun; Du, Hui; Wang, Chun; Zhang, Wei; Chen, Yun; Qu, Xin-feng; Yang, Bin; Wu, Bo; Wu, Ruo-song; Belinson, Jerome L; Wu, Rui-fang

    2013-02-18

    To investigate the prevalence of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) and pathogenecity of the HPV subtyping and virus loads in Shenzhen district. In the study, 10 000 sexually active women from Shenzhen city and rural areas around were screened for cervical cancer, and all the cases were examined with cytology tests and several kinds of high risk HPV (HR-HPV) tests. Those with cytology ≥atypical squamous cells of undetermined sign (ASC-US) or positive HPV results underwent colposcopy with biopsy for a pathological diagnosis. The average age of this study population was 38.9 years. The total prevalence of HPV infection was 16.6%, with age-specific prevalence increasing with age. The morbidity rate of the low grade cervical intraepithelial neoplasia CIN1 was 17.0%, but that with those aged ≥55 years showed a sharp drop. The morbidity rate of the high grade cervical intraepithelial neoplasia CIN2/3 was 2.6%, and was higher in the 45 to 59 years age group than in the 25 to 44 years age group. HR-HPV infection was an obvious relevant factor of CIN1 and CIN2/3, and the OR values increased as the virus loads increased, but they had different relevant HPV subtypes. We found that HPV-16, -58, -31, -33, -18 were the first five ones for CIN2/3 while HPV-39, -58, -59, -52, -66 for CIN1. There is a high level of HPV infection and CIN in Shenzhen district. The prevalence of HPV infection has a trend to increase with age, and the people aged 45 years and more are key objects for CIN2/3 screening, with the virus load and subtyping of HR-HPV infection as indicative factors.

  6. GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers.

    Science.gov (United States)

    Park, Yu Rang; Bae, Soo Hyeon; Ji, Wonjun; Seo, Eul Ju; Lee, Jae Cheol; Kim, Hyeong Ryul; Jang, Se Jin; Choi, Chang Min

    2017-11-01

    Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. © 2017 The Korean Academy of Medical Sciences.

  7. Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma

    NARCIS (Netherlands)

    Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Vander Poorten, Vincent; Haigentz, Missak; Langendijk, Johannes A.; de Bree, Remco; Hinni, Michael L.; Mendenhall, William M.; Paleri, Vinidh; Rinaldo, Alessandra; Werner, Jochen A.; Takes, Robert P.; Ferlito, Alfio

    Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the

  8. Investigating a case of possible field cancerization in oral squamous cell carcinoma by the use of next-generation sequencing

    DEFF Research Database (Denmark)

    Tabatabaeifar, Siavosh; Larsen, Martin J.; Larsen, Stine R.

    2017-01-01

    Objectives Local recurrence and the development of second primary tumors (SPT) are important factors that can influence the survival rate of oral squamous cell carcinoma (OSCC) patients. We investigate the concept of field cancerization which proposes that normal tissue adjacent to the primary...

  9. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    International Nuclear Information System (INIS)

    Oue, Erika; Lee, Ji-Won; Sakamoto, Kei; Iimura, Tadahiro; Aoki, Kazuhiro; Kayamori, Kou; Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo; Yamaguchi, Akira

    2012-01-01

    Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

  10. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

  11. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer.

    Science.gov (United States)

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy.

  12. Cervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16 prevalence and vaccination impact.

    Science.gov (United States)

    Pérez-Castro, Sonia; Lorenzo-Mahía, Yolanda; Iñarrea Fernández, Amparo; Lamas-González, María José; Sarán-Díez, María Teresa; Rubio-Alarcón, Joaquín; Reboredo-Reboredo, María Consuelo; Mosteiro-Lobato, Sonia; López-Miragaya, Isabel; Torres-Piñón, Julio; Melón-García, Santiago

    2014-10-01

    The etiology of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) can influence the efficacy of Public Health preventive strategies. This study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of bivalent vaccination, and the distribution of HPV 16 in squamous lesions. Ninety-four histologically confirmed cases of CIN2+ (2009-2010) were retrospectively studied: 23 CIN2, 58 CIN3- squamous carcinoma in situ (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany) was performed on the cervical specimens. Bivalent vaccination impact was calculated, based on regional vaccination coverage data, local HR-HPV prevalence, and reported efficacy (direct and cross-protection) of the vaccine. HR-HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8-58.2%) and HPV 31 (9.3%-12.1%), considering single infections or single-multiple infections, respectively (hierarchical attribution). In squamous lesions, HPV 16 prevalence in women younger than 45 years of age increased in severe lesions (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or by 62.7% (direct and cross-protection). HPV vaccination could have a great impact in women younger than 45 years of age due to the high prevalence of HPV 16 in their lesions. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Squamous cell carcinoma of the anus-an opportunistic cancer in HIV-positive male homosexuals

    Science.gov (United States)

    Gervaz, Pascal; Calmy, Alexandra; Durmishi, Ymer; Allal, Abdelkarim S; Morel, Philippe

    2011-01-01

    Squamous cell carcinoma of the anus (SCCA) is a common cancer in the human immunodeficiency virus (HIV)-infected population, and its incidence continues to increase in male homosexuals. Combined chemoradiation with mitomycin C and 5-fluorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy (HAART), however, recent data indicate that: (1) most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and (2) this approach is associated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recurrence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in middle-aged HIV-positive male homosexuals. In this population, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses (HPVs). Large-scale cancer-prevention strategies (routine anuscopy and anal papanicolaou testing) should be implemented in this population. In addition, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination. PMID:21799644

  14. Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous Cell Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Harry W. Haverkos

    2017-11-01

    Full Text Available Cervical cancer (CC is the fourth most common cancers among women worldwide. Human papillomaviruses (HPVs play a major role in the etiology of CC, with several lines of epidemiologic and experimental evidence supporting a role for non-viral (co-carcinogens and host genetic factors in controlling the risk for progression to neoplasia among HPV-infected individuals. The role of co-carcinogens in the development of CC is significant in the developing world where poor sanitation and other socio-economic conditions increase the infectious cancer burden. Here, we discuss how exposure to environmental factors such as coal tar derivatives from cigarette smoking, tar-based sanitary products, and inhaled smoke from biomass-burning stoves, could activate host pathways involved in development of HPV-associated squamous cell cancers in resource-limited settings. Understanding interactions between these pathways with certain oncogenic HPV genotypes may guide implementation of strategies for control and treatment of HPV-associated cancers that develop in populations at high risk of exposure to various co-carcinogens.

  15. Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia.

    Science.gov (United States)

    Elwood, J Mark; Youlden, Danny R; Chelimo, Carol; Ioannides, Sally J; Baade, Peter D

    2014-02-01

    Increases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia. Incidence data for 1982-2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression. The incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50-69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC. Incidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.

    Science.gov (United States)

    Hernandes, Camila; Pereira, Ana Maria Soares; Severino, Patricia

    2017-02-01

    Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.

  17. Maximizing Benefits from Maintenance Pemetrexed with Stereotactic Ablative Radiotherapy in Oligoprogressive Non-Squamous Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shao-Lun Lu

    2016-08-01

    Full Text Available Maintenance pemetrexed offers survival benefit with well-tolerated toxicities for advanced non-squamous non-small cell lung cancer (NSCLC. We present 3 consecutively enrolled patients with advanced non-squamous NSCLC, receiving stereotactic ablative radiotherapy (SABR for oligoprogressive disease during maintenance pemetrexed. All of them had sustained local control of thoracic oligoprogression after the SABR, while maintenance pemetrexed were kept for additionally long progression-free interval. SABR targeting oligoprogression with continued pemetrexed is an effective and safe approach to extend exposure of maintenance pemetrexed, thus maximizing the benefit from it.

  18. HPV prevalence in a Mid-European oral squamous cell cancer population: a cohort study.

    Science.gov (United States)

    Dalla Torre, Daniel; Burtscher, Doris; Soelder, Elisabeth; Offermanns, Vincent; Rasse, Michael; Puelacher, Wolfgang

    2018-04-29

    HPV infection has been investigated intensively regarding oropharyngeal carcinoma. However, there is still lack of knowledge about the impact of oral HPV infections concerning oral squamous cell carcinoma. The present study investigates the prevalence of oral HPV infection in such patients, identifying possible differences between HPV+ and HPV- patients. 106 consequent patients were investigated. After completion of a study questionnaire regarding risk factors, a brush smear sample was taken in each subject to identify the individual oral HPV status (overall/low risk/high risk). 35.8% of the patients were tested positive for HPV in the oral cavity (14% low risk, 28.3% high risk). Patients with oral HPV infection and high risk HPV infection were significantly younger (pHPV infection. Finally, patients with high risk oral HPV infection had experienced more tooth extractions during their lifetime. Oral HPV infections may influence the course of disease of oral squamous cell carcinoma as HPV+ patients are about 10 years younger. It seems that high alcohol consumption facilitates high risk HPV infection. It may be presumed that both alcohol consumption and high risk oral HPV infection act synergistically, explaining earlier cancer onset. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  20. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

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    Minami S

    2015-01-01

    Full Text Available Seigo Minami,1 Takashi Kijima2 1Department of Respiratory Medicine, Osaka Police Hospital, 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan Abstract: Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC. Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be

  1. Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

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    Cosimo De Nunzio

    2013-06-01

    Full Text Available Purpose: To evaluate the risk of prostate cancer (PCa on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN. Materials and methods: From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE were scheduled for trans-rectal ultrasound (TRUS guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. Results: A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22% men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34% still showed HGPIN, 15 (35% were diagnosed with PCa and 9 (21% presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04. Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Conclusions: Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.

  2. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Lehtinen, Matti; Ault, Kevin A; Lyytikainen, Erika

    2011-01-01

    High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined....

  3. Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

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    Firnhaber, Cynthia; Swarts, Avril; Goeieman, Bridgette; Rakhombe, Ntombi; Mulongo, Masangu; Williamson, Anna-Lise; Michelow, Pam; Ramotshela, Sibongile; Faesen, Mark; Levin, Simon; Wilkin, Timothy

    2017-12-15

    HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

  4. Clinical and genetic features of lung squamous cell cancer in never-smokers

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    Zhang, Yang; Li, Hang; Cheng, Chao; Zheng, Difan; Zheng, Shanbo; Li, Yuan; Shen, Xuxia; Hu, Haichuan; Cai, Deng; Wang, Shengfei; Zhang, Yawei; Xiang, Jiaqing; Sun, Yihua; Zhang, Jie; Chen, Haiquan

    2016-01-01

    To evaluate the importance of specific driver mutations to the development and outcome of lung squamous cell cancer (SQCC) in never-smokers, we assessed the clinicopathological characteristics and outcomes of 597 patients who underwent complete resection of SQCCs. In total, 88 (14.7%) never-smokers and 509 (85.3%) ever-smokers were compared. The never-smokers included more females (42.05% vs. 1.57%, P never-smokers were more often poorly differentiated (70.45% vs. 53.24%, P = 0.010) and more often contained oncogenic mutations (21.05% vs 11.05%, P = 0.023), particularly EGFR mutations (13.16% vs 3.40%, P = 0.001). Never-smokers also tended to have poorer OS than smokers. Our results suggest lung SQCCs in never-smokers are a subtype distinct from SQCCs occurring in smokers. PMID:27092882

  5. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna

    2008-01-01

    BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We...... interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. RESULTS: Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p......p13.3 independently predicted poor survival in multivariate analysis. CONCLUSION: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict...

  6. Clinical and genetic features of lung squamous cell cancer in never-smokers.

    Science.gov (United States)

    Huang, Yangle; Wang, Rui; Pan, Yunjian; Zhang, Yang; Li, Hang; Cheng, Chao; Zheng, Difan; Zheng, Shanbo; Li, Yuan; Shen, Xuxia; Hu, Haichuan; Cai, Deng; Wang, Shengfei; Zhang, Yawei; Xiang, Jiaqing; Sun, Yihua; Zhang, Jie; Chen, Haiquan

    2016-06-14

    To evaluate the importance of specific driver mutations to the development and outcome of lung squamous cell cancer (SQCC) in never-smokers, we assessed the clinicopathological characteristics and outcomes of 597 patients who underwent complete resection of SQCCs. In total, 88 (14.7%) never-smokers and 509 (85.3%) ever-smokers were compared. The never-smokers included more females (42.05% vs. 1.57%, P smokers were more often poorly differentiated (70.45% vs. 53.24%, P = 0.010) and more often contained oncogenic mutations (21.05% vs 11.05%, P = 0.023), particularly EGFR mutations (13.16% vs 3.40%, P = 0.001). Never-smokers also tended to have poorer OS than smokers. Our results suggest lung SQCCs in never-smokers are a subtype distinct from SQCCs occurring in smokers.

  7. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

    Science.gov (United States)

    Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

    2015-01-01

    A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  8. Does endoscopic ultrasound improve detection of locally recurrent anal squamous-cell cancer?

    Science.gov (United States)

    Peterson, Carrie Y; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Garcia-Aguilar, Julio; Patil, Sujata; Temple, Larissa K

    2015-02-01

    Evaluating patients for recurrent anal cancer after primary treatment can be difficult owing to distorted anatomy and scarring. Many institutions incorporate endoscopic ultrasound to improve detection, but the effectiveness is unknown. The aim of this study is to compare the effectiveness of digital rectal examination and endoscopic ultrasound in detecting locally recurrent disease during routine follow-up of patients with anal cancer. This study is a retrospective, single-institution review. This study was conducted at an oncologic tertiary referral center. Included were 175 patients with nonmetastatic anal squamous-cell cancer, without persistent disease after primary chemoradiotherapy, who had at least 1 posttreatment ultrasound and examination by a colorectal surgeon. The primary outcomes measured were the first modality to detect local recurrence, concordance, crude cancer detection rate, sensitivity, specificity, and predictive value. Eight hundred fifty-five endoscopic ultrasounds and 873 digital rectal examinations were performed during 35 months median follow-up. Overall, ultrasound detected 7 (0.8%) mesorectal and 32 (3.7%) anal canal abnormalities; digital examination detected 69 (7.9%) anal canal abnormalities. Locally recurrent disease was found on biopsy in 8 patients, all detected first or only with digital examination. Four patients did not have an ultrasound at the time of diagnosis of recurrence. The concordance of ultrasound and digital examination in detecting recurrent disease was fair at 0.37 (SE, 0.08; 95% CI, 0.21-0.54), and there was no difference in crude cancer detection rate, sensitivity, specificity, and negative or positive predictive values. The heterogeneity of follow-up timing and examinations is not standardized in this study but is reflective of general practice. Endoscopic ultrasound did not provide any advantage over digital rectal examination in identifying locally recurrent anal cancer, and should not be recommended for

  9. Fractal analysis of cervical intraepithelial neoplasia.

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    Markus Fabrizii

    Full Text Available INTRODUCTION: Cervical intraepithelial neoplasias (CIN represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. METHODS: Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. RESULTS: Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. CONCLUSION: Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.

  10. Fibroblast growth factor receptor (FGFR) alterations in squamous differentiated bladder cancer: a putative therapeutic target for a small subgroup.

    Science.gov (United States)

    Baldia, Philipp H; Maurer, Angela; Heide, Timon; Rose, Michael; Stoehr, Robert; Hartmann, Arndt; Williams, Sarah V; Knowles, Margaret A; Knuechel, Ruth; Gaisa, Nadine T

    2016-11-01

    Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high. In the TCGA "squamous-like" subtype FGFR3 mutations were found in 4.9% and correlated with high FGFR3 RNA expression. Mutations of FGFR1 and FGFR2 were less frequent (2.4% and 1.2%). Hence, our comprehensive study provides novel insights into a subgroup of squamous differentiated bladder tumors that hold clues for novel therapeutic regimens and may benefit from FGFR3-targeted therapies.

  11. Potential targets for lung squamous cell carcinoma

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    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  12. Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

    Science.gov (United States)

    Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

    2018-04-01

    In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area

  13. Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer?

    Science.gov (United States)

    COGHILL, Anna E.; SHIELS, Meredith S.; RYCROFT, Randi K.; COPELAND, Glenn; FINCH, Jack L.; HAKENEWERTH, Anne M.; PAWLISH, Karen S.; ENGELS, Eric A.

    2015-01-01

    Objective Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. Design Population-based registry Methods We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991–2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons to the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. Results HIV-infected persons had an excess risk of rectal SCC compared to the general population (SIR=28.9; 95%CI 23.2–35.6), similar to the increase for anal SCC (SIR=37.3). Excess rectal SCC risk was most pronounced among HIV-infected men who have sex with men (MSM, SIR=61.2). Risk was not elevated for rectal non-SCC (SIR=0.88) or colon non-SCC (SIR=0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio=1.86; 95%CI 1.04–3.31). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. Conclusions HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumor location is needed to prove that rectal SCC is a distinct entity. PMID:26372482

  14. Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

    Science.gov (United States)

    Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

    2017-11-01

    The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

  15. Patient Characteristics, Treatment Patterns and Prognostic Factors in Squamous Cell Bladder Cancer.

    Science.gov (United States)

    Zahoor, Haris; Elson, Paul; Stephenson, Andrew; Haber, Georges-Pascal; Kaouk, Jihad; Fergany, Amr; Lee, Byron; Koshkin, Vadim; Ornstein, Moshe; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian; Grivas, Petros

    2018-04-01

    Squamous cell carcinoma (SCC) is an uncommon histologic subtype of bladder cancer with limited data on treatment patterns, outcomes, and prognostic factors. "Real world" information might inform decision-making, prognostic estimates, and clinical trial designs. A retrospective review of patients with tissue-confirmed bladder SCC treated at Cleveland Clinic from 2007 to 2016 was performed. Data on patient characteristics, treatment patterns, and clinical follow-up were extracted. Univariate analysis was used to identify predictors of overall survival (OS), recurrence-free survival (RFS) and time to recurrence. Of 58 identified patients, 42 had complete data available. Median age at diagnosis was 67 years (range, 37-90). Hematuria was the most common (71%) presenting symptom; 32 patients had pure SCC and 10 predominant/extensive squamous differentiation without major differences noted in clinicopathologic variables or outcomes among those 2 groups. Overall, 35 patients underwent cystectomy with 5 receiving neoadjuvant and 1 adjuvant chemotherapy, whereas 3 had chemotherapy for recurrent disease. Of patients with cystectomy, most had locally advanced disease (75% pT3/4, 35% pN+). Overall, 10 patients progressed and 14 died; median OS was not reached. The 2-year estimated OS, RFS, and cumulative incidence of recurrence were 61% ± 9%, 50% ± 9%, and 32% ± 9%, respectively. Hydronephrosis, older age (70 years or older), lymphovascular invasion, nodal metastases, and advanced T stage were associated with 1 or more poor outcomes. In patients with resectable bladder SCC, radical cystectomy remains the main treatment modality. The role of perioperative chemotherapy remains unclear. The identified prognostic factors might be helpful for prognostication, treatment discussion, and trial eligibility/stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer.

    Science.gov (United States)

    Tenjimbayashi, Yuri; Onuki, Mamiko; Hirose, Yusuke; Mori, Seiichiro; Ishii, Yoshiyuki; Takeuchi, Takamasa; Tasaka, Nobutaka; Satoh, Toyomi; Morisada, Tohru; Iwata, Takashi; Miyamoto, Shingo; Matsumoto, Koji; Sekizawa, Akihiko; Kukimoto, Iwao

    2017-01-01

    Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences. The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins. Among 52 isolates of HPV52 (CIN1, n  = 20; CIN2/3, n  = 21; ICC, n  = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n  = 21; CIN2/3, n  = 19; ICC, n  = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed

  17. Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Enjiao Zhang

    Full Text Available MicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.The genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs and 95% confidence intervals (95%CIs were calculated to assess the association. All analyses were performed using the SPSS software. 3.154( 0.001.For miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555-6.397, P value was 0.001. The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.These findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

  18. Squamous cell carcinoma of the trachea in a non-smoking woman after radiation therapy for breast cancer

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    Ishiwa, Naoki; Yamada, Kouzou; Nakayama, Haruhiko; Noda, Kazumasa [Kanagawa Cancer Center, Yokohama (Japan); Kameda, Youichi; Maehara, Takamitsu

    2000-04-01

    Few cases of squamous cell carcinoma of the trachea have been reported in non-smoking women. We report one case which was probably due to radiation therapy. A 50-year-old non-smoking woman was referred to our hospital because wheezing and dyspnea had been aggravated for 3 months. She had received radiation therapy ({sup 60}Cobalt) after standard radical mastectomy for right breast cancer 13 years previously. Bronchoscopic findings and chest CT scan showed tracheal stenosis due to the tumor. Sleeve resection of the trachea was performed, and the tumor was histologically diagnosed as poorly differentiated squamous cell carcinoma. We may consider this case to be radiation-induced cancer compatible with the most strict criteria of radiation induced malignancy. (author)

  19. Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

    Science.gov (United States)

    Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

    2018-03-01

    Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco

  20. Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2018-04-10

    Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

  1. Overexpression of DNA damage-induced 45 α gene contributes to esophageal squamous cell cancer by promoter hypomethylation

    Directory of Open Access Journals (Sweden)

    Wang Bao xiang

    2012-02-01

    Full Text Available Abstract Background Environmental factors-induced dysfunction of esophageal squamous epithelium, including genomic DNA impairment and apoptosis, play an important role in the pathogenesis of esophageal squamous cell cancer. DNA damage-induced 45α (GADD45α has been found promoting DNA repair and removing methylation marker, Therefore, in this study we will investigate whether GADD45α expression is induced and its mechanism in esophageal squamous cell cancer. Methods Two human esophageal squamous cell lines (ESCC, ECA109 and KYSE510 were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS. Lipofectamine 2000 was used to transfect cells. mRNA level of GADD45α was measured by reverse transcription-quantitive PCR (RT-qPCR, protein level of GADD45α was detected by western blot and Immunohistochemistry. Global DNA methylation of tissue sample was measured using the Methylamp Global DNA Methylation Quantification Ultra kit (Epigentek Group and promoter methylation was measured by bisulfite sequencing. Results GADD45a mRNA and protein levels were increased significantly in tumor tissue than that in adjacent normal tissue. Hypomethylation of global genomic DNA and GADD45α promoter were found in ESCC. The cell sensitivity to Cisplatin DDP was decreased significantly in Eca109 and Kyse510 cells, in which GADD45α expression was down-regulated by RNA interference (RNAi. In addition, silence of GADD45a expression in ESCC cells inhibited proliferation and promoted apoptosis. Conclusion Overexpression of GADD45α gene is due to DNA hypomethylation in ESCC. GADD45α may be a protective factor in DDP chemotherapy for esophageal squamous cell carcinoma.

  2. A review of squamous cell vulvar cancers in Waikato region, New Zealand.

    Science.gov (United States)

    Dass, Prashanth Hari; Kuper-Hommel, Marion Jj

    2017-11-10

    Squamous cell vulvar cancers (SCVC) are rare. Although management guidelines have recently been published, New Zealand studies presenting "real world" outcomes are limited. Retrospective single-centre review of SCVC diagnosed between 1 January 2000 and 31 August 2015. Clinical characteristics and outcomes were reviewed. Among 47 cases reviewed, 38 were ethnically European and 9 Māori. Cases identified as Stage 1 (16), Stage 2 (5), Stage 3 (17), Stage 4 (9). For Stages 1, 2, 3 and 4, (16, 4, 17 and 6) were managed by local excision; (9, 1, 14 and 2) by node dissection and (2, 1, 3 and 5) by chemoradiotherapy respectively. Wound cellulitis (10) and lymphedema (8) were the commonest acute and late complication, respectively. Seven patients were treated with 5-Fluorouracil and Mitomycin, and four received weekly Cisplatin. Grade 3 toxicities seen in five cases treated with 5-Fluorouracil and Mitomycin versus none in the Cisplatin group. No local recurrences observed in patients treated with chemoradiation. Patients with Age Adjusted Charlson Comorbid Index Score (ACCIS) <5 had better overall survival (OS) compared to scores ≥5 (60% versus 41%) with 33 months median follow-up. Five-year OS and disease-free specific survival was 73% and 94% (Stage 1), 40% and 60% (Stage 2), 44% and 59% (Stage 3) and 29% (Stage 4) respectively. We present "real world" outcomes of vulvar cancers in this older and comorbid population. Larger, prospective multi-centre studies are proposed.

  3. Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

    Science.gov (United States)

    Bublik, Michael; Head, Christian; Benharash, Peyman; Paiva, Marcos; Eshraghi, Adrian; Kim, Taiho; Saxton, Romaine

    2006-06-01

    This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

  4. Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

    Science.gov (United States)

    Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

    2018-05-01

    The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

  5. [Conjunctival squamous cell carcinoma: paradoxical response to interferon eyedrops].

    Science.gov (United States)

    Mata, E; Conesa, E; Castro, M; Martínez, L; de Pablo, C; González, M L

    2014-07-01

    A 67 year-old male seen for a longstanding corneal-conjunctival tumor. topical interferon α2b (IFN-α2b) 10 U/ml. A significant increase in lesion size was observed after 8 weeks. A surgical excision with cryotherapy was then performed. Pathological examination confirmed the diagnosis of squamous cell carcinoma. At this time the patient was found to have a positive HIV serology. Conjunctival intraepithelial neoplasia (CIN) is a pre-cancerous lesion of the ocular surface. Medical treatment of CIN is essentially with IFN-α2b due to its antiviral/antitumor properties. In patients with HIV, treatment response could be paradoxical. We recommend serology for HIV before treatment with topical IFN-α2b. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

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    Helen H Yu

    2016-08-01

    Full Text Available Aim To identify and characterize cancer stem cells (CSC in moderately differentiated buccal mucosa squamous cell carcinoma (MDBMSCC. Methods 4μm-thick formalin-fixed paraffin-embedded MDBMSCC samples from six patients underwent 3,3-diaminobenzidine (DAB immunohistochemical (IHC staining for the embryonic stem cell (ESC markers NANOG, OCT4, SALL4, SOX2 and pSTAT3; cancer stem cell marker CD44; squamous cell carcinoma (SCC marker EMA; and endothelial marker CD34. The transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, STAT3 and CD44 were studied using NanoString gene expression analysis and colorimetric in situ hybridization (CISH for NANOG, OCT4, SOX2, SALL4 and STAT3. Results DAB and immunofluorescent (IF IHC staining demonstrated the presence of (1 an EMA+/CD44+/SOX2+/SALL4+/OCT4+/pSTAT3+/NANOG+ CSC subpopulation within the tumor nests; (2 an EMA-/CD44-/CD34-/SOX2+/OCT4+/pSTAT3+/NANOG+ subpopulation within the stroma between the tumor nests; and (3 an EMA-/CD44-/CD34+/SOX2+/ SALL4+/OCT4+/pSTAT3+/NANOG+ subpopulation on the endothelium of the microvessels within the stroma. The expression of CD44, SOX2, SALL4, OCT4, pSTAT3 and NANOG was confirmed by the presence of mRNA transcripts, using NanoString analysis and NANOG, OCT4, SOX2, SALL4 and STAT3 by CISH staining. Conclusion This study demonstrated a novel finding of three separate CSC subpopulations within MDBMSCC: (1 within the tumor nests expressing EMA, CD44, SOX2, SALL4, OCT4, pSTAT3 and NANOG; (2 within the stroma expressing SOX2, SALL4, OCT4, pSTAT3 and NANOG; and (3 on the endothelium of the microvessels within the stroma expressing CD34, SOX2, SALL4, OCT4, pSTAT3 and NANOG.

  7. EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    OpenAIRE

    Kodali Venkataramana; Prasad Usha

    2017-01-01

    BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelia...

  8. Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Han, Jing; Fujisawa, Toshio; Husain, Syed R; Puri, Raj K

    2014-01-01

    Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy

  9. Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

    International Nuclear Information System (INIS)

    Rodríguez-Berriguete, Gonzalo; Paniagua, Ricardo; Royuela, Mar; Fraile, Benito; Bethencourt, Fermín R de; Prieto-Folgado, Angela; Bartolome, Nahikari; Nuñez, Claudia; Prati, Bruna; Martínez-Onsurbe, Pilar; Olmedilla, Gabriel

    2010-01-01

    In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation. Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2)

  10. Genetics Home Reference: head and neck squamous cell carcinoma

    Science.gov (United States)

    ... and neck squamous cell carcinoma Head and neck squamous cell carcinoma Printable PDF Open All Close All Enable Javascript ... Consumer Version: Overview of Mouth, Nose, and Throat Cancers Orphanet: Squamous cell carcinoma of head and neck University of Michigan ...

