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Sample records for cervical squamous intraepithelial

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

    African Journals Online (AJOL)

    Abstract: Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in Tanzanian women. Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming ...

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

    African Journals Online (AJOL)

    AJRH Managing Editor

    Cervical cancer is the second most common cancer among women worldwide. Infection with the human immunodeficiency virus. (HIV) and its related immunosuppression are associated with an increased risk of prevalent, incident, and persistent squamous intraepithelial lesions (SILs) of the cervix. The objective of the study ...

  3. Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion

    OpenAIRE

    Santos,André Luis Ferreira; Derchain,Sophie Françoise Mauricette; Martins,Marcos Roberto; Sarian,Luís Otávio Zanatta; Martinez,Edson Zangiacome; Syrjänen,Kari Juhani

    2003-01-01

    CONTEXT: Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE: To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF S...

  4. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

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    Vallejo-Ruiz Verónica

    2010-11-01

    Full Text Available Abstract Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL. These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation.

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

    OpenAIRE

    Veiga, Fernanda Rangel da; Russomano, Fábio Bastos; Camargo, Maria José de; Monteiro, Aparecida Cristina Sampaio; Tristão, Aparecida; Silva, Gabriela Villar e

    2009-01-01

    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 unsa...

  6. 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

  7. CCNA1 promoter methylation: a potential marker for grading Papanicolaou smear cervical squamous intraepithelial lesions.

    Science.gov (United States)

    Chujan, Suthipong; Kitkumthorn, Nakarin; Siriangkul, Sumalee; Mutirangura, Apiwat

    2014-01-01

    From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low- grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

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

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    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

  9. 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.

  10. Perbedaan Ekspresi P16INK4a dan HPVL1 pada Cervical Intraepithelial Neoplasia 1, Cervical Intraepithelial Neoplasia 2, Cervical Intraepithelial Neoplasia 3 dan Squamous Cell Carcinoma Serviks Uteri

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    Arlene Elizabeth Padang

    2014-09-01

    Full Text Available Human papillomavirus (HPV memegang peranan penting dalam proses karsinogenesis kanker serviksuteri; namun hanya sebagian kecil wanita yang terinfeksi tersebut akan berkembang menjadi kankerserviks yang invasif. Cervical intraepithelial neoplasia (CIN merupakan spektrum dari lesi servikalyang mewakili lesi prekursor dari squamous cell carcinoma (SCC serviks uteri yang dikategorikanmenjadi CIN1, CIN2, CIN3. Interaksi protein HPV (E6 dan E7 dengan protein pengatur selular (pRbdan p53 akan menyebabkan up regulation protein P16INK4a. P16INK4a merupakan tumor supresorprotein cyclin dependen kinase inhibitor yang menghambat cyclin dependent kinase 4 dan 6 yangmerupakan produk dari gen INK4a yang terlibat dalam fosforilasi protein retinoblastoma (pRb.Human papillomavirus-late 1 (HPVL1 merupakan protein kapsid yang terekspresi pada saat awalfase produktif karsinogenesis serviks uteri. Tujuan dari penelitian ini adalah untuk mengetahuiperbedaan ekspresi protein P16INK4a dan HPVL1 pada CIN1, CIN2, CIN3, dan SCC serviks uteri,dimana ekspresi P16INK4a dapat membantu untuk membedakan berbagai derajat displasia serviksuteri dan ekspresi HPVL1 dapat membantu untuk memprediksi progresivitas dari berbagai derajatdisplasia serviks uteri, sehingga penanganan pasien menjadi lebih tepat. [MEDICINA 2013;44:77-81].

  11. Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes.

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    Sherman, Mark E; Castle, Philip E; Solomon, Diane

    2006-10-25

    The 2001 Bethesda System category of atypical squamous cells (ASC) denotes changes suggestive, but inconclusive for, a squamous intraepithelial lesion (SIL). ASC is subcategorized as: 1) "undetermined significance (ASC-US)," when changes suggest low-grade or indeterminate-grade SIL and 2) "cannot exclude high-grade squamous intraepithelial lesion (ASC-H)," when a cancer precursor is suspected. To better define the characteristics of ASC-H, the authors analyzed and compared human papillomavirus (HPV) testing data and outcomes after 2 years for participants in the Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS), a randomized trial of 5060 women. Among women with thin-layer cytology findings of ASC-H, 84% tested positive for HPV, 50% (95% confidence interval [95% CI], 41%-60%) were diagnosed with cervical intraepithelial neoplasia (CIN) type 2+, and 30% (95% CI, 22-39%) were diagnosed with CIN3+. Positive HPV tests and diagnoses of CIN2+ and CIN3+ were found to be more common among women with ASCH compared with those with ASC-US, but the highest frequencies were found to be associated with high-grade SIL. For women age /=35 years tested positive for HPV (P = 0.009). A finding of ASC-H seems to confer a substantially higher risk for CIN2+ and CIN3+ than ASC-US. Immediate colposcopy may be the appropriate management for young women with ASC-H, but the utility of HPV testing for managing older women with ASC-H requires additional study. (c) 2006 American Cancer Society.

  12. 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.

  13. Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

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    Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

    2015-09-01

    Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  14. Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin by conization: a retrospective analysis.

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    Dou, Yuya; Zhang, Xiaodan; Li, Yang; Wang, Fenfen; Xie, Xing; Wang, Xinyu

    2017-06-01

    The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion (HSIL) patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 (47.06%) patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma (3 stage IA1 and 1 stage IA2 patients). Univariate analysis showed that patient age > 35 years (P = 0.005), menopausal period > 5 years (P = 0.0035), and multiple-quadrant involvement (P = 0.001) were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement (P = 0.001; OR, 3.701; 95%CI, 1.496-9.154) was an independent risk factor for residual disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider reconization or re-assessment.

  15. Usefulness of p16(INK4a) staining for managing histological high-grade squamous intraepithelial cervical lesions.

    Science.gov (United States)

    Miralpeix, Ester; Genovés, Jordi; Maria Solé-Sedeño, Josep; Mancebo, Gemma; Lloveras, Belen; Bellosillo, Beatriz; Alameda, Francesc; Carreras, Ramon

    2017-02-01

    p16(INK4a) (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining. Patients diagnosed with HSIL/CIN2 colposcopy-directed biopsy, were recruited prospectively between December 2011 and October 2013. p16 staining was performed in all HSIL/CIN2 diagnostic biopsies. Follow-up was conducted every 4 months by cytology, colposcopy and biopsy if suspicion of progression and once the 12 months of follow-up completed. Complete regression, partial regression, persistence, and progression rates of HSIL/CIN2 were defined as a final outcome. A total of 96 patients were included in the analysis. The rate of spontaneous regression was 64%, while 28% had persistent disease, and 8% progressed at 12 months of follow-up. p16 was positive in 81 (84%) initial HSIL/CIN2 biopsies. Regression was observed in all 15 p16 negative cases and in 46 of 81 (57%) p16 positive cases (P=0.001). In conclusion, patients with p16 negative HSIL/CIN2 biopsy had a high rate of regression during first 12 months of follow-up. Status of p16 staining could be considered for HSIL/CIN2 management.

  16. Papanicolau smear chances to be diagnostic for cervical squamous intraepithelial lesions (SIL) with or without detectable HPV DNA at in situ hybridization analysis.

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    Sopracordevole, F; Cadorin, L; Muffato, G; De Benetti, L; Parin, A

    1993-01-01

    The Authors have correlated 39 cervical diagnostic biopsies for squamous intraepithelial lesions (SILs) with correspective Papanicolau smears (PS), with relation to the presence or the absence of HPV of oncogenic type (HPV-one) detected by in situ hybridization (ISH). Agreement between cytological and histological diagnosis was present in 14 of 16 cases with detectable HPV-one and only in 12 of 23 cases without detectable HPV-one at ISH. The importance of the HPV type in the SILs with relation to the diagnostic accuracy of Papanicolaou smears has been discussed.

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

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    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.