  11. EGFR inhibitor C225 increases the radiosensitivity of human lung squamous cancer cells

    Directory of Open Access Journals (Sweden)

    Yang Ruijie

    2010-10-01

    Full Text Available Abstract Background The purpose of the present study is to investigate the direct biological effects of the epidermal growth factor receptor (EGFR inhibitor C225 on the radiosensitivity of human lung squamous cancer cell-H520. H520 cells were treated with different dosage of 60Co γ ray irradiation (1.953 Gy/min in the presence or absence of C225. The cellular proliferation, colony forming capacity, apoptosis, the cell cycle distribution as well as caspase-3 were analyzed in vitro. Results We found that C225 treatment significantly increased radiosensitivity of H-520 cells to irradiation, and led to cell cycle arrest in G1 phase, whereas 60Co γ ray irradiation mainly caused G2 phase arrest. H-520 cells thus displayed both the G1 and G2 phase arrest upon treatment with C225 in combination with 60Co γ ray irradiation. Moreover, C225 treatment significantly increased the apoptosis percentage of H-520 cells (13.91% ± 1.88% compared with the control group (5.75% ± 0.64%, P Conclusion In this regard, C225 treatment may make H-520 cells more sensitive to irradiation through the enhancement of caspase-3 mediated tumor cell apoptosis and cell cycle arrest.

  12. Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

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    Adrian Biddle

    2016-02-01

    Full Text Available Cancer stem cells (CSCs drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT and mesenchymal-to-epithelial transition (MET to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC, we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

  13. Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

    2016-02-01

    Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

  14. Sun protection for preventing basal cell and squamous cell skin cancers.

    Science.gov (United States)

    Sánchez, Guillermo; Nova, John; Rodriguez-Hernandez, Andrea Esperanza; Medina, Roger David; Solorzano-Restrepo, Carolina; Gonzalez, Jenny; Olmos, Miguel; Godfrey, Kathie; Arevalo-Rodriguez, Ingrid

    2016-07-25

    'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks. To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population. We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials. We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events. Two review authors independently selected studies for eligibility using

  15. Patients with newly diagnosed cervical cancer should be screened for anal human papilloma virus and anal dysplasia: Results of a pilot study using a STELLA computer simulation and economic model

    OpenAIRE

    Eli D. Ehrenpreis; Dylan G. Smith

    2018-01-01

    Background: Women with cervical cancer often have anal human papillomavirus (HPV) infection and anal dysplasia. However, effectiveness of anal HPV screening is unknown. Methods: A dynamic model was constructed using STELLA. Populations are represented as ''stocks'' that change according to model rates. Initial anal cytology in new cervical cancer patients, dysplasia progression and regression, cost of treating high-grade squamous intraepithelial lesions (HSIL), and lifetime costs for anal can...

  16. [Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

    Science.gov (United States)

    Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

    2012-01-01

    Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

  17. Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis.

    Science.gov (United States)

    Chen, Xiaohang; Yan, Bingqing; Lou, Huihuang; Shen, Zhenji; Tong, Fangjia; Zhai, Aixia; Wei, Lanlan; Zhang, Fengmin

    2018-04-01

    Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Shibata

    2011-09-01

    Full Text Available Esophageal squamous cancer (ESC is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22% in advanced ESC tumors and ESC cell lines (3/10. The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT.

  19. PIAS3 expression in squamous cell lung cancer is low and predicts overall survival

    International Nuclear Information System (INIS)

    Abbas, Rime; McColl, Karen S; Kresak, Adam; Yang, Michael; Chen, Yanwen; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-01-01

    Unlike lung adenocarcinoma, little progress has been made in the treatment of squamous cell lung carcinoma (SCC). The Cancer Genome Atlas (TCGA) has recently reported that receptor tyrosine kinase signaling pathways are altered in 26% of SCC tumors, validating the importance of downstream Signal Transducers and Activators of Transcription 3 (STAT3) activity as a prime therapeutic target in this cancer. In the present report we examine the status of an endogenous inhibitor of STAT3, called Protein Inhibitor of Activated STAT3 (PIAS3), in SCC and its potential role in this disease. We examine PIAS3 expression in SCC tumors and cell lines by immunohistochemistry of a tissue microarray and western blotting. PIAS3 mRNA expression and survival data are analyzed in the TCGA data set. SCC cell lines are treated with curcumin to regulate PIAS3 expression and cell growth. PIAS3 protein expression is decreased in a majority of lung SCC tumors and cell lines. Analysis of PIAS3 mRNA transcript levels demonstrated that low PIAS3 levels predicted poor survival; Cox regression analysis revealed a hazard ratio of 0.57 (95% CI: 0.37–0.87), indicating a decrease in the risk of death by 43% for every unit elevation in PIAS3 gene expression. Curcumin treatment increased endogenous PIAS3 expression and decreased cell growth and viability in Calu-1 cells, a model of SCC. Our results implicate PIAS3 loss in the pathology of lung SCC and raise the therapeutic possibility of upregulating PIAS3 expression as a single target that can suppress signaling from the multiple receptor tyrosine kinase receptors found to be amplified in SCC

  20. Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Yang, Huilun; Hu, Haiyang; Gou, Yanling; Hu, Yuhong; Li, Hui; Zhao, Hongwei; Wang, Beidi; Li, Peiling; Zhang, Zongfeng

    2018-04-01

    Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis. Expression of the epithelial-mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group. The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p  0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p  0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05). Combined detection of Twist1 and Snail1 in SCCA-positive biopsy

  1. Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation

    International Nuclear Information System (INIS)

    Silva, Sonali S. de; Payne, Geoffrey S.; Morgan, Veronica A.; Ind, Thomas E.J.; Shepherd, John H.; Barton, Desmond P.J.; Souza, Nandita M. de

    2009-01-01

    To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR=1,500 ms, TE=135 ms). tCho, 2 ppm and -CH 2 lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. 1 H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p=0.03) and 2 ppm (p=0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH 2 lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH 2 lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer. (orig.)

  2. [Treatment results for different categories of vaginal intraepithelial neoplasia with electrocoagulation, 5-fluorouracil and combined treatment].

    Science.gov (United States)

    Veloz-Martínez, María Guadalupe; Quintana-Romero, Verónica; Contreras-Morales, María del Rosario Sandra; Jiménez-Vieyra, Carlos Ramón

    2015-10-01

    Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer. To compare the results of the treatment for the different categories of VAIN with electrocoagulation, 5-fluorouracil and combined treatment. Observational an analytical study. We stablished groups according to the category of VAIN evaluating and comparing remission, persistence, recurrence, or progression of the disease ac- cording to the received treatment, with a 1-year follow up. The results were compared by chi2 and Kruskal Wallis. The statistics analysis was done with the SPSS program version 20. One hundred thirty seven patients between 20 and 81 years of age (mean age: 52.49 years) were included. Seventy-four percent of the patients had a history of premalignant or malignant cervical lesions. Seventy-four patients had VAIN I, 34 patients had VAIN II, 22 patients had VAIN III and there were seven cases of vaginal carcinoma in situ. Fifty-eight patients were treated with electrocoagulation, 55 patients were treated with 5-FU, 16 patients had combined treatment, and eight patients received expectant management. Sixty three percent of patients had total remission of the lesion, 34% had persistence and 3% showed progression, and there were no cases of recurrence. Results were better in patients with VAIN I treated with 5-FU (bigger percentage of remission P .026), for the remaining categories of VAIN, no treatment showed superior results. The superior response occurs in patients with VAIN I treated with 5-FU. None of the treatments achieves a 100% remission. The VAIN frequency is high, patients with a history of malignant or premalignant cervical pathology should undergo a closer surveillance through cytocolposcopic control with respect to the remaining population.

  3. Resultados histológicos e detecção do HPV em mulheres com células escamosas atípicas de significado indeterminado e lesão escamosa intra-epitelial de baixo grau na colpocitologia oncológica Histological results and HPV detection in women with pap smear showing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    André Luis Ferreira Santos

    2004-07-01

    cells of unknown significance (ASCUS or low-grade squamous intraepithelial lesions (LSIL. METHODS: a cross-sectional study comprising 161 women referred to the Taubaté University Hospital due to ASCUS/LSIL, between August 2000 and September 2002. All women responded to a questionnaire regarding sociodemographic and reproductive characteristics and were subjected to gynecological examination with specimen collection for Pap test and HCII, along with colposcopy and eventual cervical biopsy. The relationship between HCII results and age, use of condom, oral hormonal contraception, and smoking were evaluated by the chi-square test. The sensitivity, specificity, positive and negative predictive values of both Pap test and HCII were calculated. All calculations were performed within 95% confidence intervals. RESULTS: sixty-seven percent of the women that tested positive for HPV were less than 30 years old. Pap smear and HCII showed the same 82% sensitivity in detecting CIN2/3 when the threshold for a positive Pap result was ASCUS, LSIL or HSIL. Pap smear specificity and positive predictive values were substantially increased when only HSIL results were considered as positive (from 29 to 95% and 12 to 50%, respectively. These figures were superior to those of HCII, but at the expense of an expressive loss of sensitivity (from 82% to 41%. CONCLUSIONS: our results substantiate the potential of HCII in detecting CIN2/3 among women referred due to ASCUS/LSIL.

  4. S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

    Science.gov (United States)

    Rector, Jeff; Kapil, Sasha; Treude, Kelly J; Kumm, Phyllis; Glanzer, Jason G; Byrne, Brendan M; Liu, Shengqin; Smith, Lynette M; DiMaio, Dominick J; Giannini, Peter; Smith, Russell B; Oakley, Greg G

    2017-02-07

    Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

  5. Avaliação da conduta conservadora na lesão intraepitelial cervical de alto grau Evaluación de la conducta conservadora en la lesión intraepitelial cervical de alto grado Evaluation of conservative management of high-grade cervical squamous intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    Nelson Shozo Uchimura

    2012-06-01

    transversal y retrospectivo realizado con 509 mujeres (15-76 años atendidas en el período de 1996 a 2006, con colpocitología oncótica alterada, en un servicio público de referencia en Maringá, Sur de Brasil. Los datos fueron colectados de los prontuarios médicos y se estudiaron las variables diagnóstico definitivo, tipos de tratamiento, ocurrencia de la lesión y reincidencias y se analizaron por medio de pruebas de asociación de chi-cuadrado de Pearson y exacto de Fisher. RESULTADOS: La lesión intraepitelial cervical de alto grado ocurrió en 168 casos; de estos, 31 mujeres se sometieron a la amputación cónica, 104 a cirugías de alta frecuencia, nueve a histerectomías y 24 recibieron conducta conservadora. Entre las mujeres con lesión de alto grado y tratadas de forma conservadora, ocho (33,3% reincidieron, mientras que de las sometidas a la conducta no conservadora, diez (6,9% reincidieron, siendo esta diferencia estadísticamente significativa (p=0,0009, RP=4,8 (IC95% 2,11;10,93. En aquellas que hicieron seguimiento clínico-citológico, tres (30,0% y, entre las cauterizadas, cinco (35,7% reincidieron en el plazo de tres años, sin diferencia significativa (p=0,5611. La reincidencia por debajo y por encima de los 30 años ocurrió, respectivamente, en siete (13,8% y 11 (12,2% mujeres (p=0,9955. CONCLUSIONES: La edad de la mujer no influencia el pronóstico de la reincidencia. El tratamiento conservador debe ser indicado como conducta de excepción, dada la alta tasa de reincidencia, y el seguimiento debe ser riguroso, con acompañamiento citológico y colposcópico por inclusive tres años, período en el que ocurre la mayoría de las reincidencias.OBJECTIVE: To assess the association between conservative management of high-grade cervical squamous intraepithelial lesions and recurrence rates and age groups. METHODS: Cross-sectional, retrospective, analytical observational study of 509 women (aged 15 to 76 with abnormal Pap smears attending a public reference

  6. Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

    Science.gov (United States)

    Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

    2016-02-01

    Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

  7. Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

    International Nuclear Information System (INIS)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

    2008-01-01

    Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

  8. The clinical efficacy of consolidation chemotherapy for resectable esophageal squamous cell cancer after trimodality therapy.

    Science.gov (United States)

    Sun, Yanan; Cheng, Siguo; Lu, Yufei; Zheng, Xiaoli; Ye, Ke; Ge, Hong

    2016-01-01

    We aimed to assess the clinical outcome of consolidation chemotherapy for resectable esophageal squamous cell cancer (ESCC) after trimodality therapy. From January 2005 to December 2012, a total of 192 consecutive locally advanced ESCC patients who underwent trimodality therapy successfully was included. Grouping was based on the degree of myelosuppression occurred during preoperative chemoradiotherapy. Of the 192 patients, 120 patients underwent trimodality therapy only (TT group), while 72 patients received consolidation chemotherapy additionally after trimodality therapy (TC group). Preoperative chemoradiotherapy included two cycles of chemotherapy concurrently with radiotherapy. The chemotherapy regimen consisted of cisplatin 20 mg/m2/day and fluorouracil 400 mg/m2/day administered intravenously infusion on days 1-5 of a 21 days cycle. Concurrent radiotherapy was delivered in a total of 40 Gy in 20 fractions. All patients underwent surgery successfully. For 72 patients in TC group, additional 1-4 cycles of consolidation chemotherapy were administered, and chemotherapy regimen was as before. The 5-year survival rate was 43.5% in TT group, as compared with 48.8% in TC group. (P = 0.238). The 5.year progression.free survival. (PFS) rates were 34.0% in TT group and 38.8% in TC group. (P = 0.049). Risk reduction in PFS was remarkable for males and those who did not achieve pathologic complete response. (pCR). The incidence rate of disease progression did not differ significantly. (P = 0.200). The addition of consolidation chemotherapy demonstrates no survival benefit for patients with locally advanced ESCC, but PFS is significantly improved, especially for males and those who did not achieve pCR.

  9. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  10. Efficacy of icotinib in lung squamous-cell cancer: A real-world experience from single institution.

    Science.gov (United States)

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2017-12-01

    Squamous cell carcinoma is a less common type of nonsmall cell lung cancer (NSCLC) which associates with a poor clinical prognosis and lacks specific therapy. This study aimed to evaluate the efficacy and safety of icotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has proven to be effective in EGFR-mutated NSCLC, in patients with lung squamous-cell cancer. Retrospective analysis was conducted in patients who had advanced lung squamous-cell cancer confirmed by cytology or histology. Patients were treated orally with icotinib (125 mg, three times daily) until event of unacceptable toxicity, disease progression or death. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, overall response rate and disease control rate. Between January 2014 and May 2016, 20 patients were enrolled and evaluated for the efficacy and safety of icotinib. Overall, the median overall survival and progression-free survival were 9.93 months (95% confidence interval (CI): 3.46-16.40) and 3.0 months (95% CI: 0.00-8.35), respectively. The overall response rate and disease control rate were 20% and 70%, respectively. For treatment-naive patients (n = 11), the overall survival and progression-free survival were 9.93 months (95% CI: 0.00-23.49) and 6.27 months (95% CI: 0.00-12.61); the response rate and disease control rate were 27.3% and 54.5%, respectively. The overall survival and progression-free survival of patients treated with second- or multiple-line icotinib treatment (n = 9) were 6.5 months (95% CI: 0.80-12.20) and 1.2 months (95% CI: 1.10-1.30). A total of 11 patients experienced at least one treatment-related adverse event, most of which were mild to moderate. The most common manifestations were rash (n = 6, 30%) followed by diarrhea (n = 2, 10%). Icotinib has demonstrated a favorable efficacy and safety profile in patients with advanced lung squamous-cell cancer. © 2017 John Wiley & Sons Australia, Ltd.

  11. Risk Factors for Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Estrella de la Caridad Armenteros Espino

    2016-09-01

    Full Text Available Background: cervix cancer constitutes the second cause of death worldwide, with new diagnosis each year. Objective: to determine the risk factors of cervical intraepithelial neoplasia in the municipality of Cruces. Methods: it was developed an analytical research with case and control design from November 2013 to November 2014. The group of cases was formed of the 34 women with this diagnosis. There were selected 64 females from the same environment with the same age for the control group. The data obtained by surveys and clinical records reviews were presented in absolute numbers and percentages. It was used Chi-squared test and odd ratio. Results: 52 % of women with neoplasia were less than 25 years old. Significant differences were found which associate neoplasia with early sexual intercourse, sexually transmitted infections by Papilloma virus, Plane genital condyloma, and the use of oral contraceptive pills. Multiple sex partner was a frequent antecedent. Conclusion: risk factors associated to cervical intraepithelial neoplasia in the group of women studied in the Cruces municipality were early sexual intercourse, mainly before 15 years old, multiple sex partner, sexually communicated diseases and the use of oral contraceptive pills for more than 5 years.

  12. Long term results of primary radiation therapy for squamous cancer of the base of tongue

    International Nuclear Information System (INIS)

    Harrison, LB; Lee, H; Kraus, DH; Zelefsky, M; Strong, EW; Pfister, DG; Raben, A; Shah, J; White, C; Carper, E; Portenoy, R

    1996-01-01

    From 1981-1995, 68 patients with primary squamous cell cancer of the base of tongue were managed with primary radiation therapy, with neck dissection added for those who presented with palpable lymph node metastases. Ages ranged from 35-77 (median 55). There were 59 males and 9 females. T Stage was: T1-17, T2-32, T3-17, T4-2. Fifty-eight patients (85%) presented with nodal metastases. Treatment generally involved external beam radiation (EBRT) to the primary site and upper neck (54 Gy), low neck (50 Gy), additional EBRT to area of nodal involvement to 60 Gy, followed (2-4 weeks later) by brachytherapy boost (20-30 Gy) to the base of tongue using Iridium-192. The implant was done at the same anesthesia as the neck dissection, and all patients had temporary tracheostomy. Follow-up ranges from 1-151 months (median 36 months). Nine patients received neo-adjuvant chemotherapy. Actuarial 5 and 10-year local control is 88% and 88%, regional control is 96% and 96%, distant metastasis free survival is 91% and 76%, disease free survival is 80% and 67%, and overall survival is 86% and 52%, respectively. After EBRT, 78% of dissected necks were pathologically negative. Complications occurred in 16%. A detailed quality of life (QOL) assessment has been completed on the first 36 patients with a minimum follow-up of 3 years, and median follow-up of 5 years. This included a Performance Status Assessment, socio-demographic and economic questionnaire, a multidimensional QOL assessment measuring emotional, physical, social and functional well-being, and the Memorial Symptom Assessment Scale. This data will be presented. The overwhelming majority of patients were able to maintain their pre-diagnosis earning potential, employment status, speaking ability and ability to eat in public. However, a variety of symptoms such as xerostomia, swallowing difficulty, decreased energy, changes in taste and dietary restrictions were observed. Our data shows that primary radiation therapy produces

  13. Necitumumab in Metastatic Squamous Cell Lung Cancer: Establishing a Value-Based Cost.

    Science.gov (United States)

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; Ramalingam, Suresh S; Khuri, Fadlo R; Flowers, Christopher R

    2015-12-01

    The SQUIRE trial demonstrated that adding necitumumab to chemotherapy for patients with metastatic squamous cell lung cancer (mSqCLC) increased median overall survival by 1.6 months (hazard ratio, 0.84). However, the costs and value associated with this intervention remains unclear. Value-based pricing links the price of a drug to the benefit that it provides and is a novel method to establish prices for new treatments. To evaluate the range of drug costs for which adding necitumumab to chemotherapy could be considered cost-effective. We developed a Markov model using data from multiple sources, including the SQUIRE trial, which compared standard chemotherapy with and without necitumumab as first-line treatment of mSqCLC, to evaluate the costs and patient life expectancies associated with each regimen. In the analysis, patients were modeled to receive gemcitabine and cisplatin for 6 cycles or gemcitabine, cisplatin, and necitumumab for 6 cycles followed by maintenance necitumumab. Our model's clinical inputs were the survival estimates and frequency of adverse events (AEs) described in the SQUIRE trial. Log-logistic models were fitted to the survival distributions in the SQUIRE trial. The cost inputs included drug costs, based on the Medicare average sale prices, and costs for drug administration and management of AEs, based on Medicare reimbursement rates (all in 2014 US dollars). We evaluated incremental cost-effectiveness ratios (ICERs) for the use of necitumumab across a range of values for its cost. Model robustness was assessed by probabilistic sensitivity analyses, based on 10 000 Monte Carlo simulations, sampling values from the distributions of all model parameters. In the base case analysis, the addition of necitumumab to the treatment regimen produced an incremental survival benefit of 0.15 life-years and 0.11 quality-adjusted life-years (QALYs). The probabilistic sensitivity analyses established that when necitumumab cost less than $563 and less than

  14. Epidemiology of Cervical Squamous Intraepithelial Lesions in HIV ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Kenya. A cross sectional study was conducted in a hospital in Central Kenya, Kiambu district. The study ... were widowed. About 642 (92.6%) of the HIV infected women were in follow-up period of ≥ 1 year. ... Although some studies suggest.

  15. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

    International Nuclear Information System (INIS)

    Anagnostou, Valsamo K; Boffa, Daniel; Gettinger, Scott; Detterbeck, Frank; Homer, Robert J; Dougenis, Dimitrios; Rimm, David L; Syrigos, Konstantinos N; Lowery, Frank J; Zolota, Vassiliki; Tzelepi, Vassiliki; Gopinath, Arun; Liceaga, Camil; Panagopoulos, Nikolaos; Frangia, Konstantina; Tanoue, Lynn

    2010-01-01

    Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA ® , a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients

  16. Serous tubal intraepithelial neoplasia: the concept and its application.

    Science.gov (United States)

    Meserve, Emily E K; Brouwer, Jan; Crum, Christopher P

    2017-05-01

    In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that include both serous tubal epithelial proliferations (or lesions) of uncertain significance and serous tubal intraepithelial carcinomas. These precursors can be considered from three perspectives. The first is biologic underpinnings, which are multifactorial, and include the intersection of DNA damage with Tp53 mutations and disturbances in transcriptional regulation that increase with age. The second perspective is the morphologic discovery and classification of intraepithelial neoplasms that are intercepted early in their natural history, either incidentally or in risk-reduction surgeries for germline mutations. For the practicing pathologist, as well as the investigators, a distinction between a primary intraepithelial neoplasm and an intramucosal carcinoma must be made to avoid misinterpreting (or underestimating) the significance of these proliferations. The third perspective is the application of this information to intervention, devising strategies that will actually lower the ovarian cancer death rate by opportunistic salpingectomy, widespread comprehensive genetic screening and early detection. Central to this issue are the questions of (1) whether some STICs are metastatic, (2) whether lower-grade epithelial proliferations can invade prior to evolving into intraepithelial carcinoma, or (3) metastasize and become malignant elsewhere ('precursor escape'). An important caveat is the persistent and unsettling reality that many high-grade serous carcinomas are not associated with an obvious point of initiation in the fallopian tube. The pathologist sits squarely in the midst of all of these issues, and has a pivotal role in managing expectations for stemming the death

  17. EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Kodali Venkataramana

    2017-03-01

    Full Text Available BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelial neoplasia. MATERIALS AND METHODS It is a prospective study for a period of two years. 50 cases of cervical intraepithelial neoplasia of various grades on histopathology were included in the study. Polymerase chain reaction DNA sequencing was done in all the cases. The patients were followed up for 1 year with Pap smears and results tabulated. RESULTS 77.77% of cases were human papilloma virus 16 positive and 22.22% for human papilloma virus 18. High-risk human papilloma virus was positive in 66.66% of cases beyond 30 years of age. In cases with positive HPV 16 or 18, 62.5% of CIN 1 cases progressed to CIN 2 on follow up for one year,all the CIN2 cases progressed to CIN 3 and CIN 3 cases persisted in the same phase. CONCLUSION High-risk human papilloma virus testing beyond 30 years should be included in the screening test along with Pap smears.

  18. A randomized trial of chest irradiation alone versus chest irradiation plus Lentinan in squamous cell lung cancer in limited stage

    International Nuclear Information System (INIS)

    Kimura, Ikuro; Ohnoshi, Taisuke; Konno, Kiyoshi

    1993-01-01

    In an attempt to evaluate the effect of Lentinan, polysaccharides from Lentinusedodes, in combination with chest irradiation for limited-stage squamous cell lung cancer, we conducted a randomized trial between January 1987 and July 1989. Patients were randomly allocated to receive either a definitive chest irradiation of 60 Gy alone (RT) or the chest irradiation plus Lentinan (RT+L). Patients allocated to the RT+L group received iv infusion of Lentinan, 1 mg twice a week or 2 mg once a week, as long as possible. Of 201 patients enrolled, 183 (94 for RT, and 89 for RT+L) were eligible for analysis of survival time, and 169 (86 for RT, and 83 for RT+L) were evaluated for tumor response, survival time and quality of life. The response rate to the treatments showed a trend favoring the RT+L group (65% vs. 51%, p=0.142). The median survival time was 455 days for the RT+L group and 371 days for the RT group. The difference was not statistically significant. In the subset of patients with cancer of hilar origin, however, RT+L group patients lived significantly longer than RT group patients: Progression-free interval from symptoms and quality of life were evaluated for the both groups based on manual records of an individual patient. RT+L group patients had a significantly longer progression-free interval from dyspneic feeling than the RT group patients. The RT+L group tended to have a feeling of well-being. We conclude that Lentinan in combination with chest irradiation is useful for patients with limited-stage squamous cell lung cancer in terms of prolongation of life and maintenance of a favorable quality of life as well. (author)

  19. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  20. Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey

    Science.gov (United States)

    He, Z; Zhao, Y; Guo, C; Liu, Y; Sun, M; Liu, F; Wang, X; Guo, F; Chen, K; Gao, L; Ning, T; Pan, Y; Li, Y; Zhang, S; Lu, C; Wang, Z; Cai, H; Ke, Y

    2010-01-01

    Background: The etiology of esophageal squamous cell cancer (ESCC) in high prevalence regions of China remains unclear. Methods: Endoscopic biopsies were conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China. Results: In this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma in situ and invasive ESCC. Using deep well (depth >100 meters) as water source (odds ratio=0.72, 95% confidence interval: 0.54–0.96) was negatively associated with ESCC and its precursors, whereas tobacco and alcohol use were not significantly associated with ESCC. Conclusions: Water source and other factors in this region need further evaluation by longitudinal studies. PMID:20700119

  1. Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

    Science.gov (United States)

    Balacescu, Ovidiu; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica

    2014-04-08

    Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the

  2. Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure

    International Nuclear Information System (INIS)

    Balacescu, Ovidiu; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura

    2014-01-01

    Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient’s 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. ‘DNA Replication, Recombination and Repair’ represented one of the most important mechanisms activated in non-responsive cervical tumors, and the ‘Role of BRCA1 in DNA Damage Response’ was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information

  3. Nivolumab-induced synchronous occurrence of myositis and hypothyroidism in a patient with squamous cell lung cancer.

    Science.gov (United States)

    Badovinac, Sonja; Korsic, Marta; Zarkovic, Kamelija; Mursic, Davorka; Roglic, Mihovil; Jakopovic, Marko; Samarzija, Miroslav

    2018-03-01

    Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities. During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism. Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

  4. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

    International Nuclear Information System (INIS)

    Zhang, Jian; Gong, Youling; Peng, Feng; Li, Na; Liu, Yongmei; Xu, Yong; Zhou, Lin; Wang, Jin; Zhu, Jiang; Huang, Meijuan

    2012-01-01

    To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group). The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study. For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome

  5. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

    Directory of Open Access Journals (Sweden)

    Zhang Jian

    2012-06-01

    Full Text Available Abstract Purpose To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. Methods 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy combined with chemotherapy consisting of either 5-fluorouracil (5-FU plus cisplatin (DDP (R-FP group or paclitaxel plus DDP (R-TP group. Results The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS and overall survival (OS time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months in the R-TP group was superior to that in the R-FP group (median: 9.8 months (p = 0.012. Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months and OS (16.3 months were significantly superior to the PFS (8.7 months and OS (11.3 months among those patients did not (all p  Conclusions For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome.

  6. Identification of cancer stem-like side population cells in purified primary cultured human laryngeal squamous cell carcinoma epithelia.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Wu

    Full Text Available Cancer stem-like side population (SP cells have been identified in many solid tumors; however, most of these investigations are performed using established cancer cell lines. Cancer cells in tumor tissue containing fibroblasts and many other types of cells are much more complex than any cancer cell line. Although SP cells were identified in the laryngeal squamous cell carcinoma (LSCC cell line Hep-2 in our pilot study, it is unknown whether the LSCC tissue contains SP cells. In this study, LSCC cells (LSCCs were primary cultured and purified from a surgically resected LSCC specimen derived from a well-differentiated epiglottic neoplasm of a Chinese male. This was followed by the verification of epithelium-specific characteristics, such as ultrastructure and biomarkers. A distinct SP subpopulation (4.45±1.07% was isolated by Hoechst 33342 efflux analysis from cultured LSCCs by using a flow cytometer. Cancer stem cell (CSC-associated assays, including expression of self-renewal and CSC marker genes, proliferation, differentiation, spheroid formation, chemotherapy resistance, and tumorigenicity were then conducted between SP and non-SP (NSP LSCCs. In vitro and in vivo assays revealed that SP cells manifested preferential expression of self-renewal and CSC marker genes, higher capacity for proliferation, differentiation, and spheroid formation; enhanced resistance to chemotherapy; and greater xenograft tumorigenicity in immunodeficient mice compared with NSP cells. These findings suggest that the primary cultured and purified LSCCs contain cancer stem-like SP cells, which may serve as a valuable model for CSC research in LSCC.

  7. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    Science.gov (United States)

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  8. Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells.

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    J Dinesh Kumar

    Full Text Available Stromal cells such as myofibroblasts influence tumor progression. The mechanisms are unclear but may involve effects on both tumor cells and recruitment of bone marrow-derived mesenchymal stromal cells (MSCs which then colonize tumors. Using iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as overexpressed in esophageal squamous cancer associated myofibroblasts (CAMs compared with adjacent tissue myofibroblasts (ATMs. The chemerin receptor, ChemR23, is expressed by MSCs. Conditioned media (CM from CAMs significantly increased MSC cell migration compared to ATM-CM; the action of CAM-CM was significantly reduced by chemerin-neutralising antibody, pretreatment of CAMs with chemerin siRNA, pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 receptor antagonist, CCX832. Stimulation of MSCs by chemerin increased phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases and PKC reversed chemerin-stimulated MSC migration. Chemerin stimulation of MSCs also induced expression and secretion of macrophage inhibitory factor (MIF that tended to restrict migratory responses to low concentrations of chemerin but not higher concentrations. In a xenograft model consisting of OE21 esophageal cancer cells and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus, chemerin secreted from esophageal cancer myofibroblasts is a potential chemoattractant for MSCs and its inhibition may delay tumor progression.

  9. CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ke-Fei He

    2014-01-01

    Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

  10. Functional Genomics Uncover the Biology behind the Responsiveness of Head and Neck Squamous Cell Cancer Patients to Cetuximab.

    Science.gov (United States)

    Bossi, Paolo; Bergamini, Cristiana; Siano, Marco; Cossu Rocca, Maria; Sponghini, Andrea P; Favales, Federica; Giannoccaro, Marco; Marchesi, Edoardo; Cortelazzi, Barbara; Perrone, Federica; Pilotti, Silvana; Locati, Laura D; Licitra, Lisa; Canevari, Silvana; De Cecco, Loris

    2016-08-01

    To identify the tumor portrait of the minority of head and neck squamous cell carcinoma (HNSCC) patients with recurrent-metastatic (RM) disease who upon treatment with platinum-based chemotherapy plus cetuximab present a long-lasting response. The gene expression of pretreatment samples from 40 HNSCC-RM patients, divided in two groups [14 long-progression-free survival (PFS) and 26 short-PFS (median = 19 and 3 months, respectively)], was associated with PFS and was challenged against a dataset from metastatic colon cancer patients treated with cetuximab. For biologic analysis, we performed functional and subtype association using gene set enrichment analysis, associated biology across all currently available HNSCC signatures, and inferred drug sensitivity using data from the Cancer Genomic Project. The identified genomic profile exhibited a significant predictive value that was essentially confirmed in the single publicly available dataset of cetuximab-treated patients. The main divergence between long- and short-PFS groups was based on developmental/differentiation status. The long-PFS patients are characterized by basal subtype traits such as strong EGFR signaling phenotype and hypoxic differentiation, further validated by the significantly higher association with the hypoxia metagene. The short-PFS patients presented a strong activation of RAS signaling confirmed in an in vitro model of two isogenic HNSCC cell lines sensitive or resistant to cetuximab. The predicted drug sensitivity for all four EGFR inhibitors was higher in long- versus short-PFS patients (P range: biology behind response to platinum-based chemotherapy plus cetuximab in RM-HNSCC cancer and may have translational implications improving treatment selection. Clin Cancer Res; 22(15); 3961-70. ©2016 AACRSee related commentary by Chau and Hammerman, p. 3710. ©2016 American Association for Cancer Research.

  11. [Effect of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes].

    Science.gov (United States)

    Chen, Wei-qiang; Feng, Feng-lan; Gu, Hong-biao; Pan, De-shun

    2010-07-01

    To examine the effects of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes. The inhibition effects of sodium phenylbutyrate on Tca8113 and human tongue squamous cell carcinoma (TCSSA) cell lines were detected by methyl thiazoly terazolium (MTT) and the apoptosis of the cancer cells after being induced by sodium phenylbutyrate examined by flow cytometry (FCM). The expression of p21 and survivin genes were observed with Western blotting and RT-PCR. Compared with control group, the level of p21 mRNA and protein of Tca8113 cellline increased to 0.09 ± 0.08 and increased 0.72 ± 0.10, that of TCSSA cellline increased 1.34 ± 0.12 and 1.56 ± 0.09 (P Sodium phenylbutyrate inhibited the cell proliferation, promoted cell apoptosis and arrested the cells in G₁/G₀ phase. The amount of p21 mRNA and protein were increased, and the expression of survivin gene was decreased. Sodium phenylbutyrate exhibited remarkable inhibitory effects on human tongue squamous cancer cell proliferation and induced cancer cell apoptosis. The mechanism may be due to up-regulation of p21 gene and down-regulation of survivin gene. The mRNA level of p21 gene and survivin gene showed a strong correlation.

  12. Health-Related Quality of Life and Sexual Functioning of HIV-Positive Men Who Have Sex With Men Who Are Treated for Anal Intraepithelial Neoplasia

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, Matthijs L.; Richel, Olivier; Nieuwkerk, Pythia T.; de Vries, Henry J. C.; Prins, Jan M.

    2016-01-01

    The impact of the treatment of precursor lesions of anal cancer (anal intraepithelial neoplasia) on health-related quality of life has not been investigated. This study aimed to evaluate the impact of 3 treatment options for anal intraepithelial neoplasia on health-related quality of life and sexual

  13. Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro, Brazil.

    Directory of Open Access Journals (Sweden)

    Angela Cristina Vasconcelos de Andrade

    Full Text Available INTRODUCTION: Despite the availability of preventive strategies (screening tests and vaccines, cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV and thus development of cervical squamous intraepithelial neoplasia (CIN. METHODS: Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ. At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. RESULTS: The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28-41 years. The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥ 35 years (aPR  =  3.22 95%CI 1.23-8.39, current tobacco use (aPR  =  3.69 95%CI 1.54-8.78, nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50-24.3 and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99-7.24. DISCUSSION: Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical

  14. Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium.

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    Usha Malhotra

    Full Text Available Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC and/or cancer-adjacent squamous epithelium (CASE. The purpose of this study was 1 to determine the degree of survivin up regulation in samples of EAC and CASE, 2 to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3 to examine the effect of survivin inhibition on apoptosis in EAC cells.Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome.Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis.Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker.

  15. Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma.

    Science.gov (United States)

    Montoro, José Raphael de Moura Campos; Mamede, Rui Celso Martins; Neder Serafini, Luciano; Saggioro, Fabiano Pinto; Figueiredo, David Livingstone Alves; Silva, Wilson Araújo da; Jungbluth, Achim A; Spagnoli, Giulio Cesare; Zago, Marco Antônio

    2012-08-01

    Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. Copyright © 2011 Wiley Periodicals, Inc.

  16. Oral sex and human papilloma virus-related head and neck squamous cell cancer: a review of the literature.

    Science.gov (United States)

    Shah, Ankit; Malik, Akshat; Garg, Apurva; Mair, Manish; Nair, Sudhir; Chaturvedi, Pankaj

    2017-11-01

    Head neck squamous cell carcinomas (HNSCCs) are a significant cause of morbidity and mortality all around the world. Just like tobacco and alcohol, Human papilloma virus (HPV) infection is now recognized to play a role in the pathogenesis of a subset of HNSCCs. Unprotected sexual behaviours with the HPV carrier plays an important role in transmission of this virus. The global incidence of head and neck cancers is declining, but the incidence of HPV related head and neck cancers is rapidly increasing over the last few decades. However, most institutions do not mandate documentation of sexual history or counselling of patients regarding sexual practices like they do for tobacco and alcohol addictions in HNSCC patients. The aim of this review of literature is to analyse if there is a strong evidence to correlate oral sex with HPV related HNSCC and counsel the patient's regarding sexual behaviours. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Two Unusual Cases of Oral Lichen Planus Arising After Oral Squamous Cell Carcinoma: Can Oral Cancer Trigger Autoimmunity?

    Science.gov (United States)

    Gissi, Davide Bartolomeo; Asioli, Sofia; Gabusi, Andrea

    2017-08-01

    Autoimmune diseases occur when the immune system fails to recognize self-antigens expressed on the body's own cells and attacks them. Oral lichen planus (OLP) is a chronic autoimmune mucocutaneous disease of the oral cavity characterized by white/red lesions. Considered a potentially malignant disorder, OLP evolution into oral squamous cell carcinoma (OSCC) is still a matter of debate. While chronic autoimmune inflammation is considered a potential risk factor for malignant transformation in many solid tumors, the opposite idea that cancer may trigger autoimmune responses remains controversial. We describe 2 patients who developed lesions clinically suggestive of OLP with histological evidence of lichenoid infiltration some time after OSCC removal, even in areas far from the neoplastic site. Neither patient had OLP before the diagnosis of OSCC, or reported exposure to OLP-associated etiologic factors, and neither. experienced tumor recurrence during follow-up. Our findings suggest that oral cancer remission may be linked to OLP development, but further studies are necessary to unveil the underlying mechanisms and possible prognostic implications.

  18. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

    Science.gov (United States)

    2011-01-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent. PMID:21299897

  19. Anti-Cancer Effects of Imperata cylindrica Leaf Extract on Human Oral Squamous Carcinoma Cell Line SCC-9 in Vitro.

    Science.gov (United States)

    Keshava, Rohini; Muniyappa, Nagesh; Gope, Rajalakshmi; Ramaswamaiah, Ananthanarayana Saligrama

    2016-01-01

    Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.

  20. Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Horn, L.C.; Reichert, A.; Oster, A.

    2008-01-01

    The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is...... immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology Udgivelsesdato: 2008/4......The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides......) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch...

  1. A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer

    Directory of Open Access Journals (Sweden)

    Athanasios Fountas

    2018-04-01

    Full Text Available Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1 and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed.

  2. Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer

    Directory of Open Access Journals (Sweden)

    Swapp Aaron

    2007-06-01

    Full Text Available Abstract Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC to proanthocyanidin (PAC, a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be

  3. Swainsonine promotes apoptosis in human oesophageal squamous ...

    Indian Academy of Sciences (India)

    2012-10-24

    Oct 24, 2012 ... oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine ..... sical death receptor-mediated apoptotic pathway while ..... hormone-resistant prostate cancer PC-3 cells. Cancer ...

  4. Screening frequency and atypical cells and the prediction of cervical cancer risk.

    Science.gov (United States)

    Chen, Yun-Yuan; You, San-Lin; Koong, Shin-Lan; Liu, Jessica; Chen, Chi-An; Chen, Chien-Jen

    2014-05-01

    To evaluate the screening efficacy and importance of atypical squamous cells and atypical glandular cells in predicting subsequent cervical cancer risk. This national cohort study in Taiwan analyzed associations between Pap test screening frequency and findings in 1995-2000 and subsequent risk of squamous cell carcinoma and adenocarcinoma after 2002. Women aged 30 years or older in 1995 without a cervical cancer history were included. Multivariate-adjusted hazard ratios and their 95% confidence intervals (CIs) were assessed using Cox regression analysis. During a total follow-up of 31,693,980 person-years in 2002-2008, 9,471 squamous cell carcinoma and 1,455 adenocarcinoma cases were newly diagnosed, resulting in 2,067 deaths. The risk of developing and dying from squamous cell carcinoma decreased significantly with increasing attendance frequency between 1995 and 2000 (all P values for trend1995-2000 had 0.69-fold and 0.35-fold decrease in incidence and mortality of adenocarcinoma, respectively, compared with women who never attended any screenings. Abnormal cytologic findings were significant predictors of the incidence and mortality of cervical cancers. The adjusted hazard ratio (95% CI) of developing squamous cell carcinoma was 29.94 (22.83-39.25) for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions, and the adjusted hazard ratio (95% CI) of developing adenocarcinoma was 49.43 (36.49-66.97) for atypical glandular cells. Significant reductions in cervical adenocarcinoma occurred in women who attend three or more annual screenings in 6 years. High-grade atypical squamous cells and atypical glandular cells are important predictors of subsequent adenocarcinoma and squamous cell carcinoma. II.

  5. Next Generation Sequencing of Tubal Intraepithelial Carcinomas

    Science.gov (United States)

    McDaniel, Andrew S.; Stall, Jennifer N.; Hovelson, Daniel H.; Cani, Andi K.; Liu, Chia-Jen; Tomlins, Scott A.; Cho, Kathleen R.

    2016-01-01

    Importance High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs or more specifically STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. Observations We performed targeted next generation sequencing (NGS) on formalin-fixed, paraffin- embedded tissue from four women, two with HGSC and two with uterine endometrioid carcinoma (UEC) who were diagnosed with synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal relationship between these lesions. NGS confirmed the presence of a STIC clonally unrelated to one case of UEC. NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. Conclusions and Relevance We demonstrate that targeted NGS can identify genetic lesions in minute lesions such as TICs, and confirm TP53 mutations as early driving events for HGSC. NGS also demonstrated unexpected relationships between presumed STICs and synchronous carcinomas, suggesting potential diagnostic and translational research applications. PMID:26181193

  6. MicroRNA expression profiles of cancer stem cells in head and neck squamous cell carcinoma

    OpenAIRE

    YATA, KAZUYA; BEDER, LEVENT BEKIR; TAMAGAWA, SHUNJI; HOTOMI, MUNEKI; HIROHASHI, YOSHIHIKO; GRENMAN, REIDAR; YAMANAKA, NOBORU

    2015-01-01

    Increasing evidence indicates that cancer stem cells have essential roles in tumor initiation, progression, metastasis and resistance to chemo-radiation. Recent research has pointed out biological importance of microRNAs in cancer stem cell dysregulation. Total number of mature microRNAs in human genome increased to more than 2,500 with the recent up-date of the database. However, currently no information is available regarding microRNA expression profiles of cancer stem cells in head and nec...

  7. A comparison of the direct medical costs for individuals with or without basal or squamous cell skin cancer: A study from Australia

    Directory of Open Access Journals (Sweden)

    David Rowell

    2016-05-01

    Full Text Available Objectives: The composition of the medical costs incurred by people treated for basal cell and squamous cell carcinomas (hereafter keratinocyte cancers is not adequately understood. We sought to compare the medical costs of individuals with or without keratinocyte cancers. Methods: We used national health insurance data to analyze the direct medical costs of 2000 cases and 2000 controls nested within the QSkin prospective cohort study (n = 43,794 conducted in Australia. We reconstructed the medical history of patients using medical and pharmaceutical item codes and then compared the health service costs of individuals treated for keratinocyte cancers with those not treated for keratinocyte cancers. Results: Individuals treated for keratinocyte cancers consumed on average AUD$1320 per annum more in medical services than those without keratinocyte cancers. Only 23.2% of costs were attributed to the explicit treatment of keratinocyte cancers. The principal drivers of the residual costs were medical attendances, surgical procedures on the skin, and histopathology services. We found significant positive associations between history of treatment for keratinocyte cancers with treatments for other health conditions, including melanoma, cardiovascular disease, lipidemia, osteoporosis, rheumatoid arthritis, colorectal cancer, prostate cancer, and tuberculosis. Conclusion: Individuals treated for keratinocyte cancers have substantially higher medical costs overall than individuals without keratinocyte cancers. The direct costs of skin cancer excision account for only one-fifth of this difference.

  8. miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Jiong; Lin, Yao [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Fan, Li [Department of Pharmaceutical Analysis, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shaanxi, 710032 (China); Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055 (China); Kuang, Wei [Department of Stomatology, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, 510010 (China); Zheng, Liwei [State Key Laboratory of Oral Diseases, Sichuan University, Wuhou District, Chengdu, 610041 (China); Wu, Jiahua [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Shang, Peng [Patient-specific Orthopedic Technology Research Center in GuangDong Research Centre for Neural Engineering, 1068 Xueyuan Boulevard, University Town of Shenzhen, Xili, Nanshan, Shenzhen, 518055 (China); Wang, Qiaofeng [Department of Pharmaceutical Chemistry, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shanxi, 710032 (China); Tan, Jiali, E-mail: jasminenov@163.com [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China)

    2016-04-29

    Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3′UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC. - Highlights: • Much lower miR-203 expression in cisplatin resistant Tca8113 cells is discovered. • Delivery of miR-203 can sensitize the Tca8113 cells to cisplatin induced cell death. • MiR-203 can downregulate PIK3CA through the 3′UTR. • The effects of miR-203 on cisplatin sensitivity is mainly through PIK3CA pathway.

  9. Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings

    NARCIS (Netherlands)

    Yang, Nan; Eijsink, Jasper J. H.; Lendvai, Agnes; Volders, Haukeline H.; Klip, Harry; Buikema, Henk J.; van Hemel, Bettien M.; Schuuring, Ed; van der Zee, Ate G. J.; Wisman, G. Bea A.

    2009-01-01

    Purpose: Recently, we reported 13 possible cervical cancer-specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these

  10. Methylation Markers for CCNA1 and C13ORF18 Are Strongly Associated with High-Grade Cervical Intraepithelial Neoplasia and Cervical Cancer in Cervical Scrapings

    NARCIS (Netherlands)

    Yang, Nan; Eijsink, Jasper J. H.; Lendvai, Agnes; Volders, Haukeline H.; Klip, Harry; Buikema, Henk J.; van Hemel, Bettien M.; Schuuring, Ed; van der Zee, Ate G. J.; Wisman, G. Bea A.

    Purpose: Recently, we reported 13 possible cervical cancer-specific methylated biomarkers identified by pharmacologic unmasking microarray in combination with large-genome computational screening. The aim of the present study was to perform an in-depth analysis of the methylation patterns of these

  11. Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population

    Directory of Open Access Journals (Sweden)

    McIntyre James A

    2008-07-01

    Full Text Available Abstract Background In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN, the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ. Methods Women with high grade squamous intraepithelial lesions or worse (HSIL, less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression Results The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear. Conclusion We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.

  12. A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer.

    Science.gov (United States)

    Fountas, Athanasios; Chai, Shu Teng; Ayuk, John; Gittoes, Neil; Chavda, Swarupsinh; Karavitaki, Niki

    2018-01-01

    Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed. Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.Meticulous review of unexpected

  13. AKT1 loss correlates with episomal HPV16 in vulval intraepithelial neoplasia.

    Directory of Open Access Journals (Sweden)

    Arucha L Ekeowa-Anderson

    Full Text Available Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV, particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma- PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN and vulval squamous cell carcinoma (vSCC. We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.

  14. Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression

    International Nuclear Information System (INIS)

    Jouppila-Mättö, Anna; Närkiö-Mäkelä, Mervi; Soini, Ylermi; Pukkila, Matti; Sironen, Reijo; Tuhkanen, Hanna; Mannermaa, Arto; Kosma, Veli-Matti

    2011-01-01

    Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT. Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas. Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively). TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome

  15. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

    Science.gov (United States)

    Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

    2017-08-01

    We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

  16. Plasma proteome analysis of cervical intraepithelial neoplasia and ...

    Indian Academy of Sciences (India)

    Prakash

    cancer will contribute to an understanding of how the disease develops and progresses. ... grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel .... centrifugation at 800xg for 10 min at 4°C and kept in aliquots ..... reveals differential expression of vitamin D binding protein;.

  17. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

    2018-03-02

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

  18. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

    2018-01-01

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

  19. Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma

    Science.gov (United States)

    Zolkind, Paul; Przybylski, Dariusz; Marjanovic, Nemanja; Nguyen, Lan; Lin, Tianxiang; Johanns, Tanner; Alexandrov, Anton; Zhou, Liye; Allen, Clint T.; Miceli, Alexander P.; Schreiber, Robert D.; Artyomov, Maxim; Dunn, Gavin P.; Uppaluri, Ravindra

    2018-01-01

    Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines. Here, we aimed to define a platform for checkpoint and other immunotherapy studies using syngeneic HNSCC cell line models (MOC2 and MOC22), and evaluated the association between mutation burden, predicted neoantigen landscape, infiltrating T cell populations and responsiveness of tumors to anti-PD1 therapy. We defined dramatic hematopoietic cell transcriptomic alterations in the MOC22 anti-PD1 responsive model in both tumor and draining lymph nodes. Using a cancer immunogenomics pipeline and validation with ELISPOT and tetramer analysis, we identified the H-2Kb-restricted ICAM1P315L (mICAM1) as a neoantigen in MOC22. Finally, we demonstrated that mICAM1 vaccination was able to protect against MOC22 tumor development defining mICAM1 as a bona fide neoantigen. Together these data define a pre-clinical HNSCC model system that provides a foundation for future investigations into combination and novel therapeutics. PMID:29423108

  20. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    Science.gov (United States)

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  1. Photochemotherapy - psoralens + UV-A(PUVA) - does it increase the risk for cancer?

    International Nuclear Information System (INIS)

    Harnes, D.K.; Thune, P.

    1993-01-01

    Photochemotherapy with psoralens + ultraviolet (UV)-A light (PUVA) has been used for about 16 years to treat psoriasis. Some reports have indicated a higher frequency of cutaneous squamous cell carcinoma among treated patients. The results are not consistent, however, and are not generally conceded. The material from Ullevaal Hospital comprises 585 patients who have been treated with PUVA from 1977 to 1991. Three patients developed cutaneous squamous cell carcinoma, but in one of them the tumour developed before start of PUVA treatment. The two others had received only very small doses. One of them had an intraepithelial cancer of the penis. In addition the authors registered various internal cancers in 25 patients. The Norwegian Cancer Registry compared the patient material with a matched control group as regards sex, age and age-specific incidence rate. There was no statistically significant difference in incidence between the patient and the control group. 15 refs., 1 tab

  2. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

    International Nuclear Information System (INIS)

    Kitkumthorn, Nakarin; Mutirangura, Apiwat; Yanatatsanajit, Pattamawadee; Kiatpongsan, Sorapop; Phokaew, Chureerat; Triratanachat, Surang; Trivijitsilp, Prasert; Termrungruanglert, Wichai; Tresukosol, Damrong; Niruthisard, Somchai

    2006-01-01

    The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

  3. A National-Level Validation of the New American Joint Committee on Cancer 8th Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.

    Science.gov (United States)

    Goffredo, Paolo; Garancini, Mattia; Robinson, Timothy J; Frakes, Jessica; Hoshi, Hisakazu; Hassan, Imran

    2018-06-01

    The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases. The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC. A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB (> 5 cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p  5 cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

  4. Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes

    Czech Academy of Sciences Publication Activity Database

    Strnad, Hynek; Lacina, L.; Kolář, Michal; Čada, Z.; Vlček, Čestmír; Dvořánková, B.; Betka, J.; Plzák, J.; Chovanec, M.; Šáchová, Jana; Valach, Jaroslav; Urbanová, Markéta; Smetana, K. Jr.

    2010-01-01

    Roč. 133, č. 2 (2010), s. 201-211 ISSN 0948-6143 R&D Projects: GA MŠk 2B06106 Grant - others:GA ČR(CZ) GP304/08/P175 Institutional research plan: CEZ:AV0Z50520514 Keywords : Cancer microenvironment * Epithelial–mesenchymal interaction * Cancer-associated fibroblasts Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.727, year: 2010

  5. Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men

    NARCIS (Netherlands)

    Richel, O.; Wieland, U.; de Vries, H. J. C.; Brockmeyer, N. H.; van Noesel, C.; Potthoff, A.; Prins, J. M.; Kreuter, A.

    2010-01-01

    Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV) induced potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). So far, only a few prospective studies have been performed on the topical

  6. High-Resolution Anoscopy: Clinical Features of Anal Intraepithelial Neoplasia in HIV-positive Men

    NARCIS (Netherlands)

    Richel, Olivier; Hallensleben, Nora D. L.; Kreuter, Alexander; van Noesel, Carel J. M.; Prins, Jan M.; de Vries, Henry J. C.

    2013-01-01

    BACKGROUND: High-resolution anoscopy is increasingly advocated to screen HIV+ men who have sex with men for anal cancer and its precursor lesions, anal intraepithelial neoplasia. A systematic comparison between clinical features and the histopathology of suspect lesions is lacking. OBJECTIVE: This

  7. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

    Directory of Open Access Journals (Sweden)

    Devic Ana

    2015-12-01

    Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

  8. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  9. Multiple-integrations of HPV16 genome and altered transcription of viral oncogenes and cellular genes are associated with the development of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Xulian Lu

    Full Text Available The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT. We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL and high-grade squamous intraepithelial lesions (HSIL. Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.

  10. Serum tumor marker CYFRA 21-1 in the diagnostics of squamous cell lung cancer - comparison with CEA

    International Nuclear Information System (INIS)

    Berzinec, P.; Letkovicova, M.; Arpasova, M.; Zuffova, H.

    1996-01-01

    The aim of the study was to test the diagnostic value tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were induced in this study: 56 with SQCLC - Group I, 25 with other types of lung cancer - Group II, 10 with benign respiratory tract diseases - Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - >16), in Group II: 3.58 (1.72 - >16), in Group III: 2.05 (0.99 - 3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (076- >20), in Group II: 3.32 (1.17 - >20), in Group III: 3.09 (1.84 - 6.37). There was a highly significant difference between the levels of CYFRA 21-1 in group I and Group III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.090, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this settings. (author)

  11. Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kaseb, Hatem O. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo (Egypt); Fohrer-Ting, Helene [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Lewis, Dale W. [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); Lagasse, Eric [Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219 (United States); Gollin, Susanne M., E-mail: gollin@pitt.edu [Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States); University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232 (United States)

    2016-10-15

    Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

  12. Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.

    Science.gov (United States)

    Yurugi, Yohei; Wakahara, Makoto; Matsuoka, Yuki; Sakabe, Tomohiko; Kubouchi, Yasuaki; Haruki, Tomohiro; Nosaka, Kanae; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Shiomi, Tatsushi; Nakamura, Hiroshige; Umekita, Yoshihisa

    2017-01-01

    Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

    International Nuclear Information System (INIS)

    Kaseb, Hatem O.; Fohrer-Ting, Helene; Lewis, Dale W.; Lagasse, Eric; Gollin, Susanne M.

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

  14. Stereological estimates of nuclear volume in squamous cell carcinoma of the uterine cervix and its precursors

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Bichel, P; Jakobsen, A

    1991-01-01

    -sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M...

  15. Carcinoma basalóide escamoso: uma forma rara e agressiva de câncer do esôfago e revisão da literatura Basaloid squamous carcinoma of the esophagus: a rare and aggressive form of esophageal cancer and literature review

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Coelho de Arruda Henry

    2007-03-01

    a total of 134 esophagus cancer patients in the Hospital Universitário de Botucatu-Unesp, in São Paulo, from 1990 through 1999, only one patient (0,74%, presented the basaloid squamous carcinoma of the esophagus. This patient, a 41 year-old Caucasian male farmer, presented dysfagia, regurgitation and weight loss for the last three months, being a smoker and alcoholic for many years. Endoscopy and esophagram revealed a vegetative lesion in the distal region of the esophagus. Biopsy showed a high-grade intra-epithelial neoplasm associated with basaloid cells infiltrating the corian mucosa, characteristic of the squamous basaloid carcinoma. Immunohistochemical markers were positive for carcinoembrionary antigen and high molecular weight citokeratins. Computerized tomography revealed multiple metastasis in the lungs, liver and regional lymphatic nodules, all evidence of an advanced evolution of the disease. Treatment consisted of gastrostomy. The patient presented an accentuated fall pertaining it's general state and died with a state of melena four months after diagnosis. CONCLUSION: The basaloid squamous carcinoma is a rare and aggressive form of esophagus cancer and the prognosis depends in the state at which the lesion is and in the clinical conditions of the patient at the time of diagnosis.