  18. IMMUNOHISTOCHEMICAL ASSESSMENT OF P16 PROTEIN AND OF L1 CAPSID PROTEIN OF HUMAN PAPILLOMA VIRUS IN CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS

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    Eduard Crauciuc

    2012-06-01

    Full Text Available The purpose of this study was to accomplish a comparative assessment between the immunohistochemical and immunocytochemical expression of p16 protein and of L1capsid protein respectively of HPV, high grade and low grade squamous intraepithelial lesion, in order to determine, by morph-clinical  correlations, their practical applicability in diagnosing and the subsequent monitoring of the patients. For the cases studied, HPV L1 capsid protein was present in 66.7% of LSIL, 17.6% of HSIL and 18.2% of ASCUS. From all cervical biopsies, p16 biomarker was positive for 54.8% of LSIL, 98% of HSIL and 45.5% of ASCUS. The biggest part of cervical cancer cases are caused by HPV virus infection. HPV vaccine protects against 4 HPV roots that cause about 70% of cervical cancer cases.

  19. 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.

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

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    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.

  1. Clinical significance of CK7, HPV-L1, and koilocytosis for patients with cervical low-grade squamous intraepithelial lesions: a retrospective analysis.

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    Cao, Lanqing; Sun, Ping-Li; Yao, Min; Chen, Shifan; Gao, Hongwen

    2017-07-01

    Most cervical low-grade squamous intraepithelial lesions (LSILs) do not progress to high-grade squamous intraepithelial lesions (HSILs); however, reliable biomarkers that predict LSIL progression are lacking. We investigated the association of cytokeratin 7 (CK7), human papillomavirus-L1 capsid protein (HPV-L1), and koilocytosis with clinical outcomes of patients with LSIL. CK7, HPV-L1, Ki67, and p16-INK4A expression was determined in 72 cervical LSIL and 28 HSIL biopsy samples; koilocytosis was evaluated by reviewing biopsy slides. Fifty patients with LSIL received follow-up. CK7, HPV-L1, and koilocytosis were detected in 48.6%, 44.4%, and 52.0% of LSIL tissues and in 78.6%, 10.7%, and 64.3% of HSIL tissues, respectively. Lesion grade was correlated directly with CK7 expression (P=.007) and inversely with HPV-L1 expression (P=.004). CK7 expression in LSILs was correlated inversely with HPV-L1 expression and directly with p16-INK4A and Ki67 status. Furthermore, koilocytosis was significantly associated with HPV-L1 and p16-INK4A expression. Progression to cervical intraepithelial lesions of grades ≥2 occurred in 34% of cases. CK7 negativity and HPV-L1 positivity were significantly associated with lower HSIL progression rates. HPV-L1-positive and CK7-negative LSILs showed significantly lower progression rates compared with HPV-L1-negative and CK7-positive LSILs (6.3% v-positive cases showed a significantly lower progression rate (17.6%) compared with nonkoilocytic and HPV-L1-negative cases (50%). CK7-negative, HPV-L1-positive, and koilocytic LSILs showed a progression rate of 7.7%. Koilocytosis and p16-INK4A were not significantly associated with clinical outcomes. Hence, evaluating HPV-L1, CK7, and koilocytosis profiles combined may be more reliable for LSIL prognostication. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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.

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    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.

  3. Enhanced sialyltransferases transcription in cervical intraepithelial neoplasia.

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    López-Morales, Dolores; Velázquez-Márquez, Noé; Valenzuela, Olivia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2009-03-01

    Altered sialylation observed during oncogenic transformation, tumor metastases and invasion, has been associated with enhanced sialyltransferases (STs) transcription. Increased mRNA expression of STs (ST6Gal I, ST3Gal III) has been detected in invasive cervical squamous cell carcinoma. A study of the sialic acid concentration in local tissue of cervix and in serum showed a slight elevation in benign inflammatory lesions and a moderate elevation in severe neoplasia, but to date, altered expression of STs in cervical intraepithelial neoplasia has not yet been evaluated. This study investigates the changes in mRNA expression of three STs (ST6Gal I, ST3Gal III, and ST3Gal IV) in cervical intraepithelial lesions (CIN). Alterations of these STs mRNA expression were examined in 35 cervix specimens classified as normal, CIN 1, CIN 2 and CIN 3, by semiquantitative reverse transcription-polymerase chain reaction, mRNA expression of the three STs was enhanced in CIN 1, CIN 2 and CIN 3 with respect to normal tissue, with a significant difference of p altered expression of ST3Gal III, ST3Gal IV and ST6Gal I in CIN could play an important role during malignant transformation and could be related with the enhanced sialic acid expression detected in neoplasic tissues.