  16. Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells

    Directory of Open Access Journals (Sweden)

    Wang YY

    2015-02-01

    Full Text Available Yan-Yang Wang,1,2 Yin-Xue Yang,3 Ren Zhao,1 Shu-Ting Pan,2,4 Hong Zhe,1 Zhi-Xu He,5 Wei Duan,6 Xueji Zhang,7 Tianxin Yang,8 Jia-Xuan Qiu,4 Shu-Feng Zhou2,51Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 5Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, People’s Republic of China; 6School of Medicine, Deakin University, Waurn Ponds, VIC, Australia; 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 8Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USAAbstract: Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl, B-cell lymphoma 2 (Bcl-2

  17. Computational model for squamous cells characterization during cervical smear cytology

    Directory of Open Access Journals (Sweden)

    Víctor Eduardo Martínez Abaunza

    2005-07-01

    Full Text Available The main goal of the work done by the Biomedical Engineering Research Group (GIIB, and the Structural, Functional and Clinical Pathology Research Group of the Industrial University of Santander (UIS, with Autonomous University of Bucaramanga (UNAB, was to construct a computational model allowing squamous cells characterization of cervical smear cytology to classify them as being either normal or abnormal cells. Slides containing the cell samples were colleted by the pathologist and the images were digitalized by a video-camera coupled to a microscope and connected to a frame acquisition device. Three thresholding algorithms were used, in image segmentation, allowing cell nuclei detection; manual thresholding was used when these algorithms failed to detect cytoplasm. Cell texture was described by the distribution of histogram in each color level, and the borders using Fourier descriptors. The results of the first phase are presented, implementing them in classifying and identifying normal cells. Later stages will involve characterizing each cells stage initially classified as presenting some reactive change or due to infection, to distinguish the reactive cells of intraepithelial lesion cells. Key words: image processing, mathematical morphology, cervical smear cytology, dysplasia, cancer of cervix.

  18. Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Frederiksen, Maria Eiholm; Njor, Sisse; Lynge, Elsebeth

    2015-01-01

    BACKGROUND: Treatment of cervical intraepithelial neoplasia (CIN) is a common minor surgical procedure to prevent uterine cervical cancer. However, news of an abnormality detected at screening for cancer might cause the woman to worry. OBJECTIVES: To investigate the psychological consequences...... test results, but the impact decreased over time. In several but not all studies, CIN appeared to have similar psychological consequences to abnormal smears. No study showed a difference in psychological outcomes between CIN and cervical cancer diagnosis when these were measured some years after...... psychological outcomes in women with a histological diagnosis or treatment of CIN, and in women having an outcome other than CIN at cervical screening. DATA COLLECTION AND ANALYSIS: We abstracted the data using a pre-specified list of study characteristics and measured outcomes. For studies not reporting...

  19. Treatment of cervical intraepithelial neoplasia in Denmark 1991 to 2007

    DEFF Research Database (Denmark)

    Barken, Sidsel Svennekjær

    2010-01-01

    Abstract: Objectives: The number of invasive cervical cancers peaked in Denmark in 1966 with 963 cases. Cervical cancer is prevented by treatment of screen-detected cervical intraepithelial neoplasia (CIN). We assessed the trend in CIN treatments in Denmark. Material and Methods: From highly...... the data using the unique Danish identification numbers, and excluded all duplicate registrations. We excluded all destructive therapies and hysterectomies for which no CIN or cervical cancer diagnosis was found in the period from 3 months before to 1 month after the treatment date. We age......-standardized the number of cervical treatments using Danish women in 2007 as standard population. Results: The preliminary analysis shows that the number of treatments increased from about 6,000 in 1991 to about 8,200 in 2007, most noticeably due to an increase of about 2,600 in the number of conisations (Figure 1...

  20. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

    2013-05-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

  1. Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K.

    2013-01-01

    Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities

  2. Squamous cell dysplasia in the proximal rectum of three patients treated for ulcerative colitis on immunomodulators.

    Science.gov (United States)

    Connolly, James G; Goldstone, Stephen E

    2017-05-01

    Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

  3. Localized squamous-cell cancer of the esophagus: retrospective analysis of three treatment schedules

    International Nuclear Information System (INIS)

    Delcambre, Corinne; Jacob, Jacques Henry; Pottier, Didier; Gignoux, Marc; Ollivier, Jean Michel; Vie, Brigitte; Roussel, Alain; Segol, Philippe

    2001-01-01

    Background and purpose: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma. Materials and methods: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n=30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n=46), RCT group (treatment by radiochemotherapy; n=63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made. Results: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT+E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT+E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT+E group versus 75% in the RCT group, P=0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P=0.001). Conclusions: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however

  4. Rising population of survivors of oral squamous cell cancer in the United States.

    Science.gov (United States)

    Patel, Mira A; Blackford, Amanda L; Rettig, Eleni M; Richmon, Jeremy D; Eisele, David W; Fakhry, Carole

    2016-05-01

    The incidence of oropharyngeal cancer (OPC) and a subset of oral cavity cancer (OCC) is increasing in the United States. To the authors' knowledge, the presumed growing prevalence of survivors of OPC and OCC has not been investigated to date. Retrospective analysis of Surveillance, Epidemiology, and End Results data (1975-2012) estimated changes in incidence, 5-year cause-specific survival, and prevalence for OPC and OCC. Changes in incidence, cause-specific survival and prevalence were estimated by linear regression and expressed as the percentage change (B). Differences in incidence trends over time were determined by joinpoint analysis. The incidence of OPC increased by 62.6% from 1975 through 2012. Notable increases in OPC incidence were observed among men, white individuals, and those of younger ages. The 5-year survival for OPC increased significantly for all sexes, races, and individuals aged >30 years, with white individuals and males experiencing the largest increase in survival. By contrast, the incidence of OCC declined by 22.3% during the same time period. OCC incidence decreased across all groups but increased among individuals aged 30 to 39 years. Significant increases in survival were observed for OCC, except for those who were female, black, and aged American Cancer Society. © 2016 American Cancer Society.

  5. Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.

    Directory of Open Access Journals (Sweden)

    Julia Kravchenko

    Full Text Available BACKGROUND: Adenocarcinomas (ACs and squamous cell carcinomas (SCCs differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003 were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC. When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri, the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes. Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype

  6. Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Lyerly, H Kim

    2012-01-01

    Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site.

  7. nab-Paclitaxel/carboplatin in elderly patients with advanced squamous non-small cell lung cancer: a retrospective analysis of a Phase III trial

    Directory of Open Access Journals (Sweden)

    Gridelli C

    2018-05-01

    Full Text Available Cesare Gridelli,1 Tianlei Chen,2 Amy Ko,2 Mary E O’Brien,3 Teng Jin Ong,4 Mark A Socinski,5 Pieter E Postmus6 1Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy; 2Biostatistics, Celgene Corporation, Summit, NJ, USA; 3Medical Oncology, Royal Marsden Hospital, London, UK; 4Medical Affairs, Celgene Corporation, Summit, NJ, USA; 5Lung Cancer & Esophageal Cancer, Florida Hospital Cancer Institute, Orlando, FL, USA; 6Pulmonary Diseases, Clatterbridge Cancer Center, Liverpool, UK Background: Limited data on elderly patients with squamous advanced non-small cell lung cancer (NSCLC preclude optimal treatment. Here, we report the outcomes of a retrospective analysis of a subset of patients ≥70 years with squamous histology from the Phase III trial that evaluated nab-paclitaxel/carboplatin vs paclitaxel/carboplatin. Patients and methods: Patients with stage IIIB/IV NSCLC received (1:1 nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 or paclitaxel 200 mg/m2 on day 1, both with carboplatin area under the curve 6 mg×min/mL on day 1 every 3 weeks. The primary endpoint was independently assessed overall response rate as per the Response Evaluation Criteria in Solid Tumors v1.0. Secondary endpoints included progression-free survival, overall survival, and safety. Results: Sixty-five patients ≥70 years with squamous histology were included (nab-paclitaxel/carboplatin, n=35; paclitaxel/carboplatin, n=30. nab-Paclitaxel/carboplatin vs paclitaxel/carboplatin, respectively, resulted in an overall response rate of 46% vs 20% (response rate ratio, 2.29, P=0.029 and a median overall survival of 16.9 vs 8.6 months (hazard ratio, 0.50, P=0.018. No difference was observed in median progression-free survival (5.7 months for both. Incidences of grade 3/4 neutropenia (50% vs 63%, leukopenia (29% vs 37%, fatigue (3% vs 13%, and peripheral neuropathy (3% vs 13% were lower, but those of thrombocytopenia (21% vs 10% and anemia (21% vs 7% were higher with

  8. Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Therese Featherston

    2016-09-01

    Full Text Available Aim We have recently identified and characterized cancer stem cell (CSC subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC. We hypothesized that these CSCs express components of the renin-angiotensin system (RAS.Methods 3,3-Diaminobenzidine (DAB immunohistochemical (IHC staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (ATIIR2. NanoString mRNA gene expression analysis and Western Blotting (WB were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC.Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

  9. Lobular intraepithelial neoplasia arising within breast fibroadenoma

    Science.gov (United States)

    2013-01-01

    Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating

  10. Severe complications of 5-fluorouracil and cisplatin with concomitant radiotherapy in inoperable non-metastatic squamous cell oesophageal cancer after intubation - early termination of a prospective randomised trial

    Energy Technology Data Exchange (ETDEWEB)

    Alberts, A.S.; Friediger, D.; Nel, J. (Pretoria Univ. (South Africa). Dept. of Radiotherapy); Burger, W.; Schoeman, L.; Falkson, G. (Pretoria Univ. (South Africa). Dept. of Medical Oncology); Greeff, F.; Steyn, E.; Schmid, E.U. (Pretoria Univ. (South Africa). Dept. of Surgery)

    This brief letter describes a randomized trial in which radiotherapy is added to concomitant 5- fluorouracil and cisplatin therapy in patients with inoperable non-mestastatic squamous cell oesophageal cancer after palliative intubation. An interim analysis showed that patients randomized to observation had a median survival of 19 weeks while patients treated with radiotherapy, 5- fluorouracil and cisplatin had a median survival of 11 weeks. This difference in survival was due to the toxicity of the combined chemoradiotherapy and tube which resulted in early termination of the trial. (UK).

  11. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence

    DEFF Research Database (Denmark)

    Kjær, Susanne K; Frederiksen, Kirsten; Plum, Christian Edinger Munk

    2010-01-01

    Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection...

  12. Oral cancer

    Science.gov (United States)

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... National Cancer Institute. PDQ lip and oral cavity cancer ... September 25, 2015. www.cancer.gov/types/head-and-neck/hp/lip- ...

  13. Photochemotherapy - psoralens + UV-A(PUVA) - does it increase the risk for cancer. Fotokjemoterapi - psoralen + UV-A(PUVA) - oeket risiko for kreft

    Energy Technology Data Exchange (ETDEWEB)

    Harnes, D K; Thune, P [Ullevaal Hospital, Oslo (Norway)

    1993-01-01

    Photochemotherapy with psoralens + ultraviolet (UV)-A light (PUVA) has been used for about 16 years to treat psoriasis. Some reports have indicated a higher frequency of cutaneous squamous cell carcinoma among treated patients. The results are not consistent, however, and are not generally conceded. The material from Ullevaal Hospital comprises 585 patients who have been treated with PUVA from 1977 to 1991. Three patients developed cutaneous squamous cell carcinoma, but in one of them the tumour developed before start of PUVA treatment. The two others had received only very small doses. One of them had an intraepithelial cancer of the penis. In addition the authors registered various internal cancers in 25 patients. The Norwegian Cancer Registry compared the patient material with a matched control group as regards sex, age and age-specific incidence rate. There was no statistically significant difference in incidence between the patient and the control group. 15 refs., 1 tab.

  14. Large scale study of HPV genotypes in cervical cancer and different cytological cervical specimens in Thailand.

    Science.gov (United States)

    Chansaenroj, Jira; Junyangdikul, Pairoj; Chinchai, Teeraporn; Swangvaree, Sukumarn; Karalak, Anant; Gemma, Nobuhiro; Poovorawan, Yong

    2014-04-01

    Identification of high-risk HPV genotypes in patients is essential for vaccination and prevention programs while the geographic distribution of cervical cancer varies widely. HPV 16 is the major cause of cervical cancer followed by HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study, the distribution of HPV genotypes in cervical specimens from women living in Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct sequencing. The 716 specimens were grouped according to their cytological grades; 100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade squamous intraepithelial lesions, and 416 specimens of cervical cancer. The results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV genotypes in Thailand, respectively. With respect to age, women below the age of 26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high prevalence of high-risk HPV DNA and abnormal cytology were usually found in women between 26 and 45 years while cervical cancer was detected mainly in women above the age of 45 years. To increase protection efficiency, a vaccine including HPV 52 and HPV 58 should be offered to Asian women, and primary HPV screening should start at 26-30 years of age. © 2013 Wiley Periodicals, Inc.

  15. Human Papillomavirus types distribution among women with cervical preneoplastic, lesions and cancer in Luanda, Angola.

    Science.gov (United States)

    Damião, Paciência de Almeida; Oliveira-Silva, Michelle; Moreira, Miguel Ângelo; Poliakova, Natalia; de Lima, Maria Emilia Rt; Chiovo, José; Nicol, Alcina Frederica

    2016-01-01

    Cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. To determine the frequency of HPV among women with squamous intraepithelial lesions from women in Luanda, Angola. Study participants included women diagnosed with cytological abnormalities that voluntarily provided Pap smears (n = 64). Genomic DNA was extracted from the samples for use as templates in the PCR amplification of HPV sequences. PCR products were sequenced to determine HPV type. HPV DNA was detected in 71.9% (46/64) in the samples. A higher diversity of HPV types was found in the cytological lesions, such as ASCUS and LSIL (HPV16, 6, 18, 31, 58, 66, 70 and 82, in order of frequency) than that detected for HSIL and SSC (HPV16, 18, 6 and 33). The most prevalent HPV type were: HPV16, HPV6 and HPV18. This is the first report on HPV type diversity and frequency in woman of Angola. The results suggest that large-scale studies across Africa would improve our understanding of interrelationship between HPV infections and cervical cancer. More directly, the identification of the HPV types most prevalent suggests that women in Angola would benefit from currently available HPV vaccines.

  16. Prevalence status and association with human papilloma virus of anal squamous proliferative lesions in a patient sample in Taiwan.

    Science.gov (United States)

    Tsai, Tsen-Fang; Kuo, Guan-Tin; Kuo, Lu-Ting; Hsiao, Cheng-Hsiang

    2008-08-01

    Anal squamous proliferative lesions, including condyloma, anal high-grade squamous intraepithelial lesion (AHSIL) and squamous cell carcinoma (SCC), are associated with human papilloma virus (HPV) infection. The objectives of the study were to investigate the HPV prevalence of anal squamous proliferative lesion in Taiwan. From 1991 to 2005, 41 cases with condyloma, 12 cases with AHSIL, and 13 cases with SCC were collected. DNA was extracted from the tissue sections of these patients, and the HPV genotype was identified using polymerase chain reaction and gene chip. The integration status of HPV16 DNA was also evaluated by quantitative real-time polymerase chain reaction. Anal condyloma mainly occurred in young males, but AHSIL and anal SCC developed in older patients. In the patients with human immunodeficiency virus (HIV) infection, AHSIL developed much earlier than patients without HIV infection (36 vs. 61 years). HPV DNA was detected in all 56 patients whose specimens contained adequate DNA. High-risk HPVs (type 16, 58, etc.) were mainly detected in the AHSIL and SCC. Multiple HPV infection was found in AHSIL (4 of 12) and condyloma (11 of 34) but was rare in invasive cancer (1 of 12). Seven of 8 patients with HPV16 infection had coexistent episomal and integrated forms. HPV58 is a unique high-risk HPV prevalent in Taiwan. The integration status of HPV seems not correlated with the severity of the dysplasia. In our study, emerging HIV-positive AHSIL in recent years indicates that we should devote more efforts to promote sexual safety among the people who engaged in anal intercourse.

  17. The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

    2009-01-01

    Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

  18. Safety and Efficacy of Concurrent Cisplatin and Radiotherapy in Inoperable or Metastatic Squamous Cell Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Shaleen; Dimri, Kislay; Datta, Niloy R.; Rastogi, Neeraj; Lal, Punita; Das, Koilpillai J. Maria; Ayyagari, Sundar [Sanjay Gandhi Postgraduate Inst. of Medical Sciences, Lucknow (India). Dept of Radiotherapy

    2002-09-01

    Between August 1996 and May 1999, 50 consecutive, previously untreated patients with carcinoma of the esophagus and who were inoperable for various reasons were treated with weekly doses of cisplatin (35 mg/m{sup 2}, maximum 7 cycles) concurrent with either 66 Gy/33 fractions external beam radiotherapy (EBRT) (n=42) or 50 Gy/25 fractions EBRT and two insertions of high-dose-rate intraluminal radiotherapy of 6 Gy each, spaced a week apart (n=8). Eighty-two percent (41/50) of the patients received the stipulated radiotherapy (RT) dose. Seventy-six percent (38/50) received at least 6 cycles of chemotherapy. Neutropenia in the form of WHO grade II-12% (6/50) and grade III-2% (1/50) was observed. Grade III emesis was seen in 8% (4/50). Improvement in the swallowing status was seen in 84% (42/50). Median duration of dysphagia relief was 6 months. The median overall survival was 9 months with 17% estimated to be alive after 4 years. Combined treatment with single agent cisplatin and definitive radiotherapy for inoperable cancer of the esophagus is safe, well tolerated and reasonably efficacious.

  19. Safety and Efficacy of Concurrent Cisplatin and Radiotherapy in Inoperable or Metastatic Squamous Cell Esophageal Cancer

    International Nuclear Information System (INIS)

    Kumar, Shaleen; Dimri, Kislay; Datta, Niloy R.; Rastogi, Neeraj; Lal, Punita; Das, Koilpillai J. Maria; Ayyagari, Sundar

    2002-01-01

    Between August 1996 and May 1999, 50 consecutive, previously untreated patients with carcinoma of the esophagus and who were inoperable for various reasons were treated with weekly doses of cisplatin (35 mg/m 2 , maximum 7 cycles) concurrent with either 66 Gy/33 fractions external beam radiotherapy (EBRT) (n=42) or 50 Gy/25 fractions EBRT and two insertions of high-dose-rate intraluminal radiotherapy of 6 Gy each, spaced a week apart (n=8). Eighty-two percent (41/50) of the patients received the stipulated radiotherapy (RT) dose. Seventy-six percent (38/50) received at least 6 cycles of chemotherapy. Neutropenia in the form of WHO grade II-12% (6/50) and grade III-2% (1/50) was observed. Grade III emesis was seen in 8% (4/50). Improvement in the swallowing status was seen in 84% (42/50). Median duration of dysphagia relief was 6 months. The median overall survival was 9 months with 17% estimated to be alive after 4 years. Combined treatment with single agent cisplatin and definitive radiotherapy for inoperable cancer of the esophagus is safe, well tolerated and reasonably efficacious

  20. Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer

    Science.gov (United States)

    2018-05-31

    ATM Gene Mutation; ATR Gene Mutation; BARD1 Gene Mutation; BRCA1 Gene Mutation; BRCA2 Gene Mutation; BRIP1 Gene Mutation; CHEK1 Gene Mutation; CHEK2 Gene Mutation; FANCA Gene Mutation; FANCC Gene Mutation; FANCD2 Gene Mutation; FANCF Gene Mutation; FANCM Gene Mutation; NBN Gene Mutation; PALB2 Gene Mutation; RAD51 Gene Mutation; RAD51B Gene Mutation; RAD54L Gene Mutation; Recurrent Squamous Cell Lung Carcinoma; RPA1 Gene Mutation; Stage IV Squamous Cell Lung Carcinoma AJCC v7

  1. Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia

    International Nuclear Information System (INIS)

    Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C.

    2010-01-01

    The authors report the results of an exclusive low dose rate curie therapy for female patients treated for a grade 3 vaginal intraepithelial neoplasia. They reviewed the medical files of patients treated since 1983, i.e. 28 women. They analysed demographic characteristics, the clinic description of lesions, possible treatments which occurred before this high-grade vaginal intraepithelial neoplasia, possible previous history of cervical or endometrial cancer, curie therapy detailed data, presence of tumorous relapse. According to that, they conclude that a 60 Gy exclusive low- vaginal dose-rate curie-therapy is an efficient and well tolerated treatment for high-grade vaginal intraepithelial neoplasia. Short communication

  2. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-01-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

  3. High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Erpolat, O.P.; Akmansu, M. [Medical School of Gazi Univ., Besevler-Ankara (Turkey). Dept. of Radiation Oncology; Gocun, P.U.; Karakus, E.; Akyol, G. [Medical School of Gazi Univ., Besevler-Ankara (Turkey). Dept. of Pathology

    2012-03-15

    Survivin is one of the apoptosis inhibitor proteins. Together with Aurora B, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion.

  4. Prognostic Relevance of HPV Infection and p16 Overexpression in Squamous Cell Anal Cancer

    International Nuclear Information System (INIS)

    Mai, Sabine; Welzel, Grit; Ottstadt, Martine; Lohr, Frank; Severa, Sebastin; Prigge, Elena-Sophie; Wentzensen, Nicolas; Trunk, Marcus J.; Wenz, Frederik; Knebel-Doeberitz, Magnus von; Reuschenbach, Miriam

    2015-01-01

    Purpose: Human papillomavirus (HPV) DNA and p16 status have both been reported as prognostic factors in anal cancer, but the prognostic relevance of combined detection and particularly HPV−/p16+ and HPV+/p16− signatures is unknown. We evaluated combined HPV DNA and p16 status as a prognostic factor of treatment response in anal cancer. Methods: 106 patients treated with radiochemotherapy (RCT+5-FU/MMC) with available paraffin-embedded tumor tissue specimens were evaluated regarding local control (LC) and overall survival (OS) at 5 years. In addition to HPV DNA/p16 status, the influence of age, gender, previous surgery, initial recurrence, T stage, N status, and tumor localization was analyzed. Results: 63 patients were HPV+/p16+, 9 were HPV+/p16−, 11 were HPV−/p16+, and 23 were HPV−/p16−. In univariate analysis, LC was significantly better in patients with T1/2 stage, female gender, and HPV/p16 status. HPV+/p16+ was associated with significantly better LC (88.1%; 95% confidence interval [CI]: 78.89-97.31) compared with HPV−/p16+ (63.6%; 95% CI: 35.18-92.02; P=.021) and especially HPV−/p16− (55.8%; 95% CI: 33.46-78.14; P=.002) but not with HPV+/p16− (77.8%; 95% CI: 50.56-105.04; P=.270). OS was influenced by T stage and LC. HPV+/p16+ patients showed a trend toward better OS compared with HPV−/p16− patients (HPV+/p16+: 81.1%; 95% CI: 70.12-92.08 vs HPV−/p16−: 68.8%; 95%CI: 47.44-90.16; P=.138). On multivariate analysis, T3/4 stage and HPV/p16 status (HPV−/p16+, HPV−/p16− vs HPV+/p16+) predicted poorer LC (T3/4: 50.3% vs T1/2: 86.6%, hazard ratio [HR] 0.22; 95% CI: 0.09-0.53; P<.001; HPV+/p16+ vs HPV−/p16+: HR 4.73; 95% CI: 1.33-16.82; P=.016, and HPV+/p16+ vs HPV−/p16−: HR 6.40; 95% CI: 2.23-18.35; P<.001), whereas local relapse dramatically influenced OS. Conclusion: Our data suggest that HPV/p16 signature determines prognosis. HPV+/p16+ patients had the best prognosis, and HPV−/p16+ and HPV−/p16− patients

  5. Prognostic Relevance of HPV Infection and p16 Overexpression in Squamous Cell Anal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Sabine, E-mail: sabine.mai@umm.de [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Welzel, Grit; Ottstadt, Martine; Lohr, Frank; Severa, Sebastin [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Prigge, Elena-Sophie [Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg (Germany); Wentzensen, Nicolas [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (United States); Trunk, Marcus J. [Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Wenz, Frederik [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Knebel-Doeberitz, Magnus von; Reuschenbach, Miriam [Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg (Germany)

    2015-11-15

    Purpose: Human papillomavirus (HPV) DNA and p16 status have both been reported as prognostic factors in anal cancer, but the prognostic relevance of combined detection and particularly HPV−/p16+ and HPV+/p16− signatures is unknown. We evaluated combined HPV DNA and p16 status as a prognostic factor of treatment response in anal cancer. Methods: 106 patients treated with radiochemotherapy (RCT+5-FU/MMC) with available paraffin-embedded tumor tissue specimens were evaluated regarding local control (LC) and overall survival (OS) at 5 years. In addition to HPV DNA/p16 status, the influence of age, gender, previous surgery, initial recurrence, T stage, N status, and tumor localization was analyzed. Results: 63 patients were HPV+/p16+, 9 were HPV+/p16−, 11 were HPV−/p16+, and 23 were HPV−/p16−. In univariate analysis, LC was significantly better in patients with T1/2 stage, female gender, and HPV/p16 status. HPV+/p16+ was associated with significantly better LC (88.1%; 95% confidence interval [CI]: 78.89-97.31) compared with HPV−/p16+ (63.6%; 95% CI: 35.18-92.02; P=.021) and especially HPV−/p16− (55.8%; 95% CI: 33.46-78.14; P=.002) but not with HPV+/p16− (77.8%; 95% CI: 50.56-105.04; P=.270). OS was influenced by T stage and LC. HPV+/p16+ patients showed a trend toward better OS compared with HPV−/p16− patients (HPV+/p16+: 81.1%; 95% CI: 70.12-92.08 vs HPV−/p16−: 68.8%; 95%CI: 47.44-90.16; P=.138). On multivariate analysis, T3/4 stage and HPV/p16 status (HPV−/p16+, HPV−/p16− vs HPV+/p16+) predicted poorer LC (T3/4: 50.3% vs T1/2: 86.6%, hazard ratio [HR] 0.22; 95% CI: 0.09-0.53; P<.001; HPV+/p16+ vs HPV−/p16+: HR 4.73; 95% CI: 1.33-16.82; P=.016, and HPV+/p16+ vs HPV−/p16−: HR 6.40; 95% CI: 2.23-18.35; P<.001), whereas local relapse dramatically influenced OS. Conclusion: Our data suggest that HPV/p16 signature determines prognosis. HPV+/p16+ patients had the best prognosis, and HPV−/p16+ and HPV−/p16− patients

  6. Squamous Cell Carcinoma Antigen in Follow-Up of Cervical Cancer Treated With Radiotherapy: Evaluation of Cost-Effectiveness

    International Nuclear Information System (INIS)

    Forni, Franca; Ferrandina, Gabriella; Deodato, Francesco; Macchia, Gabriella; Morganti, Alessio G.; Smaniotto, Daniela; Luzi, Stefano; D'Agostino, Giuseppe; Valentini, Vincenzo; Cellini, Numa; Giardina, Bruno; Scambia, Giovanni

    2007-01-01

    Purpose: The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. Methods and Materials: The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. Results: A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. Conclusions: Our results have shown that a simplified diagnostic approach, including

  7. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  8. Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

    Science.gov (United States)

    Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O

    The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial

    DEFF Research Database (Denmark)

    Alkureishi, Lee W T; Ross, Gary L; Shoaib, Taimur

    2010-01-01

    Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes...

  10. Immunohistochemical study of p16 INK4A and survivin expressions in cervical squamous neoplasm

    Directory of Open Access Journals (Sweden)

    Tan Geok

    2010-01-01

    Full Text Available Introduction:Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm. Material and Methods: This is a retrospective study on 201 cases of cervical neoplasm comprising of 129 cervical intraepithelial neoplasia (CIN and 72 squamous cell carcinoma (SCC. All samples were evaluated by two independent observers using p16INK4A and survivin monoclonal antibodies. The p16 INK4A expression was graded as negative, focal and diffuse positivity. The intensity for survivin expression was graded as weak, moderate and intense. Results: It is seen that p16 INK4A expression in CIN 1, CIN 2 and CIN 3 were 25.4%, 42.9% and 95.9% respectively. Majority of SCC (98.6% showed p16 INK4A expression. Survivin expressions in CIN 1, CIN 2, CIN 3 and SCC were 56.7%, 33.4%, 87.5% and 98.6%. There was a linear relationship between increasing grade of CIN and p16 INK4A expressions. Conclusion: Our study showed that p16 INK4A expressions correlate well with the increasing grade of CIN. Although survivin does not correlate well to the increasing grade of CIN, it could be useful in differentiating CIN 3 from SCC.

  11. Radionuclides detected in lime samples that consumed with tobacco and betel nuts by people of Northeast India where head and neck squamous cells cancer (HNSCC) is prevalent

    International Nuclear Information System (INIS)

    Dilip Bhattacharjee; Satoru Endo; Kenichi Tanaka; Masaharu Hoshi

    2007-01-01

    Complete text of publication follows. Head and neck squamous cell cancer (HNSCC) is a very predominant type of cancer amongst the population of northeastern states of India than the rest of the world. Epidemiological and other data suggest consumption of betel nuts with/without tobacco and lime or tobacco alone with lime is a probable cause of high cancer incidence. The fundamental question arises that why this particular cancer is induced more in this region while people follow the similar habits elsewhere. Here we report the results on analysis of lime samples, collected from 12 different locations spectrophotometrically by high-purity germanium detector. The calculated activity of radionuclides showed to an average of 2.68, 0.10 and 0.83 Bq/gm for 238 U, 235 U and 232 Th series respectively for ten samples which are about 8 times higher than the normal background level of 0.37, 0.02 and 0.02 Bq/gm for 238 U, 235 U and 232 Th series found in control samples, collected from outside of northeast. The results conclusively showed for the first time that the lime samples almost throughout the northeastern India contain high proportion of radionuclides of uranium, thorium and actinides series. Further, annual effective dose of gamma radiation calculations from these results of earth's crust in northeast showed that gamma rays emitted at an average dose of up to 2.5 mSv/year/consumer approximately. This dose calculation in the oral cavity is underestimated as short range radiations by decay of alpha, beta and electron-capture etc are not considered in the present study. Continuous exposure of such low dose radiations emitting from different radionuclides to the sensitive squamous cells of the oral cavity for a long twenty years or more amounting to a total minimum dose of at least 50 mSv evidently contributes towards excessive HNSCC to the people of northeast than other parts of India.

  12. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  13. Impact of DNA demethylation of the G0S2 gene on the transcription of G0S2 in squamous lung cancer cell lines with or without nuclear receptor agonists

    International Nuclear Information System (INIS)

    Kusakabe, Masashi; Watanabe, Kousuke; Emoto, Noriko; Aki, Naomi; Kage, Hidenori; Nagase, Takahide; Nakajima, Jun; Yatomi, Yutaka; Ohishi, Nobuya; Takai, Daiya

    2009-01-01

    We recently identified that DNA methylation of the G0S2 gene was significantly more frequent in squamous lung cancer than in non-squamous lung cancer. However, the significance of G0S2 methylation levels on cancer cells is not yet known. We investigated the effect of G0S2 methylation levels on cell growth, mRNA expression, and chromatin structure using squamous lung cancer cell lines and normal human bronchial epithelial cells. DNA methylation and mRNA expression of G0S2 were inversely correlated, and in one of the squamous lung cancer cell lines, LC-1 sq, G0S2 was completely methylated and suppressed. Overexpression of G0S2 in LC-1 sq did not show growth arrest or apoptosis. The G0S2 gene has been reported to be a target gene of all-trans retinoic acid and peroxisome proliferator-activated receptor agonists. We treated LC-1 sq with 5-Aza-2'-deoxycytidine, Trichostatin A, all-trans retinoic acid, Wy 14643, or Pioglitazone either alone or in combination. Only 5-Aza-2'-deoxycytidine restored mRNA expression of G0S2. Chromatin immunoprecipitation revealed that histone H3 lysine 9 was methylated regardless of DNA methylation or mRNA expression. In summary, mRNA expression of G0S2 was regulated mainly by DNA methylation in squamous lung cancer cell lines. When the G0S2 gene was methylated, nuclear receptor agonists could not restore mRNA expression of G0S2 and did not show any additive effect on mRNA expression of G0S2 even after the treatment with 5-Aza-2'-deoxycytidine.

  14. Visual inspection with acetic acid (via screening program: 7 years experience in early detection of cervical cancer and pre-cancers in rural South India

    Directory of Open Access Journals (Sweden)

    Usha Rani Poli

    2015-01-01

    Full Text Available Cervical cancer continues to be a major public health problem in India in the absence of wide spread organised cervical screening programs. Visual inspection of the cervix with acetic acid (VIA is an effective, inexpensive screening test that can be combined with simple treatment procedures for early cervical lesions, provided by trained health workers. We report 7 years experience in early detection of cervical cancer and pre-cancers using the VIA test in a community-based program in rural Andhra Pradesh, India where there are no existing organised cervical screening programs. Materials and Methods: Eligible women aged between 26 and 60 were opportunistically screened by trained health wor kers using the VIA test. Women who tested positive were further evaluated and those with cervical lesions were treated either by cryotherapy in the screening clinic or referred to a higher center. Results: A total of 18,869 women were screened by a single round of VIA testing with a positive rate of 10.75%. Biopsy proven high-grade squamous intraepithelials (HSILs were 90 (0.48% and low-grade squamous intraepithelials (LSILs were 43 (0.28%. The overall prevalence of cervical intraepithelial neoplasia (CIN 2+ lesion rate is 1.05%. A total of 312 (1.65% cryotherapies were done and 49 women underwent hysterectomy. Conclusions: VIA by trained female health workers is a safe, acceptable, and effective test that can save lives from cervical cancer even in remote areas with few resources. These results have important implications for efficient service delivery in cervical screening programs in low-resourced settings.

  15. Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer : treating the right patients based on individualized treatment effect prediction

    NARCIS (Netherlands)

    van Kruijsdijk, R. C. M.; Visseren, F. L. J.; Boni, L.; Groen, H. J. M.; Dingemans, A. M. C.; Aerts, J. G. J. V.; van der Graaf, Y.; Ardizzoni, A.; Smit, E. F.

    In this study, it is shown that there is important heterogeneity in the effects of pemetrexed-carboplatin versus pemetrexed on progression-free survival in pretreated patients with advanced non-squamous non-small-cell lung cancer. Treatment effect can be predicted for individual patients using a

  16. Pretreatment red blood cell total folate is associated with response to pemetrexed in stage IV non-squamous non-small-cell lung cancer

    Science.gov (United States)

    Bagley, Stephen J.; Vitale, Steven; Zhang, Suhong; Aggarwal, Charu; Evans, Tracey L.; Alley, Evan W.; Cohen, Roger B.; Langer, Corey J.; Blair, Ian A.; Vachani, Anil; Whitehead, Alexander S.

    2016-01-01

    Objectives Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Prior studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic marker of cellular folate status, was associated with response to pemetrexed-based chemotherapy in advanced non-squamous non-small-cell lung cancer (NSCLC). Materials and methods We conducted a prospective cohort study of patients with stage IV non-squamous NSCLC receiving first-line chemotherapy containing pemetrexed. Pretreatment RBC total folate was quantified using liquid chromatography/mass spectrometry. We then compared objective response rate (ORR) between patients with RBC total folate concentrations above and below an optimal cut-off value determined from the receiver operating characteristic (ROC) curve. A logistic regression model was used to adjust for age, sex, and use of bevacizumab. Results The ORR was 62% (32 of 52 patients). ROC analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and non-responders. Patients with RBC total folate below 364.5 nM had an ORR of 27%, compared to 71% in patients with RBC total folate above this value (p=0.01). This difference persisted after adjusting for age, sex, and use of bevacizumab (OR 0.07, 95% CI 0.01 - 0.57, p=0.01). Conclusions Low pretreatment RBC total folate is associated with inferior response to pemetrexed-based chemotherapy in stage IV non-squamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response. PMID:27863923

  17. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

    Science.gov (United States)

    Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

    2017-12-01

    There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Prevalence and clinical significance of cancer cachexia based on time from treatment in advanced-stage head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kwon, Minsu; Kim, Rock Bum; Roh, Jong-Lyel; Lee, Sang-Wook; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2017-04-01

    The purpose of this study was to identify the prevalence of cancer cachexia and its prognostic impact in patients with advanced head and neck squamous cell carcinoma (HNSCC). The prevalence of cancer cachexia was analyzed according to the follow-up periods during the first year after curative initial treatment. Recurrences, noncancer health events (NCHEs), and cause-specific survival outcomes were also analyzed according to the incidence of cancer cachexia during follow-up. Cancer cachexia was identified in 22 (6.1%), 148 (41%), 66 (18.4%), and 65 (18.7%) of 361 enrolled patients at pretreatment, immediately after treatment, 6-months after treatment, and 12-months after treatment, respectively. Sustained or newly developed cachexia at 6 and 12 months showed a significant association with recurrence and NCHE occurrence (p cachexia had a higher probability of cancer-specific death, noncancerous death, and overall death (p Cachexia prevalence at 6 and 12 months after treatment for HNSCC indicates a higher chance of recurrence, NCHE, and death. © 2016 Wiley Periodicals, Inc. Head Neck 39: 716-723, 2017. © 2016 Wiley Periodicals, Inc.

  19. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  20. Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

    2008-05-01

    To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

  1. Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

    Science.gov (United States)

    Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

    2018-01-01

    Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

  2. Changes in cross-sectional area of pulmonary vessels on chest computed tomography after chemotherapy in patients with advanced non-squamous non-small-cell lung cancer.

    Science.gov (United States)

    Karayama, Masato; Inui, Naoki; Kusagaya, Hideki; Suzuki, Seiichiro; Inoue, Yusuke; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Suda, Takafumi

    2016-05-01

    Chemotherapy is associated with a risk of vascular damage. Novel anti-angiogenic agents, which can directly affect tumor angiogenesis, are increasingly being used. However, the effects of these agents on normal vasculature are not well understood. Here, we evaluated the effects of chemotherapy in general, and the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary vasculature in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA), which is an easily measurable indicator of small pulmonary vasculature on non-contrast chest computed tomography (CT). We retrospectively reviewed CT scans of the lungs of 75 chemo-naïve patients with advanced non-squamous NSCLC, for measurement of CSA, before and after first-line platinum-based chemotherapy, using a semi-automatic image-processing program. Measured vessels were classified in two groups: small vessels with CSA area (%CSAsmall-diameter vessels, with a significant decrease in %CSAsmall pulmonary vascular damage. Use of bevacizumab does not enhance the reduction in area of pulmonary vessels.

  3. Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    He, Xiaoyan; Zhang, Zhimei; Li, Ming; Li, Shuo; Ren, Lihua; Zhu, Hong; Xiao, Bin; Shi, Ruihua

    2015-01-01

    Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3′ untranslated region (3′-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2. The online version of this article (doi:10.1186/s12885-015-1581-6) contains supplementary material, which is available to authorized users

  4. The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Fujiwara, Daisuke; Kato, Kazunori; Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki

    2013-01-01

    was enhanced, suggesting that hypoxia had been induced. Comparison of cancer drug resistance using cisplatin and doxorubicin in 3-D-cultured esophageal cancer cells showed that cancer drug resistance had increased. These results indicate that 3-D culture of esophageal squamous cell carcinoma lines is a useful method for inducing cancer stem cells

  5. Characterization of a group of patients with cervical intraepithelial neoplasia diagnosed by diathermic loop biopsy

    International Nuclear Information System (INIS)

    Torriente Hernandez, Santa; Valdes Alvarez, Orlando; Villarreal Martinez, Aracelis; Lugo Sanchez, Ana

    2011-01-01

    A retrospective, longitudinal and descriptive study was conducted in 2 696 medical records corresponding to patients diagnosed with cervical intraepithelial neoplasia (CIN) and invasive cancer of cervix uteri (CCU) seen in the mother hospital of Guanabacoa municipality over above mentioned period. The information processing was from the data retrieval from medical records and biopsy control registry entering in a database in Microsoft Excel and the statistic processing using the SPSS package version 15 and EPIDAT

  6. Berberine enhances radiosensitivity of esophageal squamous cancer by targeting HIF-1α in vitro and in vivo

    OpenAIRE

    Yang, Xi; Yang, Baixia; Cai, Jing; Zhang, Chi; Zhang, Qu; Xu, Liping; Qin, Qin; Zhu, Hongcheng; Ma, Jianxin; Tao, Guangzhou; Cheng, Hongyan; Sun, Xinchen

    2013-01-01

    Radiation therapy is an important treatment approach for esophageal squamous cell carcinoma (ESCC). However, how to promote radiation sensitivity in ESCC remains a challenge. This study aimed to evaluate the effects of berberine, a common used Chinese medicine, on the radiosensitivity of ESCC. ECSS cell line ECA109 and TE13 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and survival, and apoptosis were evaluated. In add...

  7. The value of perfusion CT in predicting the short-term response to synchronous radiochemotherapy for cervical squamous cancer

    International Nuclear Information System (INIS)

    Li, Xiang Sheng; Fan, Hong Xia; Zhu, Hong Xian; Song, Yun Long; Zhou, Chun Wu

    2012-01-01

    To determine the value of the perfusion parameters in predicting short-term tumour response to synchronous radiochemotherapy for cervical squamous carcinoma. Ninety-three patients with cervical squamous carcinoma later than stage IIB were included in this study. Perfusion CT was performed for all these patients who subsequently received the same synchronous radiochemotherapy. The patients were divided into responders and non-responders according to short-term response to treatment. Baseline perfusion parameters of the two groups were compared. The perfusion parameters that might affect treatment effect were analysed by using a multivariate multi-regression analysis. The responders group had higher baseline permeability-surface area product (PS) and blood volume (BV) values than the non-responders group (P 0.05). At multivariate multi-regression analysis, BV, PS and tumour size were significant factors in the prediction of treatment effect. Small tumours usually had high PS and BV values, and thus had a good treatment response. Perfusion CT can provide some helpful information for the prediction of the short-term effect. Synchronous radiochemotherapy may be more effective in cervical squamous carcinoma with higher baseline PS and BV. (orig.)

  8. Histologic transformation from adenocarcinoma to both small cell lung cancer and squamous cell carcinoma after treatment with gefitinib: A case report.

    Science.gov (United States)

    Yao, Yufeng; Zhu, Zhouyu; Wu, Yimin; Chai, Ying

    2018-05-01

    In the past decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment had been an important therapy for treating advanced EGFR-mutated lung cancer patients. However, a large number of these patients with EGFR-TKIs treatment always acquired resistance to these drugs in one year. The histologic transformation is an important resistance mechanism. Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib. A case of EGFR-mutated lung cancer. Medical thoracoscopy examination was performed and the patient was diagnosed as a EGFR-mutated lung adenocarcinoma. Then gefitinib was administered orally at a dose of 250 mg daily. The patient received treatment with chemotherapy (etoposide 0.1 g day 2-5 +  cis-platinum 30 mg day 2-4) after acquiring resistance to gefitinib. The patient died in April 2017 that survived for 32 months from lung cancer was found for the first time. To the best of our knowledge, it is the first case of EGFR-mutated lung adenocarcinoma transforming to both SCLC and SCC which was treated with and responded to gefitinib.

  9. Definitive intensity-modulated radiotherapy concurrent with systemic therapy for oropharyngeal squamous cell carcinoma: Outcomes from an integrated regional Australian cancer centre

    International Nuclear Information System (INIS)

    Rahbari, Reza M.; McKay, Michael; Dwyer, Patrick; Winkley, Lauren; Hill, Jacques; Last, Andrew; Tahir, Abdul R.M.; Shakespeare, Thomas P.

    2016-01-01

    Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased over the past two decades largely because of an increase in human papilloma virus (HPV)-related OPSCC. We report here outcomes of definitive radiation therapy for OPSCC with simultaneous integrated boost intensity-modulated radiotherapy (IMRT) in a regional Australian cancer centre. We retrospectively reviewed electronic medical records (EMR) of all patients treated with IMRT for head and neck cancer. We included patients who received a curative intent IMRT for OPSCC (2010–2014). Of 61 patients, 80% were men, and the median age was 57 years. Ninety percent of our patients received concurrent systemic therapy, and 68% were p16 positive. The median radiotherapy dose received was 70 Gy in 35 fractions. The median follow up for surviving patients was 22 months. Twenty-four month actuarial data show that the loco-regional recurrence free, metastasis-free MFS, cancer-specific (CaSS) and overall survival percentages were 98.3%, 92.6%, 91% and 90.3%, respectively. We did not observe grades 4 or 5 acute or late toxicities, and 10 patients (16.2%) exhibited persistent grade 3 toxicity 6 months after completing the treatment. The results from curative IMRTs for OPSCC delivered in a regional cancer centre are comparable with results published by tertiary referral centres. A long-term follow up of this patient cohort will continue for further analyses and comparisons with tertiary centres.

  10. Cancer/testis antigens: A prospective reagent as diagnostic and immunotherapeutic targets for squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Shohei Domae

    2014-11-01

    Full Text Available Numerous tumor antigens have so far been identified from various tumors using the serological identification of antigens by recombinant expression cloning (SEREX method. Among them, cancer/testis (CT antigens are considered promising target molecules for immunotherapy for patients with various cancers. We performed several SEREX analyses of various cancers to identify CT antigens, including gastric adenocarcinoma, lung adenocarcinoma, and colon cancer, and consequently identified additional CT antigens, such as XAGE-1, CCDC62-2, GKAP1, and TEKT5. However, although SEREX analysis of squamous cell carcinoma of the head and neck (HNSCC has been performed several times, only a few CT or HNSCC specific antigens have yet been isolated. Compared with other tumors, a small number of studies have been reported on the antigen proteins specific to HNSCC. We here reported the expression of selected CT antigens and their immunogenicity in patients with HNSCC. The results obtained suggested that CCDC62-2, GKAP1, and TEKT5 are immunogenic in HNSCC and also demonstrated their potencies as diagnostic markers for patients with HNSCC in combination with other CT antigens such as NY-ESO-1, MAGE-A3, and MAGE-A4.

  11. New Developments in Ocular Surface Squamous Neoplasia

    Directory of Open Access Journals (Sweden)

    Ayşe Yağcı

    2014-09-01

    Full Text Available Ocular surface squamous neoplasia originates from conjunctiva epithelium and covers a broad spectrum of disease ranging from dysplasia to squamous cell carcinoma. Clinical features may vary from case to case. Traditional treatment of excision with no-touch technique combined with adjuvant therapies because of high recurrence rate. Main adjuvant treatments are cryotherapy and chemotherapy. In this review, clinical forms, differential diagnosis, American Joint Committee on Cancer classification and recent approaches to the management of ocular surface squamous dysplasia were described. (Turk J Ophthalmol 2014; 44: Supplement 8-14

  12. Benefit-Risk Summary of Nivolumab for Patients With Metastatic Squamous Cell Lung Cancer After Platinum-Based Chemotherapy: A Report From the US Food and Drug Administration.

    Science.gov (United States)

    Kazandjian, Dickran; Khozin, Sean; Blumenthal, Gideon; Zhang, Lijun; Tang, Shenghui; Libeg, Meredith; Kluetz, Paul; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2016-01-01

    Metastatic squamous non-small-cell lung cancer (SQ NSCLC) is a serious and life-threatening malignant condition with unmet medical need. In late December 2014, the US Food and Drug Administration (FDA) obtained the data monitoring committee report of a planned interim analysis of a trial in second-line SQ NSCLC (CM017) that demonstrated an overall survival benefit for patients treated with nivolumab compared with docetaxel. In that trial, 272 patients with metastatic SQ NSCLC patients had been randomized to receive nivolumab (n = 135) or docetaxel (n = 137). Median overall survival was 9.2 months for patients randomized to nivolumab and 6.0 months for those randomized to docetaxel (hazard ratio, 0.59; 95% CI, 0.44-0.79; P chemotherapy. The approval provides an important treatment option for these patients, affecting routine care and clinical trials.

  13. A patient with squamous cell carcinoma developing as a secondary cancer after radiation therapy and carbon dioxide snow-freezing therapy

    International Nuclear Information System (INIS)

    Yoshida, Akihiro; Miki, Hirotoshi; Yokoyama, Toshiya; Katori, Nobutada

    2004-01-01

    We report on a 59-year-old male who developed skin cancer many years after receiving radiation therapy and carbon dioxide snow-freezing therapy. About 50 years ago, the patient underwent radiation therapy and carbon dioxide snow-freezing therapy for nevus of the Ota of the left buccal region, the orbital region, and the forehead (fractional dose and total dose unknown). About 6 months prior to evaluation at this hospital, the patient noted tumor growth on the skin in the areas previously treated, and protruding lesions were observed on the left buccal region, the orbital region, and the forehead. Histopathological examination showed squamous cell carcinoma. At surgery, protruding lesions and scar tissue were completely excised, and split-thickness skin graft was used in the areas of skin loss. After 2 years of follow-up, no local recurrence or metastasis has been observed. (author)

  14. A comparative study of preoperative B-V-M-M chemotherapy and irradiation in advanced squamous cell cancer of the oral cavity

    International Nuclear Information System (INIS)

    Olasz, L.; Kwashie, F.; Herzegh, P.; Bruncsics, Z.; Hrovath, A.; Kiralyfalvi, L.

    1996-01-01

    From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery. Another group of 50 patients, who matched in risk factors and stage of disease, were treated with preoperative chemotherapy and surgery. Chemotherapy consisted of bleomycin, vincristine, mitolactol and methotrexate. All patients received 3 courses. Surgery was performed 2-3 weeks post-chemotherapy or 4-6 weeks post-radiotherapy. Forty four percent of the patients in the radiotherapy group showed recurrences, while 30% of the patients had recurrence in the chemotherapy group. The overall 3-year survival rate was 66% in the chemotherapy group and 57% in the radiation therapy group, with no statistical difference. (author)

  15. Effect of concomitant use of immunomodulator (OK-432 and/or PSK) on advanced lung cancer (squamous cell carcinoma and adenocarcinoma) treated with radiation with combined chemotherapy

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Kimura, Shuji; Imajo, Yoshinari

    1982-01-01

    Between 1975 and 1979, 209 cases of primary lung cancer admitted to the department of radiology were treated with radiation with combined chemotherapy. OK-432 and/or PSK as an immunomodulator was administered to 130 of these cases, and survival curves were evaluated between the patients with OK-432 and/or PSK and those without immunomodulator. In 61 cases (squamous cell carcinoma and adenocarcinoma) in stage III (UICC, 1978), fifty percent survival period was found to be 12.5 months for 16 cases with OK-432, 13.5 months for 9 cases with OK-432 and PSK, 9.0 months for 18 cases with PSK, and 8.0 months for 18 cases without immunotherapy, respectively. (author)

  16. Tafazzin (TAZ promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis.

    Directory of Open Access Journals (Sweden)

    Mei Chen

    Full Text Available Tafazzin (TAZ is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27, high-grade squamous intraepithelial lesions (HSIL, n = 26 and squamous cervical carcinoma (SCC, n = 41 by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

  17. Clinical utility and prospective comparison of ultrasonography and computed tomography imaging in staging of neck metastases in head and neck squamous cell cancer in an Indian setup

    International Nuclear Information System (INIS)

    Ashraf, M.; Biswas, J.; Jha, J.; Nayak, S.; Singh, V.; Majumdar, S.; Bhowmick, A.; Dam, A.

    2011-01-01

    Preoperative lymph node screening of all neck compartments is favored by clinicians for the management of the neck. The presence of a metastatic node on one side of the neck reduces the 5-year survival rate to 50%, and the presence of a metastatic node on both sides of the neck reduces the 5-year survival rate to 25%. This study compared the evaluation of lymph node metastases by ultrasonography (USG) and computed tomography (CT) in patients with squamous cell cancer of the head and neck region. Five hundred and eighty-four patients with squamous cell cancer of the head and neck were prospectively evaluated for the presence of cervical lymph node metastases. All patients underwent clinical examination (palpation), USG and CT imaging. Neck dissection was performed in all the patients, and the results of the preoperative evaluation were correlated with the surgical and histopathological findings. Metastases in neck nodes were identified in 148 patients by histopathological examination. Doppler USG correctly identified 136 node-positive patients (n=148; sensitivity 91.8%, specificity 97%). CT imaging correctly identified 122 patients with metastatic lymph nodes (n=148; sensitivity 83%, specificity 93%). Positive predictive values of USG and CT imaging were 95.6% and 91.3%, respectively, whereas the negative predictive values of these two imaging studies were 95.4% and 89.6%, respectively. The accuracy and sensitivity of USG in detection of cervical lymph node metastases make it a potentially promising and cheap preoperative tool for staging neck node metastases and optimizing the treatment plan for surgeons, especially in countries such as India. (author)

  18. Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

    Science.gov (United States)

    Demarco, Maria; Lorey, Thomas S; Fetterman, Barbara; Cheung, Li C; Guido, Richard S; Wentzensen, Nicolas; Kinney, Walter K; Poitras, Nancy E; Befano, Brian; Castle, Philip E; Schiffman, Mark

    2017-10-01

    The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

  19. Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance

    OpenAIRE

    Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

    2015-01-01

    Objective Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. Methods A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of ...

  20. Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

    Science.gov (United States)

    Scurry, James; Campion, Michael; Scurry, Bonnie; Kim, Soo Nyung; Hacker, Neville

    2006-04-01

    There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to carcinoma and, traditionally, is not graded. There are currently 3 grading systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial lesions, and the revised International Society for the Study of Vulvovaginal Disease (ISSVD) classification which has no grading of VIN. According to the ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category, simply termed warty-basaloid VIN. To determine the best system for grading warty-basaloid VIN and learn more about differentiated VIN, we reviewed the pathology of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN, 29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4 had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1 occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and because VIN 2 and 3 were difficult to distinguish and there appears little clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness of vulvar conditions, so that differentiated VIN is biopsied before cancer has supervened.

  1. Adenylyl cyclase-associated protein 1 in metastasis of squamous cell carcinoma of the head and neck and non-small cell lung cancer

    Science.gov (United States)

    Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Zavyalov, A. A.; Shishkin, D. A.; Kondakova, I. V.; Choinzonov, E. L.

    2016-08-01

    Progression of tumors and metastasis in particular is one of the main reasons of the high mortality rate among cancer patients. The primary role in developing metastases plays cell locomotion which requires remodeling of the actin cytoskeleton. Form, dynamics, localization and mechanical properties of the actin cytoskeleton are regulated by a variety of actin-binding proteins, which include the adenylyl cyclase-associated protein 1 (CAP1). The study is devoted to the investigation of CAP1 level depending on the presence or absence of metastases in patients with squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). The results show the contribution of CAP1 to SCCHN and NSCLC progression. We detected the connection between the tissue protein CAP1 level and the stage of NSCLC and SCCHN disease. Also the levels of the CAP1 protein in tissues of primary tumors and metastases in lung cancer were different. Our data showed that CAP is important in the development of metastases, which suggests further perspectives in the study of this protein for projecting metastasis of NSCLC and SCCHN.

  2. Src Family Kinases Mediate Betel Quid-Induced Oral Cancer Cell Motility and Could Be a Biomarker for Early Invasion in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jeff Yi-Fu Chen

    2008-12-01

    Full Text Available Betel quid (BQ-chewing oral cancer is a prevalent disease in many countries of Southeast Asia. Yet, the precise disease mechanism remains largely unknown. Here, we show that BQ extract-induced cell motility in three oral cancer cells (Ca9-22, SAS, and SCC9 presumably involves the Src family kinases (SFKs. Besides, BQ extract can markedly induce cell migration of wild type mouse embryonic fibroblasts (MEFs but not MEFs lacking three SFK members, namely, Src, Yes, and Fyn, indicating the requirement of SFKs for BQ-induced cell motility. Betel quid extract can also elevate cellular SFK activities because phosphorylation of tyrosine 416 at the catalytic domain is increased, which in turn promotes phosphorylation of an in vitro substrate, enolase. Furthermore, we identified that areca nut, a major component of BQ, is the key factor accounting for BQ-induced cell migration and invasion through SFKs-mediated signaling pathways. Immunohistochemistry revealed that, particularly in BQ-chewing cases, the activity of SFKs was significantly higher in tumor-adjacent mucosa than that in solid tumor areas (P < .01. These results suggest a possible role of SFKs in tumor-host interface and thus in early tumor invasion in vivo. Consistent with this is the observation that activation of SFKs is colocalized with invasive tumor fronts in oral squamous cell carcinoma. Together, we conclude that SFKs may represent a potential biomarker of invasion and therapeutic target in BQ-induced oral cancer.

  3. Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed.