  4. 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

  5. CRYOTHERAPY IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Naina Kumar

    2013-01-01

    Full Text Available Cryotherapy is a time proven ablative method of treating lower grades of cervical dysplasia. It  is done using compressed CO2 or N2O refrigerant with the aim of creating an ice ball with a depth of freeze denoted by a peripheral margin of 4-5 mm of frost. It is performed using a double freeze or single freeze technique. Currently the double freeze technique of cryotherapy is an accepted treatment for mild and focal moderate dysplasia of the uterine cervix. The success of cryotherapy is determined by five factors : patient anatomy, pathology, equipment, technique and physician skill. Here we have a brief review of cryotherapy as an effective modality in treatment of lower grades of cervical intraepithelial neoplasias.

  6. 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.

  7. Human papillomavirus cervical infection: viral genotyping and risk factors for high-grade squamous intraepithelial lesion and cervix cancer

    OpenAIRE

    Vilma Guimarães de Mendonça; Maria José Bezerra Guimarães; José Luiz de Lima Filho; Carolina Guimarães de Mendonça; Danyelly Bruneska Gondim Martins; Sergio Crovella; Luiz Cláudio Arraes de Alencar

    2010-01-01

    OBJETIVO: analisar, em mulheres com HPV em colo do útero, as características da infecção viral e os fatores de risco para lesão intraepitelial de alto grau e carcinoma cervical. MÉTODOS: realizou-se um estudo caso-controle com mulheres com HPV em colo do útero atendidas em serviço de Ginecologia de referência vinculado ao SUS, em Recife, Nordeste do Brasil. No grupo de casos (72 mulheres com lesão intraepitelial de alto grau ou carcinoma cervical) e de controles (176 mulheres com colpocitolog...

  8. [Intraepithelial cervical squamous lesions: comparison between PAP-test, colposcopy, phase contrast microscopy and histology; usefulness of their synergic use].

    Science.gov (United States)

    Iuspa, F; Maruotti, G; Del Bianco, A; Di Martino, A; Celeste, T; Pietropaolo, F

    2005-04-01

    In the last 10 years the tumors of cervix have showed a significant reduction in incidence, while the preneoplastic lesions are increased (linked often to human papilloma virus [HPV] infection), and so it is enhanced the role of early diagnosis. The Authors have examined 124 patients at colposcopy showing transformation zone anomalies and/or HPV infections. The patients have submitted to PAP-test, phase contrast microscopy and to biopsy. The analysis of our cases show oneself better sensitivity of colposcopy than cytologic exam, in particular in the diagnosis of low grade intraepithelial lesions (LSIL), corresponding to CIN 1 and HPV lesions. Phase contrast microscopy, by search of possible preneoplastic elements in the smear, is a complementary technique, and if performed systematically and by qualified operators allows to reduce furthermore false negative rate. The synergic use of tools allows to increase of number of intrecervical neoplasia diagnosis. The following cost's increase cannot be considered an obstacle and it is not should be necessary to counsel always the colposcopy in case of anomalous PAP smear revealed during screening.

  9. [Diagnostic value of p16INK4a in squamous intraepithelial lesion in gynecologic cytology].