    Science.gov (United States)

    Schwock, Joerg; Ko, Hyang Mi; Dubé, Valérie; Rouzbahman, Marjan; Cesari, Matthew; Ghorab, Zeina; Geddie, William R

    2016-01-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix. A detailed examination of preinvasive SMILE cases including a comparison of the cytologic features with usual-type adenocarcinoma in situ (AIS) and human papillomavirus (HPV) genotyping was performed. Excisions and preceding Papanicolaou (Pap) tests were retrieved from the files of 2 tertiary care centers. Histologic review estimated the lesional SMILE proportion. Pap tests were reviewed and assessed for architectural, cellular and background features. Cobas® HPV test was performed. 13 cases were identified. Mean/median patient age was 35/33 years (range 23-51 years). Concurrent high-grade squamous intraepithelial lesion was found in 10/13 (77%) and AIS in 8/13 (62%) cases. In 6 cases, SMILE was dominant (≥50%) and represented in 5/6 corresponding Pap tests. Cytology interpretations differed more often in the SMILE-dominant group (p < 0.05). SMILE and AIS had overlapping features. Feathering and prominent nucleoli were absent in SMILE. HPV DNA was detected in all 12 cases tested. HPV 18 was most common (7/12). Excisions with positive/suspicious margins were reported in 5/6 SMILE-dominant versus 3/7 nondominant cases. SMILE is best considered as an AIS variant for cytologic, etiologic and management purposes. Cytologic features overlap with AIS, but are more subtle and easily missed. HPV testing may play a role in facilitating SMILE detection. © 2016 S. Karger AG, Basel.

  4. Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-08-23

    Head and Neck Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharynx Carcinoma; Recurrent Salivary Gland Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage III Major Salivary Gland Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage IV Nasopharyngeal Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma

  5. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nakamura, Ryosuke; Kayamori, Kou; Oue, Erika; Sakamoto, Kei; Harada, Kiyoshi; Yamaguchi, Akira

    2015-01-01

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  6. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Firdaus S Dhabhar

    Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

  7. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ryosuke [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Kayamori, Kou [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Oue, Erika [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Sakamoto, Kei [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Harada, Kiyoshi [Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan)

    2015-03-20

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  8. Basic evaluation of measurement of the serum level of squamous cell carcinoma-related antigen (SCC) and its value in following irradiated patients with cancer of the uterine cervix

    International Nuclear Information System (INIS)

    Obata, Yasunori; Tadokoro, Masanori; Kazato, Sadayuki

    1987-01-01

    The measuremet of the serum level of squamous cell carcinoma-related antigen (SCC) purified from liver metastasis of cancer of the uterine cervix by an RIA kit is basically evaluated. The results of sensitivity, the recovery test, dilution test and variance test are good enough for clinical application. In gynecological disorders, the possitive rate is high (62 % [29/47]) in patients with cancer of the uterine cervix. Furthermore, the rate and level are related with the clinical staging. The changes of the serum SCC level in irradiated patients with cancer of the uterine cervix were a good reflection of the effectiveness of the treatment. (author)

  9. Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report

    Directory of Open Access Journals (Sweden)

    Noone Robert

    2010-02-01

    Full Text Available Abstract Introduction High-grade anal intraepithelial neoplasia, also referred to as anal squamous carcinoma in-situ, or Bowen's disease of the anus, make up less than 1% of all digestive system cancers in the United States. The treatment of choice is surgical resection with anal mapping. However, this disease often recurs or persists, requiring additional surgery for these patients. This can compromise the anal sphincter leading to leakage. In this case report, we discuss the efficacy of radiation therapy as a modality to treat post-excisional recurrent Bowen's disease, which may prevent sphincter compromise, leading to improved quality of life. Case presentation An 84-year-old Caucasian woman presented with post-excisional persistent/recurrent squamous cell carcinoma in-situ. The initial lesion measured 3 cm in diameter on the right lateral side of the anal margin. A standard surgery consisting of wide local excision with anal mapping was performed. The margins were clear and our patient was followed up. Our patient recurred with a 1.2 × 0.8 cm lesion on the left anal verge extending to the anal canal. A biopsy along with mapping was done, and 2 of the 17 mapping specimens were positive for carcinoma in-situ, one in the anal canal. Due to the location of the positive anal mapping, and in order to prevent sphincter compromise on re-excision, our patient was offered definitive radiation therapy. Two years after radiation therapy, our patient showed no signs of recurrent disease and had good sphincter control. Conclusion Although the main treatment modality for treating persistent/recurrent Bowen's disease is surgery, an alternative approach using external beam radiation for CIS may be enough to provide a cure for some patients with recurrent disease.

  10. Colon cancer metastasis to the mandibular gingiva with partial occult squamous differentiation: A case report and literature review

    OpenAIRE

    Ren, Quan-Guang; Huang, Tao; Yang, Sheng-Li; Hu, Jian-Li

    2016-01-01

    Metastasis is the primary cause of death among patients with colon cancer. However, the number of available studies regarding oral cavity metastases from colon cancer is currently limited. We herein report an unusual case of a 60-year-old male patient who developed an oral cavity metastasis from colon cancer. A total of 12 clinical case studies reporting colon cancer metastases to the mandibular gingival region were also reviewed, with the aim to elucidate the clinical and pathological charac...

  11. Gingival squamous cell carcinoma: A diagnostic impediment

    Directory of Open Access Journals (Sweden)

    Rekha Rani Koduganti

    2012-01-01

    Full Text Available Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated.

  12. p16INK4A, p53, EGFR expression and KRAS mutation status in squamous cell cancers of the anus: Correlation with outcomes following chemo-radiotherapy

    International Nuclear Information System (INIS)

    Gilbert, Duncan C; Williams, Anthony; Allan, Kimberley; Stokoe, Joanna; Jackson, Tim; Linsdall, Suzanne; Bailey, Charles MH; Summers, Jeff

    2013-01-01

    Background and Purpose: Squamous cell carcinomas of the anal canal are associated with infection with Human Papilloma Viruses (HPVs). Chemo-radiotherapy (CRT) gives 70% 3-year relapse-free survival. Improved predictive markers and therapeutic options are required. Methods: Tumours from 153 patients treated with radical chemo-radiotherapy (50.4 Gy in 28 with concurrent Mitomycin and 5-Fluorouracil between 2004 and 2009) were retrieved and immunohistochemistry performed for p16 INK4A , p53 and EGFR and correlated with outcome. Primary and relapsed samples were analysed for mutations in KRAS. Results: 137/153 (89.5%) stained moderately or strongly for p16 INK4A . p16 INK4A correlated strongly with outcome. 37/137 patients demonstrating moderate/strong p16 INK4A expression relapsed (27.0%), as opposed to 10/16 (62.5%) with absent/weak staining (log rank test p INK4A negative tumours were more frequent in men. p16 INK4A negative patients had significantly worse overall survival (p INK4A is strongly associated with relapse in SCC of the anus and identifies patients with very poor rates of relapse-free and overall survival. Primary and recurrent anal cancer expresses wild type KRAS, unaffected by treatment, supporting trials targeting EGFR in poor risk/recurrent anal cancer

  13. Definitive intensity-modulated radiotherapy concurrent with systemic therapy for oropharyngeal squamous cell carcinoma: Outcomes from an integrated regional Australian cancer centre.

    Science.gov (United States)

    Masoud Rahbari, Reza; Winkley, Lauren; Hill, Jacques; Tahir, Abdul Rahim Mohammed; McKay, Michael; Last, Andrew; Shakespeare, Thomas P; Dwyer, Patrick

    2016-06-01

    Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased over the past two decades largely because of an increase in human papilloma virus (HPV)-related OPSCC. We report here outcomes of definitive radiation therapy for OPSCC with simultaneous integrated boost intensity-modulated radiotherapy (IMRT) in a regional Australian cancer centre. We retrospectively reviewed electronic medical records (EMR) of all patients treated with IMRT for head and neck cancer. We included patients who received a curative intent IMRT for OPSCC (2010-2014). Of 61 patients, 80% were men, and the median age was 57 years. Ninety percent of our patients received concurrent systemic therapy, and 68% were p16 positive. The median radiotherapy dose received was 70 Gy in 35 fractions. The median follow up for surviving patients was 22 months. Twenty-four month actuarial data show that the loco-regional recurrence free, metastasis-free MFS, cancer-specific (CaSS) and overall survival percentages were 98.3%, 92.6%, 91% and 90.3%, respectively. We did not observe grades 4 or 5 acute or late toxicities, and 10 patients (16.2%) exhibited persistent grade 3 toxicity 6 months after completing the treatment. The results from curative IMRTs for OPSCC delivered in a regional cancer centre are comparable with results published by tertiary referral centres. A long-term follow up of this patient cohort will continue for further analyses and comparisons with tertiary centres. © 2016 The Royal Australian and New Zealand College of Radiologists.

  14. Serous endometrial intraepithelial carcinoma: a case series and literature review

    International Nuclear Information System (INIS)

    Pathiraja, P; Dhar, S; Haldar, K

    2013-01-01

    Minimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC. We report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice. Pure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients

  15. Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

    OpenAIRE

    Wang, Zhihui; Trope, Claes G; Fl?renes, Vivi Ann; Suo, Zhenhe; Nesland, Jahn M; Holm, Ruth

    2010-01-01

    Background CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. ...

  16. Ursolic Acid Florotriazole Treatment Causes Inhibition of Squamous ...

    African Journals Online (AJOL)

    observed malignant tumor of mucosa lining of the oral cavity. In Korea squamous cell carcinoma accounts for more than 90 % of the detected malignant tumors of the oral cavity [1]. Despite advancement in the fields of chemotherapy, radiation therapy and surgery, the prognosis of oral squamous cell cancer patients remains ...

  17. Squamous cell carcinoma of penis in patient with incipient neurosyphilis

    Directory of Open Access Journals (Sweden)

    D. V. Zaslavsky

    2016-01-01

    Full Text Available Squamous cell carcinoma of the skin (SSCC is one of the most common malignant skin tumors. Syphilis is a sexually transmitted disease caused by Treponema pallidum, with human beings as the only host. The combination of syphilis and squamous cell carcinoma of the skin is not uncommon, particularly if the lesions are located on different parts of the body. However, simultaneous development of the chancre and squamous cell carcinoma of the glans penis seems exceptional. Considering rarity of the manifestation observed we feel the rare case of combined syphilis and squamous cell skin cancer is of interest.

  18. Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Ma, Hongxia; Wang, Li-E; Liu, Zhensheng; Sturgis, Erich M; Wei, Qingyi

    2011-01-01

    Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN. We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population. Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (P trend = 0.046), particularly for non-oropharyngeal tumors (P trend = 0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR = 1.29, 95% CI = 1.01-1.64; AG/GG vs. AA: adjusted OR = 1.30, 95% CI = 1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR = 0.54, 95% CI = 0.34-0.86; TG/GG vs. TT: adjusted OR = 0.76, 95% CI = 0.61-0.95). Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers

  19. Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design.

    Science.gov (United States)

    Lal, Rohit; Bourayou, Nawel; Hillerdal, Gunnar; Nicolson, Marianne; Vikstrom, Anders; Lorenzo, Maria; D'yachkova, Yulia; Barriga, Susana; Visseren-Grul, Carla

    2013-10-03

    Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0-1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design

  20. HUMAN PAPILLOMA VIRUS IN THE ABNORMAL SQUAMOUS CELLS AND MILDY DYSKARYOTIC CELLS

    Directory of Open Access Journals (Sweden)

    Eda Vrtačnik Bokal

    2003-12-01

    Full Text Available Background. A persistent infection with high-risk genotypes of human papilloma viruses (HPV represents the most important etiologic factor for the development of cervical cancer, the second most frequent cancer in women in Slovenia as well as elsewhere in the world. In the detection of precancerous lesions the cervical Papanicolaou (Pap smear screening is used in Slovenia and worldwide. Management of patients with repeat abnormal smears (Pap II represents a great and complex clinical and public health problem; repeat cytologic examinations are the routine procedure in many countries, also in Slovenia, although the sensitivity of Pap smear testing in the detection of cervical intraepithelial neoplasms (CIN II and III is relatively low. In cases of abnormal squamous cells and mildly dyskaryotic cells the presence of infections with high-risk HPV genotypes is being increasingly used as a complementary method to Pap smear testing.Methods and patients. In the study we enrolled 148 women who within two years had three subsequent Pap II smears (abnormal squamous cells or mildly dyskaryotic cells. The prevalence of HPV infections was determined using three molecular tests: Hybrid Capture II (HCII (Digene Corporation, Gaithersburg, USA and two variants of polymerase chain reaction (PCR-PGMY11/PGMY09 and PCR-CPI/CPIIG. HPV genotypes were determined using the method of enzyme restriction of PCR products multiplied by group-specific oligonucleotid primers PGMY11/PGMY09.Results. HPV infection was detected in 25.7% of women. In women aged ≤ 30 years a statistically significantly higher incidence of HPV infections was found (37.8% than in women aged ≥ 30 years (20.4%. In women aged ≤ 30 years most frequent infections, and also equally distributed, were the ones with high-risk genotypes HPV 16 and HPV 73 and with a potentially high-risk genotype HPV 26. In women aged ≥ 30 years most frequent infections, and also equally distributed, were the ones with

  1. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

    Science.gov (United States)

    de Sanjosé, Silvia; Alemany, Laia; Ordi, Jaume; Tous, Sara; Alejo, Maria; Bigby, Susan M; Joura, Elmar Armin; Maldonado, Paula; Laco, Jan; Bravo, Ignacio G; Vidal, August; Guimerà, Núria; Cross, Paul; Wain, Gerard V; Petry, Karl Ulrich; Mariani, Luciano; Bergeron, Christine; Mandys, Václav; Sica, Adela Rosa; Félix, Ana; Usubutun, Alp; Seoud, Muhieddine; Hernández-Suárez, Gustavo; Nowakowski, Andrzej Marcin; Wilson, Godfrey; Dalstein, Veronique; Hampl, Monika; Kasamatsu, Elena Sachiko; Lombardi, Luis Estuardo; Tinoco, Leopoldo; Alvarado-Cabrero, Isabel; Perrotta, Myriam; Bhatla, Neerja; Agorastos, Theodoros; Lynch, Charles F; Goodman, Marc T; Shin, Hai-Rim; Viarheichyk, Halina; Jach, Robert; Cruz, M O L Eugenia; Velasco, Julio; Molina, Carla; Bornstein, Jacob; Ferrera, Annabelle; Domingo, Efren Javier; Chou, Cheng-Yang; Banjo, Adekunbiola F; Castellsagué, Xavier; Pawlita, Michael; Lloveras, Belén; Quint, Wim G V; Muñoz, Nubia; Bosch, F Xavier

    2013-11-01

    Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-01-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm 3 , and patients with a tumor volume 3 had a significantly better prognosis than those with a tumor volume >35 cm 3 at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume 3 had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = 3 larger than tumors without locoregional failure (p = .028) and 27.1-cm 3 larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

  3. Clinical and radiological characteristics of central pulmonary adenocarcinoma: a comparison with central squamous cell carcinoma and small cell lung cancer and the impact on treatment response

    Directory of Open Access Journals (Sweden)

    Wang Z

    2018-05-01

    Full Text Available Zhe Wang,1,2 Minghuan Li,2 Yong Huang,3 Li Ma,3 Hui Zhu,2 Li Kong,2 Jinming Yu2 1School of Medicine, Shandong University, Jinan, Shandong, China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China; 3Department of Radiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China Purpose: The proportion of central pulmonary adenocarcinoma (ADC in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs and squamous cell carcinomas (SQCCs and investigated the impact of these characteristics on patients’ treatment response. Patients and methods: The medical records of 302 consecutive patients with central lung cancer from July 2014 to September 2016 were retrospectively reviewed. There were 99 patients with ADC, 95 with SQCC and 108 with SCLC. Computed tomography images were interpreted by two radiologists. Treatment response was determined by Response Evaluation Criteria In Solid Tumors 1.1. Results: Univariate analyses found that younger age, female sex, no history of smoking, higher levels of carcinoembryonic antigen (CEA, contralateral hilum lymphadenopathy, contralateral lung metastasis, pleural nodules and pleural metastasis to the interlobular fissure were significantly correlated with central ADC. Multivariate logistic regression analyses revealed that compared with central SQCC, female sex, younger age, no history of smoking, higher levels of CEA and contralateral hilum lymphadenopathy were the significantly independent indicators of central pulmonary ADC. Furthermore, compared with central SCLC, younger age, higher levels of CEA and cytokeratin 19 fragment (Cyfra21-1, lower

  4. Frequency of cervical intraepithelial neoplasia treatment in a well-screened population

    DEFF Research Database (Denmark)

    Barken, Sidsel Svennekjaer; Rebolj, Matejka; Andersen, Erik Søgaard

    2012-01-01

    Treatment of cervical intraepithelial neoplasia (CIN) detectable at screening has helped reduce the incidence of cervical cancer, but has also led to overtreatment. The estimates of overtreatment have often focused on a particular grade of CIN or age group. The aim of this paper was to provide...... a nationwide population-based estimate of the frequency of CIN treatment per prevented cervical cancer case in a well-screened population. We retrieved the data from the Danish National Population, Patient, Health Insurance, Pathology, and Cancer Registers, and calculated annual age-standardized CIN treatment...... rates. We estimated the frequency of CIN treatment per prevented cervical cancer case by comparing the cumulative life-time risk of CIN treatment from 1996 onward, with the difference in the cumulative life-time risks of cervical cancer in the prescreening and the screening periods. Since 1996, more...

  5. Photodynamic therapy of cervical intraepithelial neoplasia

    Science.gov (United States)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  6. Colon cancer metastasis to the mandibular gingiva with partial occult squamous differentiation: A case report and literature review.

    Science.gov (United States)

    Ren, Quan-Guang; Huang, Tao; Yang, Sheng-Li; Hu, Jian-Li

    2017-02-01

    Metastasis is the primary cause of death among patients with colon cancer. However, the number of available studies regarding oral cavity metastases from colon cancer is currently limited. We herein report an unusual case of a 60-year-old male patient who developed an oral cavity metastasis from colon cancer. A total of 12 clinical case studies reporting colon cancer metastases to the mandibular gingival region were also reviewed, with the aim to elucidate the clinical and pathological characteristics of this disease entity in order to improve clinical diagnosis and treatment. It was demonstrated that patients with oral cavity metastases from colon cancer were predominantly in the sixth or seventh decades of life. The mandible was the main site of metastatic tumors to the oral cavity, while the occurrence of gingival metastases was comparatively rare. Moreover, the diagnoses of an oral metastatic tumor and primary colon cancer were often synchronous and were frequently accompanied with metastases to other organs. Several key aspects were suggested that should be accounted for when diagnosing colon cancer patients, including focusing attention to oral symptoms when examining cancer patients, utilizing a multidisciplinary approach for differential diagnosis and utilizing postoperative pathological examination to accurately diagnose the type of tumor and optimize the efficacy of treatment.

  7. Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

    2017-11-01

    We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  8. Long term follow up results of serum squamous cell carcinoma antigen level in uterine cervix cancer treated by radiotherapy

    International Nuclear Information System (INIS)

    Yun, Hyong Geun

    2003-01-01

    To evaluate the long term significance of the squamous cell carcinoma (SCC) antigen (Ag) as a tumor marker in uterine cervix carcinoma. The SCC antigen levels of pre-radiotherapy and serial post-radiotherapy serum were analyzed in 48 patients who received radiotherapy with histologically proven primary SCC of the uterine cervix. Pre-radiotherapy SCC Ag level was high (≥2 ng/ml) at 79.2%. After the treatment, the SCC Ag level was significantly decreased. The SCC Ag level measured at about 3 months after radiotherapy was high at 23.0%. In further follow up measurements, a rise of the SCC Ag to a high level was well associated with clinical relapse. The specificity of the elevated SCC Ag level in association with recurrent or persistent disease was 100%, and the sensitivity was 85.7%. In 3 of 4 lung metastasis cases, lung lesions were detected in chest PA before elevation of the SCC Ag level. The median lead time of the high SCC Ag level to clinical recurrence was 4 months. SCC Ag was a good tumor marker for monitoring treatment effect in patients with increased pre-treatment levels except in case of early lung metastasis. Elevation of the SCC Ag level after radiotherapy accurately predicted the treatment failure with lead time of 4 months. But, in early lung metastasis cases, the SCC level may be normal temporarily. Thus, chest PA should be checked to evaluate the presence of lung metastasis

  9. Multivariate analysis of the prognostic factors of squamous cell cervical cancer treated by radical hysterectomy or combined radiation therapy

    International Nuclear Information System (INIS)

    Coelho, Francisco Ricardo Gualda; Kowalski, Luiz Paulo; Abrao, Fauzer Simao; Franco, Eduardo Luiz; Zeferino, Luiz Carlos; Brentani, Maria Mitzi

    1996-01-01

    Six hundred and nine cases of invasive squamous cell carcinoma of the cervix uteri in a retrospective analysis (1953-1982) at the A.C. Camargo Hospital, Antonio Prudente Foundation, Sao Paulo, Brazil. The patients were submitted to radical surgery and radiation therapy, individually or in combination. A multivariate analysis of the different variables were performed according to the Cox's regression method. The variables of prognosis value, in decreasing order of importance, were: the decade of patient's admission, the modality of therapy employed, the presence of residual tumor in the surgical specimens and the clinical stage of the disease. Other variables like ethnic group, age of first menstrual flux, menopause, number of pregnancy, kind of delivery, number and kind of abortion, were found to be of no prognostic importance. The decade of admission was of independent prognostic significance. The presence of residual tumor in the surgical specimens was more important than lymph nodes spreading, but the overall survival was affected by the increase in the number of positive lymph nodes. Patient's age was a weak prognostic factor accounting for a reduction in the survival time among cases with age upper to 45 years old. Radiation therapy sterilizes a considerable number of lymph nodes but not all of them in every patient. There are a specific group of patients where the radical surgery is necessary in order to carry a complete debulking of the disease. (author)

  10. A trial of radiofrequency ablation for anal intraepithelial neoplasia.

    Science.gov (United States)

    Goldstone, Robert N; Hasan, Shirin R; Drury, Steven; Darragh, Teresa M; van Zante, Annemieke; Goldstone, Stephen E

    2017-03-01

    Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

  11. Fatal Necrotizing Encephalopathy after Treatment with Nivolumab for Squamous Non-Small Cell Lung Cancer: Case Report and Review of the Literature

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    Markus Leitinger

    2018-01-01

    Full Text Available Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab. Nivolumab targets the immune-check point inhibitor programmed cell death-1 and was used for squamous non-small cell lung cancer. Partly reversible neurologic and psychiatric symptoms and unremarkable brain magnetic resonance imaging (MRI were observed after the first course. Neurological symptoms progressed and recurrent seizures developed after the second course. Brain MRI disclosed multiple edematous and confluent supra- and infratentorial lesions, partly with contrast-enhancement. We excluded autoimmune and paraneoplastic causes and performed ancillary investigations to rule out common and opportunistic infections. Eventually, postmortem histopathological analysis of the brain revealed a necrotizing process, which contrasts previous cases reporting parenchymal immune cell infiltration or demyelination. Appropriate diagnostic pathways and treatment algorithms need to be implemented for the work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment.

  12. Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells.

    Science.gov (United States)

    Kinoshita, M; Matsuda, Y; Arai, T; Soejima, Y; Sawabe, M; Honma, N

    2018-02-01

    Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast. We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background. SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, Pstreaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice. © 2017 John Wiley & Sons Ltd.

  13. Serendipitous discovery of potent human head and neck squamous cell carcinoma anti-cancer molecules: A fortunate failure of a rational molecular design.

    Science.gov (United States)

    Zagni, Chiara; Pistarà, Venerando; Oliveira, Luciana A; Castilho, Rogerio M; Romeo, Giovanni; Chiacchio, Ugo; Rescifina, Antonio

    2017-12-01

    Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity. Surprisingly, compounds 1a and 12, this last exclusively obtained in place of 1d, exhibited a very low HDAC inhibitory activity. A serendipitous assay of these two compounds, conducted on three chemoresistant cell lines of head and neck squamous cell carcinoma (HNSCC), showed their antiproliferative activity at low nanomolar concentrations, better than cisplatin. In vitro, biological assays indicated that compounds 1a and 12 are able to increase acetylation of histone H3 and to interfere with the PI3K/Akt/mTOR pathway by inducing the accumulation of PTEN protein. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

    Science.gov (United States)

    Yang, Frances Fan

    Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved

  15. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

    Science.gov (United States)

    de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

    2015-11-01

    Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Next-Generation Sequencing of Tubal Intraepithelial Carcinomas.

    Science.gov (United States)

    McDaniel, Andrew S; Stall, Jennifer N; Hovelson, Daniel H; Cani, Andi K; Liu, Chia-Jen; Tomlins, Scott A; Cho, Kathleen R

    2015-11-01

    High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs, or more specifically, STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. We performed targeted next-generation sequencing (NGS) on formalin-fixed, paraffin-embedded tissue from 4 women, 2 with HGSC and 2 with uterine endometrioid carcinoma (UEC) who were diagnosed as having synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal association between these lesions. Next-generation sequencing confirmed the presence of a STIC clonally unrelated to 1 case of UEC, and NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. We demonstrate that targeted NGS can identify genetic alterations in minute lesions, such as TICs, and confirm TP53 mutations as early driving events for HGSC. Next-generation sequencing also demonstrated unexpected associations between presumed STICs and synchronous carcinomas, providing evidence that some TICs are actually metastases rather than HGSC precursors.

  17. High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

    Science.gov (United States)

    Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

    2012-01-01

    Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

  18. Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced non-squamous non-small cell lung cancers

    Science.gov (United States)

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A.; Gettinger, Scott N.

    2016-01-01

    Structured Abstract Purpose The addition of bevacizumab, an anti-angiogenesis agent, to cytotoxic chemotherapy improves survival in patients with advanced non-squamous non-small cell lung cancers (nsNSCLCs). Regorafenib is an oral multi-targeted kinase inhibitor with potent anti-angiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. This phase I trial evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Methods Chemotherapy-naïve patients with advanced nsNSCLCs were treated with regorafenib 60mg/day continuously and cisplatin 75mg/m2 plus pemetrexed 500mg/m2 once every three weeks for up to six cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled prior to premature termination of the study due to slow recruitment and a change in the development strategy of regorafenib by the study sponsor, partially due to slow enrollment. Five patients experienced at least one treatment-related Grade 3 adverse event. No grade 4–5 toxicity occurred. 5 of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range 1.5–15.1). Minor pharmacokinetic (PK) interactions between regorafenib and chemotherapy were observed. Conclusions Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naïve patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. PMID:26003007

  19. High Numbers of Stromal Cancer-Associated Fibroblasts Are Associated With a Shorter Survival Time in Cats With Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Klobukowska, H J; Munday, J S

    2016-11-01

    Cancer-associated fibroblasts (CAFs) are fibroblastic cells that express α-smooth muscle actin and have been identified in the stroma of numerous epithelial tumors. The presence of CAFs within the tumor stroma has been associated with a poorer prognosis in some human cancers, including oral squamous cell carcinomas (SCCs). Cats frequently develop oral SCCs, and although these are generally highly aggressive neoplasms, there is currently a lack of prognostic markers for these tumors. The authors investigated the prognostic value of the presence of CAFs within the stroma of oral SCC biopsy specimens from 47 cats. In addition, several epidemiologic, clinical, and histologic variables were also assessed for prognostic significance. A CAF-positive stroma was identified in 35 of 47 SCCs (74.5%), and the median survival time (ST) of cats with CAF-positive SCCs (35 days) was significantly shorter than that of cats with CAF-negative SCCs (48.5 days) (P = .031). ST was also associated with the location of the primary tumor (P = .0018): the median ST for oropharyngeal SCCs (179 days) was significantly longer than for maxillary (43.5 days; P = .047), mandibular (42 days; P = .022), and sublingual SCCs (22.5 days; P = .0005). The median ST of sublingual SCCs was also shorter compared with maxillary SCCs (P = .0017). Furthermore, a significant association was identified between site and the presence of stromal CAFs (P = .025). On the basis of this retrospective study, evaluating the tumor stroma for CAFs in feline oral SCC biopsy specimens may be of potential prognostic value. © The Author(s) 2016.

  20. An overview on "cellular cannibalism" with special reference to oral squamous cell carcinoma.

    Science.gov (United States)

    Jain, M

    2015-12-01

    Cellular cannibalism has been defined as a large cell engulfing a slightly smaller one within its cytoplasm. It has been described in various cancers like bladder cancer, breast cancer, lung cancer, gastric cancer, oral squamous cell carcinoma. Cellular cannibalism has been well correlated with anaplasia, tumor aggressiveness, grading and metastatic potential. Present review focuses on significance of cannibalism in relation to cancer with special emphasis on oral squamous cell carcinoma.