    Science.gov (United States)

    Mei, Ping; Liu, Yan-hui; Zhuang, Heng-guo; Luo, Xin-lan; Xiao, Ke-lin

    2007-08-01

    To study the diagnostic value of p16(INK4a) in squamous intraepithelial lesion in gynecologic cytology and its relationship with types of human papillomavirus (HPV). 88 liquid-based gynecologic cytology cases with histologic correlation, including 20 cases of cervicitis, 18 cases of low-grade squamous intraepithelial lesion (LSIL), 34 cases of high-grade squamous intraepithelial lesion (HSIL) and 16 cases of squamous cell carcinoma (SCC), were enrolled into the study. Immunocytochemistry for p16(INK4a) protein and polymerase chain reaction-based HPV DNA testing (for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68, as well as HPV types 6, 11, 42, 43 and 44) were performed. The rate of expression of p16(INK4a) protein was 0, 27.8%, 100% and 100% in the cervicitis group, LSIL group, HSIL group and SCC group, respectively. The expression was significantly higher in the latter 3 groups than that in the cervicitis group (P < 0.01). Besides, the expression was significantly higher in cases associated with high-risk HPV genotypes (96.4%) than in cases associated with low-risk HPV genotypes (7.7%). p16(INK4a) is a valuable biomarker for detection of HPV-related dysplastic squamous cells, with high sensitivity and specificity.

  10. Cervical intra-epithelial neoplasia and invasive cervical cancer in ...

    African Journals Online (AJOL)

    Abstract. The relative incidences of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer were studied in black and white patients at the academic hospitals of the University of the Orange Free State. ... This serious yet preventable disease is still very prevalent in South Africa, especially among black women.

  11. Clinical analysis of cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia.

    Science.gov (United States)

    He, Yue; Zhao, Qun; Geng, Yu-Ning; Yang, Shu-Li; Yin, Cheng-Hong; Wu, Yu-Mei

    2017-04-01

    The purpose of this prospective cohort study is to evaluate the importance of screening and its diagnostic accuracy compared with the pathological diagnosis of cervical intraepithelial neoplasia (CIN) with vaginal intraepithelial neoplasia (VAIN).The prospective study enrolled 419 patients (pts) and was conducted between February 1, 2015 and January 31, 2016 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University.All enrolled pts underwent multipoint biopsy of cervix and vaginal wall directed by colposcopy. All samples of biopsy underwent pathological examination. Among them, 201 pts (48.0%) were diagnosed with CIN, 218 pts (52.0%) were diagnosed with cervicitis, and 51 pts (12.2%) were diagnosed with VAIN. It was found that the incidence of CIN in pts was 4 times higher than that of VAIN. In all 419 patients enrolled, 218 pts had cervicitis with 13 pts (6.0%) of VAIN. There were 201 pts of CIN with 38 pts (18.9%) of VAIN: including 53 pts of CIN3 with 12 pts (22.6%) of VAIN; 49 pts of CIN2 with 9 pts of VAIN (18.4%), and 99 pts of CIN1 with 17 pts of VAIN (17.2%). The incidence of CIN with VAIN (18.9%) was significantly higher than cervicitis with VAIN (6.0%) (χ = 16.39, P = .00). Our results showed that there was a significant consistency between cervical lesions and vaginal lesions (χ = 135.91, P = .00), which indicated that the increase of CIN grades may be related to an increase of the VAIN grades. Our results also showed the significant (p 50 years Kappa = 0.28).This study showed that cytological test can be used as a routine screening method for cervical lesions and vaginal diseases. If the cytology result shows abnormality, and pathological examination confirms that there is no obvious abnormal cervical disease, colposcopy directed vaginal multipoint biopsy should be conducted to exclude vaginal disease. All patients of CIN should routinely undergo vaginal multipoint biopsy (1/3 upper vagina), especially in patients

  12. In vivo detection of cervical intraepithelial neoplasia by multimodal colposcopy

    Science.gov (United States)

    Ren, Wenqi; Qu, Yingjie; Pei, Jiaojiao; Xiao, Linlin; Zhang, Shiwu; Chang, Shufang; Smith, Zachary J.; Xu, Ronald X.