  1. Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

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    Xiaoao Pang

    2014-05-01

    Full Text Available We investigated the significance of high- mobility group box1 (HMGB1 and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3, IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN, and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05. In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05. HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05. HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05. Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.

  2. Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung squamous cell cancer: a case report

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    Hong Li

    2017-02-01

    Full Text Available Abstract Background Programmed cell death 1 (PD-1 and its ligand 1 (PD-L1 inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB corresponding to 95–96 percentile in lung SCC, i.e., 87.4–91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs. One potential TAA candidate is telomerase reverse transcriptase (TERT in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I

  3. Atypical squamous cells, cannot exclude high grade squamous intraepithelial (ASC-H in HIV-positive women

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    Michelow Pam

    2010-01-01

    Full Text Available Objective: South Africa has very high rates of both HIV infection and cervical pathology. The management of ASC-H is colposcopy and directed biopsy, but with so many women diagnosed with HSIL and a dearth of colposcopy centres in South Africa, women with cytologic diagnosis of ASC-H may not be prioritized for colposcopy. The aim of this study was to determine if HIV-positive women with a cytologic diagnosis of ASC-H should undergo immediate colposcopy or whether colposcopy can be delayed, within the context of an underfunded health care setting with so many competing health needs. Materials and Methods: A computer database search was performed from the archives of an NGO-administered clinic that offers comprehensive HIV care. All women with a cytologic diagnosis of ASC-H on cervical smears from September 2005 until August 2009 were identified. Histologic follow up was sought in all patients. Results: A total of 2111 cervical smears were performed and 41 diagnosed as ASC-H (1.94%. No histologic follow up data was available in 15 cases. Follow up histologic results were as follows: three negative (11.5%, five koilocytosis and/ or CIN1 (19.2%, ten CIN2 (38.5% and eight CIN3 (30.8%. There were no cases of invasive carcinoma on follow up. Conclusion: The current appropriate management of HIV-positive women in low-resource settings with a diagnosis of ASC-H on cervical smear is colposcopy, despite the costs involved. In the future and if cost-effective in developing nations, use of novel markers may help select which HIV-positive women can be managed conservatively and which ones referred for more active treatment. More research in this regard is warranted.

  4. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

    International Nuclear Information System (INIS)

    Garcia-Iglesias, Trinidad; Daneri-Navarro, Adrian; Toro-Arreola, Alicia del; Albarran-Somoza, Benibelks; Toro-Arreola, Susana del; Sanchez-Hernandez, Pedro E; Ramirez-Dueñas, Maria Guadalupe; Balderas-Peña, Luz Ma. Adriana; Bravo-Cuellar, Alejandro; Ortiz-Lazareno, Pablo C

    2009-01-01

    Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression

  5. The expression of podoplanin protein is a diagnostic marker to distinguish the early infiltration of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Chen, Guangyong; Xu, Rui; Yue, Bing; Mei, Xue; Li, Peng; Zhou, Xiaoge; Huang, Shoufang; Gong, Liping; Zhang, Shutian

    2017-03-21

    The esophageal squamous cell carcinoma (ESCC) is usually develped from low-grade intraepithelial neoplasia (LGIEN) and high-grade intraepithelial neoplasia (HGIEN) to infiltrative squamous cell carcinoma. Till now, it remains hard to screen for infiltration at earlier stages, especially the differentiation between HGEIN and early infiltrative carcinoma. The purpose of this study is to determine a role of podoplanin in differentiating between HGEIN and early infiltrative squamous cell carcinoma. Totally 133 patients pathologically diagnosed with early ESCC and/or precancerous lesions were enrolled.The EnVision two-step IHC staining technique was applied using the monoclonal mouse anti-human Podoplanin antibody (clone number: D2-40). The expressions of PDPN protein on the basal layer of squamous epithelium lesions could be divided into three different patterns: complete type, incomplete (non-continuous) type, or missing type. A diagnosis of HGEIN can be made if the basal layer showed non-continuous or complete expression of PDPN and a diagnosis of early infiltration can be made if the expression of PDPN is completely missing. Our study confirmed that PDPN was a potential biomarker to identify the presence of early infiltrative squamous cell carcinoma.

  6. The detection of hTERC amplification using fluorescence in situ hybridization in the diagnosis and prognosis of cervical intraepithelial neoplasia: a case control study

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    Yin Geping

    2012-08-01

    Full Text Available Abstract Background Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN and cervical cancer are Thinprep cytology test (TCT and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients’ prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC in the diagnosis and prognosis of CIN. Methods The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11 or radical surgery (n = 14. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH, and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. Results The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% ± 4.6% and 44.4% (12/27 respectively in patients with CIN I; 16.0% ± 14.4% and 85.1% (46/54 in patients with CIN II/III; 19.7% ± 13.3% and 88.3% (15 /17 in patients with carcinoma in situ; 47.0% ± 25.2% and 100% (28/28in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P Conclusion The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.

  7. Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.

    Directory of Open Access Journals (Sweden)

    Hannah P Yang

    Full Text Available Cervical intraepithelial neoplasia grade 3 (CIN3, the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.CIN3 cases varied substantially by size (1-10 LEEP segments and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.

  8. Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Munk, Christian; Nielsen, Thor Schütt Svane

    2015-01-01

    the Danish incidence trends during 1997-2011 when cervical screening coverage was high. Incidences of cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) were also assessed, with the latest part of the study period coinciding with introduction of free-of-charge human......PURPOSE: The incidence of cervical cancer, including squamous cell carcinoma (SCC), has been decreasing in several developed countries since the onset of organized screening programs; in some countries, however, the incidence of adenocarcinoma has increased among young women. We investigated......, importantly, they decreased significantly during 2009-2012 in women aged ≤20 years. CONCLUSIONS: The Danish screening program has successfully reduced the incidence of cervical cancer, especially of SCC in older women; however, the program has not significantly reduced the incidence in young women...

  9. More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells

    International Nuclear Information System (INIS)

    Zhang, Si-yang; Hui, Lin-ping; Li, Chun-yan; Gao, Jian; Cui, Ze-shi; Qiu, Xue-shan

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. The purpose of this study was to explore the function of BDNF in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The expression of BDNF was examined in 110 samples of lung SCC and ADC by immunohistochemistry. The protein level of BDNF was examined in 25 lung SCC or ADC samples and paired non-tumors by western blot. BDNF expression was also evaluated in human bronchial epithelial cells (HBE) and 4 lung cancer cell lines using western blot. Three BDNF mRNA variants containing exons IV, VI and IX were evaluated in HBE, two SCC (SK, LK2) and two ADC (A549, LTE) cell lines by RT-PCR. The expression and secretion of BDNF were also determined in cells using western blot and ELISA. Then the shRNA specific for BDNF was transfected into LK2 or A549 cells to further elucidate the BDNF knockdown on cell proliferation, apoptosis and invasion, which were confirmed by MTT, flow cytometry and transwell examinations. 71.8 % (79 out of 110) of lung SCC and ADC samples were detected positive BDNF, and high expression of BDNF was significantly correlated with histological type and T stage. Compared with non-tumorous counterparts, BDNF was apparently overexpressed in SCC and ADC tissues. In cell studies, the extensive expression and secretion of BDNF were demonstrated in lung cancer cells compared with HBE cells. Interestingly, the expressions of BDNF mRNA variant IV and VI were identical in all cells examined. However, more expression of BDNF mRNA variant IX was found in SK and LK2 cells. The apoptotic cells were increased, and the cell proliferation and invasion were both attenuated once the expression of BDNF was inhibited. When retreated by rhBDNF, BDNF knockdown cells showed less apoptotic or more proliferative and invasive. Our data show that BDNF probably facilitates the tumorigenesis of lung SCC and ADC. The expression of BDNF m

  10. Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients

    International Nuclear Information System (INIS)

    Miao, Liyun; Zhang, Deping; Liu, Hongbing; Song, Yong; Wang, Yongsheng; Zhu, Suhua; Shi, Minke; Li, Yan; Ding, Jingjing; Yang, Jun; Ye, Qing; Cai, Hourong

    2014-01-01

    Although many of the recently approved genomically targeted therapies have improved outcomes for patients in non–small-cell lung cancer (NSCLC) with lung adenocarcinoma, little is known about the genomic alterations that drive lung squamous cell cancer (SCC) and development of effective targeted therapies in lung SCC is a promising area to be further investigated. Discoidin domain receptor 2 (DDR2), is a novel receptor tyrosine kinases that respond to several collagens and involved in tissue repair, primary and metastatic cancer progression. Expression of DDR2 mRNA was analyzed in 54 lung SCC tissues by qRT-PCR. Over-expression approaches were used to investigate the biological functions of DDR2 and its’ mutations in lung SCC cells. Conventional Sanger sequencing was used to investigate the mutations of DDR2 gene in 86 samples. The effect of DDR2 and its’ mutations on proliferation was evaluated by MTT and colony formation assays; cell migration and invasion was evaluated by trasnwell assays. Lung SCC cells stably transfected with pEGFP-DDR2 WT, pEGFP-DDR2-S131C or empty vector were injection into nude mice to study the effect of DDR2 and its’ mutation on tumorigenesis in vivo. Protein and mRNA expression levels of E-cadherin and MMP2 were determined by qRT-PCR and western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). In this study, we found that DDR2 mRNA levels were significantly decreased in 54 lung SCC tissues compared with normal lung tissues. Moreover, there were 3 novel DDR2 mutations (G531V, S131C, T681I) in 4 patients and provide the mutation rate of 4.6% in the 86 patients with lung SCC. The mutation of S131C in DDR2 could promote lung SCC cells proliferation, migration and invasion via inducing MMP-2, but reducing E-cadherin expression. These data indicated that the novel DDR2 mutation may contribute to the development and progression of lung SCC and this effect may be associated

  11. Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thaís Santana Gastardelo

    Full Text Available The anti-inflammatory protein annexin A1 (ANXA1 has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26 (annexin A1 N-terminal-derived peptide, Boc2 (antagonist of FPR and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1(2-26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth

  12. Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.

    Science.gov (United States)

    Namani, Akhileshwar; Matiur Rahaman, Md; Chen, Ming; Tang, Xiuwen

    2018-01-06

    NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers. RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature. A signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways. Altogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with

  13. Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Gill, Beant S.; Viswanathan, Akila N.; Balasubramani, Goundappa K.; Sukumvanich, Paniti; Beriwal, Sushil

    2017-01-01

    Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical

  14. Diffusion-weighted MR imaging for postoperative nodal recurrence of esophageal squamous cell cancer in comparison with FDG-PET

    International Nuclear Information System (INIS)

    Shuto, Kiyohiko; Saito, Hiroshige; Ohira, Gaku

    2009-01-01

    We evaluated the power of diffusion-weighted MR imaging with background body signal suppression (DWIBS) in patients with postoperative lymph node recurrence of esophageal cancer and compared with fluorodeoxyglucose-positron emission tomography (FDG-PET) findings. Forty-seven suspected lesions by multi detector row CT (MDCT) were enrolled. No significant difference between DWIBS and PET was observed in sensitivity (95% vs 97%), positive predictive value (PPV) (83% vs 90%) and overall accuracy rate (81% vs 87%). The apparent diffusion coefficients (ADCs) (x 10 -3 mm 2 /s) of recurrent nodes, primary cancer and normal esophagus were 1.124, 1.058 and 2.079, respectively. ADCs of recurrent nodes were significantly lower than those of normal esophagus (p<0.0001). The cut-off ADC line of 1.5 revealed 100% overall accuracy for separating the recurrent lesion from normal esophagus. Noninvasive DWIBS may become a valid modality to discriminate nodal recurrence of esophageal cancer by no means inferior to PET. (author)

  15. Lower lip squamous cell carcinoma in patients with photosensitive disorders: Analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012.

    Science.gov (United States)

    Borges, J-F-P; Lanaro, N-D; Bernardo, V-G; Albano, R-M; Dias, F; de Faria, P-A-S; Pinto, L-F-R; Lourenço, S-Q-C

    2018-01-01

    Lower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC. Data from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package. The mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients. Photosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected.

  16. Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

    Science.gov (United States)

    Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

    2018-04-01

    This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Expression and Localization of Cathepsins B, D, and G in Two Cancer Stem Cell Subpopulations in Moderately Differentiated Oral Tongue Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Therese Featherston

    2017-07-01

    Full Text Available AimWe have previously demonstrated the putative presence of two cancer stem cell (CSC subpopulations within moderately differentiated oral tongue squamous cell carcinoma (MDOTSCC, which express components of the renin–angiotensin system (RAS. In this study, we investigated the expression and localization of cathepsins B, D, and G in relation to these CSC subpopulations within MDOTSCC.Methods3,3-Diaminobenzidine (DAB and immunofluorescent (IF immunohistochemical (IHC staining was performed on MDOTSCC samples to determine the expression and localization of cathepsins B, D, and G in relation to the CSC subpopulations. NanoString mRNA analysis and colorimetric in situ hybridization (CISH were used to study their transcripts expression. Enzyme activity assays were performed to determine the activity of these cathepsins in MDOTSCC.ResultsIHC staining demonstrated expression of cathepsins B, D, and G in MDOTSCC. Cathepsins B and D were localized to CSCs within the tumor nests, while cathepsin B was localized to the CSCs within the peri-tumoral stroma, and cathepsin G was localized to the tryptase+ phenotypic mast cells within the peri-tumoral stroma. NanoString and CISH mRNA analyses confirmed transcription activation of cathepsins B, D, and G. Enzyme activity assays confirmed active cathepsins B and D, but not cathepsin G.ConclusionThe presence of cathepsins B and D on the CSCs and cathspsin G on the phenotypic mast cells suggest the presence of bypass loops for the RAS which may be a potential novel therapeutic target for MDOTSCC.

  18. {sup 18}F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Manca, Gianpiero; Volterrani, Duccio [University Hospital of Pisa, Regional Center of Nuclear Medicine, Pisa (Italy); Vanzi, Eleonora [University Hospital of Siena, Service of Medical Physics, Siena (Italy); Rubello, Domenico; Grassetto, Gaia [Santa Maria della Misericordia Rovigo Hospital, Department of Nuclear Medicine, Rovigo (Italy); Giammarile, Francesco [Faculte Charles Merieux, Medecine Nucleaire, Centre Hospitalier and Biophysique, Lyon (France); Wong, Ka Kit [University of Michigan Hospital, Nuclear Medicine/Radiology Department, Ann Arbor, MI (United States); Nuclear Medicine Service, Department of Veterans Affairs Health System, Ann Arbor, MI (United States); Perkins, Alan C. [University of Nottingham, Department of Radiological Sciences, School of Medicine, Nottingham (United Kingdom); Colletti, Patrick M. [Southern University of California, Department of Radiology, Los Angeles, CA (United States)

    2016-07-15

    {sup 18}F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. {sup 18}F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of {sup 18}F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited ''quantification'' to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of ''true'' quantification. A discussion is then presented on how semiquantitative information is currently used in clinical {sup 18}F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and ''personalized'' quantification techniques. (orig.)

  19. BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9

    Directory of Open Access Journals (Sweden)

    Chou-Kit Chou

    2015-07-01

    Full Text Available BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC. However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK and human gingival fibroblasts (HGF. Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

  20. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

    Directory of Open Access Journals (Sweden)

    Ramon Andrade de Mello

    Full Text Available BACKGROUND: The use of cetuximab in combination with platinum (P plus 5-fluorouracil (F has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN. We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS, progression-free-survival (PFS, overall response rate (ORR and the treatment toxicity profile in a retrospective cohort. PATIENTS AND METHODS: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. RESULTS: The median patient age was 53 (37-78 years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316 and PFS of 8 months (CI 95%, 6.051-9.949. The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%, skin rash (3.8% and mucosistis (3.8%. CONCLUSIONS: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

  1. Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (78-02)

    International Nuclear Information System (INIS)

    Fazekas, J.T.; Goodman, R.L.; McLean, C.J.

    1981-01-01

    This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m 2 once per week, not to exceed 24 gm total cumulative in 6 weeks. The dosage was reduced to 2.0 gm/m 2 /wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies and an equal number developing nausea and/or vomiting following p.o. drug administration. Encephalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m 2 dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels. These preliminary results seemed sufficiently encouraging to warrant a Phase III (randomized) study, now underway by the RTOG

  2. Value of adjuvant misonidazole in the definitive irradiation of advanced head and neck squamous cancer: an RTOG pilot study (number78-02)

    International Nuclear Information System (INIS)

    Fazekas, J.T.; Goodman, R.L.; McLean, C.J.

    1981-01-01

    This RTOG Phase II trial was instituted to determine the toxicity and potential value of the electron-affinic agent, Misonidazole, adjunctive to definitive radiotherapy of T3 and T4 squamous cancers of the oral cavity, oropharynx, or hypopharynx. The fractionation schema was altered to deliver two separate treatments (250 rad and 210 rad) on each day when Misonidazole was administered, while maintaining relatively ''standard'' fractionation (5 fractions and 1000 rad per week). In order to achieve effective enhancement while minimizing toxicity, Misonidazole doses were limited to 2.5 gm/m 2 once per week, not to exceed 24 gm total cumulative in 6 weeks. Definitive radiation therapy in the range of 6500-7000 rad was delivered over 6 1/2-8 weeks. The dosage was reduced to 1.0 gm/m 2 /wk after the first 30 patients were entered. Among the 50 patients entered, toxicity was confined to the nervous system, with one-third of the patients experiencing mild or moderate peripheral neuropathies (paresthesias, numbness) and an equal number developing nausea and/or vomiting following p.o. drug administration. Encelphalopathy occurred in 10% of the 30 patients receiving 2.5 mg/m 2 dosage. Serum drug levels and cumulative Misonidazole doses did not correlate well with toxicity or response except in comparison of the ''no response'' to the ''complete response'' categories. Immediate mucosal and skin reactions were not enhanced and unusual late normal tissue effects were not encountered. Complete disappearance of all visible and palpable primary tumor was noted in 67% of the 36 patients who completed the adjuvant sensitizer program. Tumor response and survival did not generally correlate with measured (serum) Misonidazole concentration; recurrence was also independent of these measured levels

  3. Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Gandra S

    2015-01-01

    Full Text Available Sumanth Gandra, Aline Azar, Mireya WessolosskyDivision of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA, USABackground: Although anal high-risk human papillomavirus (HR-HPV infection and anal cytological abnormalities are highly prevalent among human immunodeficiency virus (HIV-infected men who have sex with men (MSM, there are insufficient data on these abnormalities among HIV-infected heterosexual men (HSM and women. In this study, we evaluated the prevalence of anal HR-HPV, cytological abnormalities, and performance of these screening tests in detecting high-grade anal intraepithelial neoplasia (AIN2+ among our cohort of HIV-infected MSM and non-MSM (HSM and women.Methods: A single-center, retrospective cohort study was conducted with HIV-infected individuals who underwent anal cancer screening with anal cytology and HR-HPV testing from January 2011 to January 31, 2013.Results: Screening of 221 HIV-infected individuals for both HR-HPV and anal cytology showed the presence of HR-HPV in 54% (abnormal anal cytology 48% of MSM, 28% (abnormal anal cytology 28% of HSM, and 27% (abnormal anal cytology 34% of women. Among 117 (53% individuals with abnormal results (HR-HPV-positive and/or cytology was atypical squamous cells of undetermined significance or above, 67 underwent high resolution anoscopy. Of these 67 individuals, 22 individuals had AIN2+ (17 MSM, four women, and one HSM. HR-HPV correlated better with AIN2+ than with anal cytology on biopsy in both MSM (r=0.29 versus r=0.10; P=0.05 versus P=0.49 and non-MSM (r=0.36 versus r=-0.34; P=0.08 versus P=0.09.Conclusion: Given the presence of AIN2+ in screened HIV-infected HSM and women, routine anal cancer screening in all HIV-infected individuals should be considered. HR-HPV merits further evaluation for anal cancer screening among non-MSM.Keywords: human immunodeficiency virus, anal human papillomavirus, heterosexual men, women, anal cancer

  4. Effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Feng Wen

    2017-07-01

    Full Text Available Objective: To explore effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase (MMPs, vascular esandothelial growth factor (VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer. Method: A total of 86 cases of non-squamous non-small cell lung cancer patients were divided into control group (n=44 and observation group (n=42, control group was given docetaxel combined cisplatinum chemotherapy, pemetrexed combined cis-platinum chemotherapy, was applied for observation group. Compared MMP-2, MMP-9, VEGF, NK cells and immune function level before and after treatment in both groups. Results: MMP-2, MMP-9, VEGF, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups before treatment was no significant difference. After treatment, MMP-2, MMP-9, VEGF, CD8+level in both groups was significant lower than before treatment intra-group, and observation was lower than control group, there was significant difference. After treatment, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups was increased dramatically than before treatment of intra-group, moreover, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+level in observation group after treatment was obvious higher than in control group after treatment, there was significant difference. Conclusion: Pemetrexed combined with cis-platinum chemotherapy for non-squamous non-small cell lung cancer could effectively decrease serum MMPs, VEGF level and increase NK cell level, regulate immune function, with definite clinical significance.

  5. Racial disparities in cancer-related survival in patients with squamous cell carcinoma of the esophagus in the US between 1973 and 2013.

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    Alice Kim

    Full Text Available Esophageal cancer makes up approximately 1% of all diagnosed cancers in the US. There is a persistent disparity in incidence and cancer-related mortality rates among different races for esophageal squamous cell carcinoma (SCC. Most previous studies investigated racial disparities between black and white patients, occasionally examining disparities for Hispanic patients. Studies including Asians/Pacific Islanders (API as a subgroup are rare. Our objective was to determine whether there is an association between race and cancer-related survival in patients with esophageal SCC.This was a retrospective cohort study using the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER database. The SEER registry is a national database that collects information on all incident cancer cases in 13 states of the United States and covers nearly 26% of the US population Patients aged 18 and over of White, Black, or Asian/Pacific Islander (API race with diagnosed esophageal SCC from 1973 to 2013 were included (n = 13,857. To examine overall survival, Kaplan-Meier curves were estimated for each race and the log-rank test was used to compare survival distributions. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios with 95% confidence intervals. The final adjusted model controlled for sex, marital status, age at diagnosis, decade of diagnosis, ethnicity, stage at diagnosis, and form of treatment. Additional analyses stratified by decade of diagnosis were conducted to explore possible changes in survival disparities over time. After adjustment for potential confounders, black patients had a statistically significantly higher hazard ratio compared to white patients (HR 1.08; 95% confidence interval (CI 1.03-1.13. However, API patients did not show a statistically significant difference in survival compared with white patients (HR 1.00; 95% CI 0.93-1.07. Patients diagnosed between 1973 and 1979 had twice

  6. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

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    Soroush Rais-Bahrami

    2017-01-01

    Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

  7. A common cancer in an uncommon location: A case report of squamous cell carcinoma of the nipple

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    Kelly Dye

    2017-01-01

    Conclusion: The cases of SCC of the Nipple demonstrate the importance of recognizing changes of the skin even in locations not typically associated with SCC (American Cancer Society, 2015; Scotto et al., 1983; Pendse and O’Connor, 2015; Loveland-Jones et al., 2010; Brookes et al., 2005; Sofos et al., 2013; King and Kremer, 2012; Venkataseshan et al., 1994; Hosaka et al., 2011 [1–9]. We concluded with a future suggestion of investigating possible risk factors specific to SCC of the breast or nipple.

  8. One-year follow-up of single-visit approach to cervical cancer prevention based on visual inspection with acetic acid wash and immediate cryotherapy in rural Thailand.

    Science.gov (United States)

    Chumworathayi, B; Srisupundit, S; Lumbiganon, P; Limpaphayom, K K

    2008-01-01

    The aim is to evaluate 1) the visibility of cervical squamocolumnar junction (SCJ) after cryotherapy treatment and 2) to evaluate the effectiveness of cryotherapy treatment originally performed as part of a safety, acceptability, and feasibility (SAFE) demonstration project evaluating the SAFE of visual inspection with acetic acid (VIA) followed by immediate offer of cryotherapy among those who were tested positive and eligible for treatment. A total of 704 women presented at 1-year follow-up exam during which VIA was performed again by nurses. Six hundred and forty eight (92.0%) women received colposcopy and any kind of biopsy, if indicated, by trained physician colposcopists at a referral hospital. At 1 year, VIA nurses assessed 42 of 648 referred women (6.5%) as abnormal (test positive or suspected cancer). The SCJ was visible to the colposcopists in 91.7% (594/648) of the women. Among 42 women assessed as abnormal by the nurses, colposcopic findings were abnormal in 83.3% (35/42), with one low-grade squamous intraepithelial lesion, two high-grade squamous intraepithelial lesion (HSIL), and one adenocarcinoma confirmed later by biopsy. Among 606 VIA negative women, colposcopy was abnormal in only 23.4% (142/606), with two cases of HSIL confirmed later. Given that the SCJ was visible in the vast majority of women (91.7%) after cryotherapy, VIA could be used to provide follow-up for women previously treated. The disease negative rate after cryotherapy (no human papillomavirus infection, no cervical intraepithelial neoplasia, and no cancer) at 1 year after treatment was 85.5% (554/648).

  9. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    2017-11-15

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  10. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions

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    G Kir

    2012-01-01

    Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

  11. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions

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    Patrícia Napoli Belfort-Mattos

    2016-01-01

    Full Text Available VEGF and podoplanin (PDPN have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone and podoplanin (D2-40 clone. Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P<0.001. Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P=0.016. We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P=0.018. Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression.

  12. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

    International Nuclear Information System (INIS)

    Tishler, Roy B.; Posner, Marshall R.; Norris, Charles M.; Mahadevan, Anand; Sullivan, Christopher; Goguen, Laura; Wirth, Lori J.; Costello, Rosemary; Case, MaryAnn; Stowell, Sara; Sammartino, Dan; Busse, Paul M.; Haddad, Robert I.

    2006-01-01

    Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M 2 and 25 mg/M 2 . Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to induction

  13. DNA-Cytometry of Progressive and Regressive Cervical Intraepithelial Neoplasia

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    Antonius G. J. M. Hanselaar

    1998-01-01

    Full Text Available A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN, who had received follow‐up by cytology only. Automated image cytometry of Feulgen‐stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group. The second group of 26 smears with dysplastic changes had shown regression to normal (regressive group. The goal of the study was to determine if differences in cytometric features existed between the progressive and regressive groups. CIN categories I, II and III were represented in both groups, and measurements were pooled across diagnostic categories. Images of up to 700 intermediate cells were obtained from each slide, and cells were scanned exhaustively for the detection of diagnostic cells. Discriminant function analysis was performed for both intermediate and diagnostic cells. The most significant differences between the groups were found for diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells could be classified with 60% accuracy. Cytometric features which afforded the best discrimination were characteristic of the chromatin organization in diagnostic cells (nuclear texture. Slide classification was performed by thresholding the number of cells which exhibited progression associated changes (PAC in chromatin configuration, with an accuracy of 93 and 73% for diagnostic and intermediate cells, respectively. These results indicate that regardless of the extent of nuclear atypia as reflected in the CIN category, features of chromatin organization can potentially be used to predict the malignant or progressive potential of CIN lesions.

  14. Technical challenges of sparing infrahyoid swallowing organs at risk in oropharynx squamous cell cancer treated with IMRT

    International Nuclear Information System (INIS)

    Morley, Lyndon; Tsang, Shirley W.S.; Breen, Stephen L.; Waldron, John N.; Maganti, Manjula; Pintilie, Melania; Dawson, Laura A.; Ringash, Jolie; Huang, Shao Hui; Kim, John

    2014-01-01

    This study reports clinical performance in the sparing of infrahyoid swallowing organs at risk (SWOARs) in oropharynx cancer intensity-modulated radiation therapy (IMRT) plans. Rates of meeting dose-volume planning goals are reported and compared with geometry-based estimates of what is achievable. This study also develops 3 measures of target-SWOAR geometry and tests their usefulness in providing geometry-based dose-volume planning goals. A total of 50 oropharynx cancer IMRT plans were reviewed. Success rates in meeting institutional dose-volume goals were determined for the glottic larynx (G), postcricoid pharynx (P), and esophagus (E). The following 3 measures of target-SWOAR geometry were investigated as methods of identifying geometry-based planning goals: presence of gross disease in neck levels 3 to 4, target-SWOAR overlap, and a 3-dimensional (3D) measure of target-SWOAR geometry. Locally advanced disease was predominant in this patient population with target volumes overlapping SWOARs in 68% to 98% of cases. Clinical rates of success in meeting dose-volume goals varied by SWOAR (16% to 82%) but compared well with estimated potentially achievable rates in most cases (14% average difference between clinical and potential). Cases grouped by the presence of levels 3 to 4 neck nodes or target-SWOAR overlap did not have significantly different SWOAR doses. Cases grouped using a 3D measure of target-SWOAR geometry differed significantly, providing useful geometry-based planning goals (e.g., mean Glottis dose <45 Gy was achieved 19%, 44%, or 81% of the time in each of 3 groups). This study describes the technical challenge of sparing SWOARs and investigates several potential methods for grouping cases to assist with treatment plan evaluation. Quantifying the 3-D relationship between the targets and SWOARs is a promising way of approaching this complex problem. Data presented in this paper may be useful to evaluate treatment plans using objective geometry

  15. The Analysis of Genetic Polymorphism. The Relationship between Interleukin – 4 Polymorphisms and Intraepithelial Cervical Neoplasia

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    Florin STAMATIAN

    2010-09-01

    Full Text Available Objectives: Interleukin 4 plays a critical role in T helper 2 responses to HPV infection and angiogenesis. The present study aim to study the association between the IL4 promoter polymorphism – 590 C>T, respectively VNTR intron 2 polymorphism and cervical intraepithelial neoplasia. Material and method: We have realized a prospective case controls study that included 128 cases of intraepithelial neoplasia positive for HPV HR testing and 111 controls negative for intraepithelial lesion and also negative for HPV HR. Clinical examination was performed on each patient; blood and cervical sample were obtained. Cervical probes were analyzed regarding cytology and HPV HR testing. From peripheral blood DNA sample was obtain followed by genotype analysis for IL4 -590 C>T using PCR RFLP, respectively IL4 70 bp VNTR determined by PCR. Results: The absolute frequency of genotypes for IL4 -590 C>T was T/T-5, C/T-42, C/C-81 in the cases group respectively T/T-2, C/T-32, C/C-77 in the control group. The chi-square test had a value of 0.983 (p=0.321 while considering the presence of a minimum one single variant allele as a risk factor for cervical cancer, respectively 0.926 (p=0.336 for homozygous variant genotype. Odds ratio was 0.761 (95%CI [0.443-1.306] while considering C/T+T/T respectively 2R/3R, 2R/2R as a risk factor, and 0.451 (95%CI 95% [0.086-2.374] - TT respectively 2R/2R as a risk factor. Conclusion: No linear statistical significant association has been found between IL4 polymorphism and cervical neoplasia (p = 0.322.

  16. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

    Directory of Open Access Journals (Sweden)

    Joshua D. Campbell

    2018-04-01

    Full Text Available Summary: This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs from five sites associated with smoking and/or human papillomavirus (HPV. SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs, DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+ and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches. : Campbell et al. reveal that squamous cell cancers from different tissue sites may be distinguished from other cancers and subclassified molecularly by recurrent alterations in chromosomes, DNA methylation, messenger and microRNA expression, or by mutations. These affect squamous cell pathways and programs that provide candidates for therapy. Keywords: genomics, transcriptomics, proteomics, head and neck squamous cell carcinoma, lung squamous cell carcinoma, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, bladder carcinoma with squamous differentiation, human papillomavirus

  17. Cervical cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) in four US-Affiliated Pacific Islands between 2007 and 2015.

    Science.gov (United States)

    Senkomago, Virginia; Royalty, Janet; Miller, Jacqueline W; Buenconsejo-Lum, Lee E; Benard, Vicki B; Saraiya, Mona

    2017-10-01

    Cervical cancer incidence in the US-Affiliated Pacific Islands (USAPIs) is double that of the US mainland. American Samoa, Commonwealth of Northern Mariana Islands (CNMI), Guam and the Republic of Palau receive funding from the Centers for Disease Control (CDC) National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to implement cervical cancer screening to low-income, uninsured or under insured women. The USAPI grantees report data on screening and follow-up activities to the CDC. We examined cervical cancer screening and follow-up data from the NBCCEDP programs in the four USAPIs from 2007 to 2015. We summarized screening done by Papanicolaou (Pap) and oncogenic human papillomavirus (HPV) tests, follow-up and diagnostic tests provided, and histology results observed. A total of 22,249 Pap tests were conducted in 14,206 women in the four USAPIs programs from 2007-2015. The overall percentages of abnormal Pap results (low-grade squamous intraepithelial lesions or worse) was 2.4% for first program screens and 1.8% for subsequent program screens. Histology results showed a high proportion of cervical intraepithelial neoplasia grade 2 or worse (57%) among women with precancers and cancers. Roughly one-third (32%) of Pap test results warranting follow-up had no data recorded on diagnostic tests or follow-up done. This is the first report of cervical cancer screening and outcomes of women served in the USAPI through the NBCCEDP with similar results for abnormal Pap tests, but higher proportion of precancers and cancers, when compared to national NBCCEDP data. The USAPI face significant challenges in implementing cervical cancer screening, particularly in providing and recording data on diagnostic tests and follow-up. The screening programs in the USAPI should further examine specific barriers to follow-up of women with abnormal Pap results and possible solutions to address them. Published by Elsevier Ltd.

  18. NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Ma, Yue; Kong, Jienan; Yan, Guanghai; Ren, Xiangshan; Jin, Dan; Jin, Tiefeng; Lin, Lijuan; Lin, Zhenhua

    2014-01-01

    NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome 16q22, functions primarily to protect normal cells from oxidant stress and electrophilic attack. Recent studies have revealed that NQO1 is expressed at a high level in most human solid tumors including those of the colon, breast, pancreas, ovaries and thyroid, and it has also been detected following the induction of cell cycle progression and proliferation of melanoma cells. In this study, we aimed to investigate the clinicopathological significance of upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the uterine cervix. The localization of the NQO1 protein was determined in the SiHa cervical squamous cancer cell line using immunofluorescence (IF) staining, and immunohistochemical (IHC) staining performed on paraffin-embedded cervical SCC specimens from 177 patients. For comparison, 94 cervical intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1 mRNA expression levels, and HPV infection status was genotyped using oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall survival (OS) rates for all cervical SCC patients were calculated using the Kaplan–Meier method, and univariate and multivariate analysis was performed using the Cox proportional hazards regression model. The NQO1 protein showed a mainly cytoplasmic staining pattern in cervical cancer cells, and only three cases of cervical SCC showed a nuclear staining pattern. The strongly positive rate of NQO1 protein expression was significantly higher in cervical SCCs and CINs than in normal cervical epithelia. High-level NQO1 expression was closely associated with poor differentiation, late-stage, lymph node metastasis and high-risk for HPV infection. Additionally, high-level NQO1 expression was associated with lower DFS and 5-year OS rates, particularly for patients with early-stage cervical SCCs

  19. Human papillomavirus infection among Bangladeshi women with cervical intraepithelial neoplasia and chronic cervicitis

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    Elisha Khandker

    2016-01-01

    Full Text Available Background and objectives: Cervical cancer is one of the leading causes of morbidity and mortality. Human papillomavirus (HPV is known to be associated with cervical intraepithelial neoplasia (CIN and cancer. The objective of the present study was to determine the rate of HPV infection among the Bangladeshi women with different grades of CIN and cancer. Methods: Women aged 20 to 55 years, diagnosed as a case of chronic cervicits, cervical intraepithelial neoplasia (CIN or invasive cancer by Papanicolaou (Pap smear and colposcopy directed biopsy were enrolled in the study. High and intermediate risk oncogenic HPV were detected in cervical samples by real time PCR (rt-PCR. Results: Seventy two women with chronic cervicitis and different grades of CIN were included in the study. Out of 72 cases, 28 (38.9% and 44 (61.1% had chronic cervicitis and CIN respectively. Overall, the HPV infection rate was 43.1% (95% CI= 32%-54% among the study population. CIN cases had significantly high (p<0.01 HPV infection (78.6%; 95% CI=60%-89% compared to cases with chronic cervicitis (18.2%; 95% CI=11.1%-34.5%. Women between the age of 20-30 years had the highest positive rate (50.0% followed by 31-40 years age group (43.6%. All CIN grade 2 and 3 had HPV infection. Conclusion: The study showed that HPV was strongly associated with different grades of CIN. Specific HPV types should be determined to find out the most prevalent HPV types among the Bangladeshi women with CIN and cervical cancers. IMC J Med Sci 2016; 10(1: 29-32

  20. Tratamento endoscópico do câncer epidermóide do esôfago Endoscopic treatment of squamous cell esophageal cancer

    Directory of Open Access Journals (Sweden)

    Fauze Maluf-Filho

    2006-06-01

    esophageal cancer. DATA SOURCE: Relevant publications cited at PubMed database in the last 10 years were analyzed and compared with the experience developed at the Gastrointestinal Endoscopy Division of the Department of Gastroenterology of the University of São Paulo School of Medicine. Mucosectomy and advanced tumor tunnelization were the most important developments in that area. DATA SYNTHESIS: Endoscopic mucosal resection of early epidermoid cancer of the esophagus is indicated when the lesion is confined to the epithelium (m1 or to the lamina propria (m2. The described 5-year survival rate after endoscopic mucosal resection of intramucosal epidermoid tumor of the esophagus approaches 95%. Based on the available evidence, it seems reasonable to indicate endoscopic mucosal resection as a first-choice treatment for patients with intramucosal epidermoid esophageal carcinoma. There are a variety of endoscopic palliative methods for dysphagia relief in advanced esophageal cancer. CONCLUSIONS: The choice will vary according to the anatomical features and location of the tumor, patient preferences, local and expertise availability. The technical success rate for placement of metal stents across the malignant stenosis is close to 100%. The rate of long-term palliation of dysphagia approaches 80% which makes expandable metal stents the treatment of choice for palliation of obstructive symptoms caused by advanced squamous cell cancer of the esophagus.

  1. Adjuvant intravenous methotrexate or definitive radiotherapy alone for advanced squamous cancers of the oral cavity, oropharynx, supraglottic larynx or hypopharynx

    International Nuclear Information System (INIS)

    Fazekas, J.T.; Sommer, C.; Kramer, S.

    1980-01-01

    Three hundred twenty-six patients with advanced head and neck cancers were randomized to receive definitive radiotherapy alone while 312 similar patients first received intravenous Methotrexate. No significant bias was demonstrated between the two patient populations. The number of annual deaths among the two randomized categories was essentially equal during the first 5 years. Nearly one-half occurred in the first year (146 for radiation alone and 143 in the chemotherapy plus irradiation groups). Median metastasis-free survival was between 12 to 13 months in both categories. The unadjusted 5 year survivals were in the 11 to 22% range for oral cavity, oropharynx, and supraglottic larynx and 3 to 9% for hypopharynx primaries. Although several variables did exert an impact upon survival, primary (T) and lymph node (N) stage seem to be of paramount importance and Methotrexate of minor consideration. Median and 5-year survivals within the various anatomic regions were consistently better when Methotrexate was given. However, these improvements were minimal and depended upon whether comparisons were performed on adjusted or unadjusted survival figures. In view of the modest benefits attained by using this Methotrexate regimen the authors suggest that other adjuvant programs be investigated and that this schedule not be adopted for routine clinical usage

  2. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2018-01-12

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  3. Quality of life outcome measures using UW-QOL questionnaire v4 in early oral cancer/squamous cell cancer resections of the tongue and floor of mouth with reconstruction solely using local methods.

    Science.gov (United States)

    Boyapati, Raghuram P; Shah, Ketan C; Flood, Valerie; Stassen, Leo F A

    2013-09-01

    Cancer treatment either by surgery alone or in a combination of surgery, radiotherapy±chemotherapy has significant consequences on the physical, mental, emotional and psychosocial wellbeing of the patient. Measurement of quality of life (QOL) is necessary to understand the patient's perception of their own treatment, as clinicians' views can be biased. Reconstruction of a cancerous defect with a free vascular flap is ideal in large, often composite defects, provided it is appropriate to the advanced stage and prognosis of the disease, medical condition of the patient, availability of surgical and financial resources and allows the prosthetic rehabilitation of the anatomic area. Using University of Washington Quality of life 4 questionnaire (UW-QOL4), we assessed the QOL of 38 patients, who underwent local surgical reconstructions after resection of T1/T2 tongue/floor of mouth squamous cell carcinoma defects. Objective assessment of speech and swallow function was also carried out using therapy outcome measure (TOM) scores by the speech and language therapy team (SALT) aiming to see the differences in the scores obtained in patients who underwent post-operative radiotherapy. Our study, conducted 6months after completion of all oncologic treatment for the primary disease, showed satisfactory levels of quality of life parameters with good function showing that local reconstructive methods are successful and may have benefits in the management of early oral cancers involving the tongue and floor of mouth. They are beneficial by providing a good quality in terms of function, by reducing the operating time, the surgical morbidity, simplifying post-operative care and thereby becoming an efficient, effective and a cost effective method. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Increased burden of treatment of cervical intraepithelial neoplasia: Denmark 1991 to 2007

    DEFF Research Database (Denmark)

    Barken, Sidsel Svennekjær; Rebolj, M; Lynge, Elsebeth

    2011-01-01

    Introduction: Since the introduction of cytological screening in Denmark in the late 1960s, the incidence of cervical cancer decreased from 40 to 14 per 100,000 due to treatment of screen-detected cervical intraepithelial neoplasia (CIN). However, some overtreatment is inevitable and its side...... on conisations, destructive therapies, excisions, hysterectomies and cervical treatments NOS from: The Pathology, Hospital Discharge, Health Insurance and Danish Cancer Register, for all female Danish residents aged 15 to 84 between 1991 and 2007. After linking the data using the unique Danish identification...... numbers, we excluded all duplicates and all destructive therapies and hysterectomies for which no cervical diagnosis was found in the period around the treatment. The total number of treatments was age-standardized using the Danish female population in 2007 as the standard population. Results...

  5. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

    OpenAIRE

    Joshua D. Campbell; Christina Yau; Reanne Bowlby; Yuexin Liu; Kevin Brennan; Huihui Fan; Alison M. Taylor; Chen Wang; Vonn Walter; Rehan Akbani; Lauren Averett Byers; Chad J. Creighton; Cristian Coarfa; Juliann Shih; Andrew D. Cherniack

    2018-01-01

    Summary: This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mes...

  6. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

  7. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

    Science.gov (United States)

    Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

    2007-01-01

    Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH

  8. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

    Directory of Open Access Journals (Sweden)

    Dandash Khadiga

    2007-07-01

    Full Text Available Abstract Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx, a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap smears were evaluated using the Bethesda system (TBS, followed by colposcopic guided biopsy (CGB for all epithelial abnormalities (EA. In a third step, HPV was tested on all EA by in-situ hybridization (ISH using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2, cytomegalovirus (CMV, and human immunodeficiency virus (HIV. Results EA representing 7.8% (424/5453, were categorized into atypical squamous cell of undetermined significance (ASCUS (34.4%, atypical glandular cell of undetermined significance (AGCUS (15.3%, combined ASCUS and AGCUS (3.1%, low grade squamous intraepithelial lesions (SIL (41.0%, high grade SIL (5.2% and invasive lesions (1%. CGB of EA (n = 281 showed non neoplastic lesions (12.8%, atypical squamous metaplasia (ASM (19.2%, cervical intraepithelial neoplasia I (CIN (44.4%, CIN II (4.4%, CINIII (2.8%, endocervical lesions (5.2%, combined squamous and endocervical lesions (10.0%, invasive squamous cell carcinoma (SCC (0.02% and extranodal marginal zone B cell lymphoma (MZBCL (0.02%. The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed

  9. Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT.

    Science.gov (United States)

    Dell'Acqua, V; Kobiela, J; Kraja, F; Leonardi, M C; Surgo, A; Zerella, M A; Arculeo, S; Fodor, C; Ricotti, R; Zampino, M G; Ravenda, S; Spinoglio, G; Biffi, R; Bazani, A; Luraschi, R; Vigorito, S; Spychalski, P; Orecchia, R; Glynne-Jones, R; Jereczek-Fossa, B A

    2018-03-28

    Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients' data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6-78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ 2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution-particularly in females with involvement of the vagina or the vaginal septum.

  10. RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck

    International Nuclear Information System (INIS)

    Spencer, S.A.; Harris, J.; Wheeler, R.H.; Machtay, M.; Schultz, C.; Spanos, W.; Rotman, M.; Meredith, R.

    2001-01-01

    Purpose: Patients with recurrent squamous cell cancer of the head and neck (SCH and N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. Methods and Materials: The eligibility requirements included SCH and N presenting as a second primary or recurrence ≥6 months after definitive RT to ≥45 Gy, with ≥75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by ≥6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m 2 of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. Results: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p=0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p=0.083). Conclusion: Repeated RT with concurrent chemotherapy as

  11. Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck

    International Nuclear Information System (INIS)

    Fazekas, J.; Pajak, T.F.; Wasserman, T.; Marcial, V.; Davis, L.; Kramer, S.; Rotman, M.; Stetz, J.

    1987-01-01

    As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to standard 5 treatments per week among control patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for control patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial

  12. Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

    Science.gov (United States)

    Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

    2015-01-01

    In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

  13. Characteristic cytokine generation patterns in cancer cells and infiltrating lymphocytes in oral squamous cell carcinomas and the influence of chemoradiation combined with immunotherapy on these patterns.

    Science.gov (United States)

    Yamamoto, Tetsuya; Kimura, Tsuyoshi; Ueta, Eisaku; Tatemoto, Yukihiro; Osaki, Tokio

    2003-01-01

    Cytokines produced by tumor cells and tumor-infiltrating lymphocytes (TIL) appear to regulate tumor cell growth and the cytotoxic activity of TIL. The objectives of the present study were to investigate cytokine generation patterns in tumor cells and TIL and to examine the influence of cancer therapy on this cytokine production and the cytotoxic activity of TIL. We determined the levels of cytokines produced by tumor cells and TIL in vitro and measured the cytotoxic activity of TIL against Daudi cells in patients with oral squamous cell carcinoma (OSC) before and 1 week after the start of concomitant chemo-radio-immunotherapy. Before the therapy, OSC cells generated higher levels of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) than did oral keratinocytes isolated from the noninflamed gingivae of healthy individuals, but both kinds of cells generated similar levels of interleukin (IL)-1beta and IL-6. Compared with peripheral blood mononuclear cells (PBMC) of the patients, TIL produced higher levels of IL-1beta, IL-6, IL-10, TNF-alpha and TGF-beta, whereas their production of IL-12 and interferon-gamma (IFN-gamma) was only slightly higher than that in PBMC. After 1 week of therapy, the cytokine production by OSC cells had largely decreased, while the production of TNF-alpha, IFN-gamma, TGF-beta and IL-12 by TIL had increased greatly, although other cytokine levels were almost constant during the investigations. The cytotoxic activity of TIL was higher than that of PBMC before the therapy, and this activity was strongly increased by 1 week of therapy. These results suggest that the cytokine productivities of TIL and tumor cells differ from those of PBMC and normal keratinocytes, respectively, and that chemo-radio-immunotherapy modulates in situ cytokine generation, which is advantageous for inhibition of tumor cell growth and activation of TIL. Copyright 2003 S. Karger AG

  14. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  15. Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

    Science.gov (United States)

    Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

    2017-05-01

    This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

  16. IMPACT STUDY: MK-0646 (DALOTUZUMAB, INSULIN GROWTH FACTOR 1 RECEPTOR (IGF-1R ANTIBODY COMBINED WITH PEMETREXED AND CISPLATIN IN STAGE IV METASTATIC NON-SQUAMOUS LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Chao H Huang

    2016-01-01

    Full Text Available Background: Insulin-like growth factor 1 receptor (IGF-1R regulates cell growth, proliferation and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D is a humanized monoclonal antibody that targets IGF-1R. Pemetrexed (P has higher activity in non-squamous lung cancer (NSQL. We initiated a randomized phase II trial to test the combination of P and Cisplatin (C +/- D in NSQL.Methods: Eligibility criteria: untreated NSQL stage IIIB or IV, ECOG 0 or 1, measurable disease, adequate renal, hepatic and hematologic function, and no other intercurrent illness. P at 500mg/m2 and C at 75mg/m2 IV were given every 3 weeks. D was given at 10mg/kg IV weekly on days 1, 8 and 15 of every 3-week cycle in the experimental group. The patients had a radiographic assessment after every 2 cycles and were treated for a maximum of 6 cycles if there was a response or stable disease. The primary objective of the study was to compare the clinical response rates of PC vs PC+D. Results: From 1/2009 to 2/2011, the study accrued 26 subjects: 16 male and 10 female, with a median age of 59; 14 were treated with PC and 12 were treated with PC+D. We observed 2 partial responses (PR, 7 stable disease (SD, 3 progressive disease (PD, and 2 were not evaluable (NE in the PC arm. In comparison, for the PC+D arm there were: 3 PR, 4 SD, 4 PD and 1 NE. The hematologic toxicity was similar in both groups. There higher incidence of hyperglycemia the experimental group; 4 cases with grade 3 and 1 case with grade 4. Conclusion: PC+D had a similar response rate compared to PC, with a higher rate of hyperglycemia. Identification of responders using predictive markers would be key to continuing the study of D in NSQL.

  17. Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High-Dose Rate Brachytherapy (PHDRB)

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Monge, Rafael, E-mail: rmartinezm@unav.es [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Pagola Divasson, Maria; Cambeiro, Mauricio; Gaztanaga, Miren; Moreno, Marta; Arbea, Leire [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Montesdeoca, Nestor [Department of Maxillofacial Surgery, Clinica Universitaria de Navarra, Pamplona (Spain); Alcalde, Juan [Department of Otolaryngology, Clinica Universitaria de Navarra, Pamplona (Spain)

    2011-11-15

    Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade {>=}4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade {>=}3 and {>=}4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV{sub 150} values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

  18. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Ana Cristina Macêdo Barcelos

    2011-01-01

    Full Text Available Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL, or high-grade squamous intraepithelial lesion (HSIL. If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%, being 38 (54.2% reactive ASCUS and 32 (45.71% neoplastic ASCUS; 62 (88.5% ASC-US and 8 (11.41% ASC-H. ASCUS (Regione Protocol, respectively 1-5: 15 (21.4%, 19 (27.1%, 3 (27.1%, 16 (22.8%, and 1 (1.4%. A higher number of cases of cervical intraepithelial neoplasia (CIN II/III in the biopsies of patients with ASC-H compared to ASC-US (P=.0021. High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P=.031. Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

  19. Prevalence of intraepithelial lesion in cervical screening cytology in a First-level Care Unit

    Science.gov (United States)

    Solís, José Gabriel; Briones-Torres, Tomás Iván

    2018-01-01

    Cervical cancer represents the second leading cause of malignant neoplasm mortality in women globally. Cervical cytology is the most important screening study. It is therefore of interest to know the prevalence of cytological alterations in the Mexican population. In this study the objective was to calculate the prevalence of intraepithelial lesion in cervical screening cytology. An observational, descriptive and cross-sectional study was developed; the sample was 379 patients from 21 to 64 years of age; we included patients who underwent cervical screening cytology registered in the Detección Oportuna de Cáncer Cervicouterino (DOC-CACU) program database. A descriptive analysis of the data was performed. A prevalence of intraepithelial lesion of 4.49% was found. The 3.17% corresponded to LIEBG and 1.32% to LIEAG. No reports of invasive carcinoma were found. Of these patients, 64.71% corresponded to the age group from 41 to 60 years. 52.94% had had their last cytology in the previous 3 years or more and 35.29% were in postmenopause. A prevalence consistent with what was described in the literature was found. More than half of the affected patients had their last cytology in the previous 3 or more years and corresponded to the age group from 41 to 60 years. A high proportion of patients were in postmenopause.

  20. HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Oscar Peralta-Zaragoza

    2013-01-01

    Full Text Available Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

  1. Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

    Science.gov (United States)

    Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W

    2016-06-01

    Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

  2. Cold-knife and laser conization for cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Tabor, A; Berget, A

    1990-01-01

    In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice...

  3. Serous tubal intraepithelial neoplasia : The concept and its application

    NARCIS (Netherlands)

    Meserve, Emily E. K.; Brouwer, Jan; Crum, Christopher P.

    In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that

  4. EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa.

    Science.gov (United States)

    Bogaert, Lies; Willemsen, Anouk; Vanderstraeten, Eva; Bracho, Maria A; De Baere, Cindy; Bravo, Ignacio G; Martens, Ann

    2012-07-06

    Squamous cell carcinoma (SCC) represents the most common genital malignant tumor in horses. Similar to humans, papillomaviruses (PVs) have been proposed as etiological agents and recently Equine papillomavirus type 2 (EcPV2) has been identified in a subset of genital SCCs. The goals of this study were (1) to determine the prevalence of EcPV2 DNA in tissue samples from equine genital SCCs, penile intraepithelial neoplasia (PIN) and penile papillomas, using EcPV2-specific PCR, (2) to examine the prevalence of latent EcPV2 infection in healthy genital mucosa and (3) to determine genetic variability within EcPV2 and to disentangle phylogenetic relationships of EcPV2 among PVs. EcPV2 DNA was detected in all but one penile SCC (15/16), in all PIN lesions (8/8) and penile papillomas (4/4). Additionally, EcPV2 DNA was demonstrated in one of two metastasized lymph nodes, one contact metastasis in the mouth, two vaginal and one anal lesion. In healthy horses, EcPV2 DNA was detected in 10% (4/39) of penile swabs but in none of vulvovaginal swabs (0/20). This study confirms the presence of EcPV2 DNA in equine genital SCCs and shows its involvement in anal lesions, a lymph node and contact metastases. Latent EcPV2 presence was also shown in normal male genital mucosa. We found that different EcPV2 variants cocirculate among horses and that EcPV2 is related to the Delta+Zeta PVs and is only a very distant relative of high-risk human PVs causing genital cancer. Thus, similar viral tropism and similar malignant outcome of the infection do not imply close evolutionary relationship. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Unmet needs in squamous cell carcinoma of the lung: potential role for immunotherapy.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-05-01

    Squamous cell carcinoma of the lung accounts for 20-30% of non-small cell lung cancers (NSCLC). Despite the differences in disease characteristics between squamous and non-squamous NSCLC, both have historically been treated similarly in the clinic. Recently approved drugs have revealed differences in activity and safety profiles across histologic subtypes and have applicability in treating non-squamous, but not typically squamous, NSCLC. Exploration of immune checkpoints--co-inhibitory molecules used to regulate immune responses--has resulted in novel immunotherapies designed to interrupt signaling through the cytotoxic T lymphocyte-associated antigen-4 or programmed cell death protein-1 pathways on lymphocytes. Modulation of these pathways can lead to restored antitumor immune responses, and preliminary evidence shows that agents targeting these pathways have activity in lung cancer, including squamous NSCLC.

  6. Neoplasia intra-epitelial grau III da vulva e da região perianal tratada com vulvectomia superficial: relato de caso High-grade vulvar and perianal intraepithelial neoplasia treated with skinning vulvectomy: a case report

    Directory of Open Access Journals (Sweden)

    Walquíria Quida Salles Pereira Primo

    2003-05-01

    Full Text Available A neoplasia intra-epitelial vulvar grau III (NIV III se manifesta de modo visível, portanto, acessível à biópsia e, por conseguinte, ao diagnóstico histológico. Há duas formas precursoras do câncer vulvar: a NIV associada ao papiloma vírus humano (HPV e a NIV associada ao líquen simples crônico, hiperplasia de células escamosas e líquen escleroso, não tratados. Porém, pode existir sobreposição das duas formas. O termo papulose bowenóide, apesar de ser desencorajado, define uma das formas clínicas da NIV, que se apresenta como lesões pigmentadas, verruciformes, papulares e múltiplas. A NIV III está associada com HPV em mais de 80% dos casos e em 40% das vezes, nota-se envolvimento perianal. O seu tratamento é muito difícil e pode ocorrer recorrência em qualquer tempo e por muitos anos. Embora não exista tratamento padrão definido, os trabalhos apontam para a cirurgia, respeitando margem de segurança, como o mais adequado.High-grade vulvar intraepithelial neoplasia (VIN III is a visible lesion; therefore, it is accessible to biopsy and thus, to a histological diagnosis. There are two forms of vulvar cancer precursors: VIN caused by human papillomavirus (HPV and VIN associated with untreated lichen simplex chronicus, squamous cell hyperplasia, and lichen sclerosus. There may be overlap of the two forms. The term bowenoid papulosis, although discouraged, identifics a clinical form of VIN III. Such lesion appears as pigmented, wart-like growths or papules. VIN III is associated with HPV in more than 80% of the cases, and ther