    2016-03-01

    Cervical cancer is the leading cause of cancer death for women in developing countries. Colposcopy plays an important role in early screening and detection of cervical intraepithelial neoplasia (CIN). In this paper, we developed a multimodal colposcopy system that combines multispectral reflectance, autofluorescence, and RGB imaging for in vivo detection of CIN, which is capable of dynamically recording multimodal data of the same region of interest (ROI). We studied the optical properties of cervical tissue to determine multi-wavelengths for different imaging modalities. Advanced algorithms based on the second derivative spectrum and the fluorescence intensity were developed to differentiate cervical tissue into two categories: squamous normal (SN) and high grade (HG) dysplasia. In the results, the kinetics of cervical reflectance and autofluorescence characteristics pre and post acetic acid application were observed and analyzed, and the image segmentation revealed good consistency with the gold standard of histopathology. Our pilot study demonstrated the clinical potential of this multimodal colposcopic system for in vivo detection of cervical cancer.

  13. Anal and cervical intraepithelial neoplasia: possible parallel.

    Science.gov (United States)

    Scholefield, J H; Sonnex, C; Talbot, I C; Palmer, J G; Whatrup, C; Mindel, A; Northover, J M

    1989-09-30

    This study evaluated prospectively the use of an endoscope in examination of the anal canal for the detection of premalignant lesions. All patients underwent endoscopy and anal epithelial biopsy; the biopsy samples were examined histologically and human papillomavirus (HPV) DNA hybridisation was done. No evidence of anal intraepithelial neoplasia (AIN) was found in 20 control patients with anal fissure or fistula. Of 82 patients with anal HPV infection, 23 had evidence of AIN. The prevalence of AIN was significantly higher among homosexual than among heterosexual men (17 of 28 vs 1 of 26) with anal HPV infection. Of 28 women with anal HPV infection, 10 had cervical intraepithelial neoplasia (CIN); 5 of the 10 also had AIN, whereas no woman had AIN in the absence of CIN. The study shows that AIN occurs and can be diagnosed endoscopically in a manner similar to CIN. Further detailed prospective studies on the natural history of AIN and of groups at risk are required.

  14. 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.

  15. 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.......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....

  16. 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...

  17. 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)

    2012-01-01

    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 < 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

  18. AgNOR polymorphism association with squamous intraepithelial lesions and invasive carcinoma with HPV infection Asociación de los polimorfismos AgNORs con lesiones intraepiteliales escamosas, carcinoma cervical e infección por VPH

    Directory of Open Access Journals (Sweden)

    Luz del Carmen Alarcón-Romero

    2009-04-01

    Full Text Available OBJECTIVE: Evaluate the relationships between AgNORs polymorphisms and squamous intraepithelial lesions (SIL and squamous cell carcinoma (SCC with HPV infection. MATERIALS AND METHODS: A study was carried out on sixty women from the state of Guerrero, Mexico. HPV detection was performed by PCR. AgNORs were identified by argentic impregnation. One hundred cells per slide were counted and classified according to the polymorphism of AgNORs dots; typical (spherical and atypical (large, kidney-shaped and clustered. RESULTS: A total of 100% of the cases were positive for HPV infection. Nine different high-risk HPV genotypes were found, type16 was the most common (48.6%. The AgNORs showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in SIL and SCC (p-trendOBJETIVO: Evaluar la relación entre los polimorfismos de AgNORs con las lesiones intraepiteliales escamosas (LIE y carcinoma de células escamosas (CCE. MATERIAL Y MÉTODOS: Se estudiaron sesenta mujeres del estado de Guerrero, México. La detección del VPH fue por PCR y los AgNORs por impregnación argéntica; se contaron 100 células y se clasificaron por tipo de polimorfismo de AgNORs: típico (esférico y atípicos (largo, forma de riñón o de racimo. RESULTADOS: El 100% de los casos presentaron infección por VPH, se encontraron nueve genotipos diferentes de VPH de alto riesgo, el 16 fue el más común (48.6%. La forma esférica de los polimorfismos de AgNORs mostró una disminución con el desarrollo neoplásico y las atípicas incrementaron progresivamente con SIL y SCC (p-tendencia<0.001. CONCLUSIONES: Los polimorfismos AgNORs se incrementan progresivamente con el grado de lesión histológica, y pueden ser útiles en el pronóstico de progresión del carcinoma cervical.

  19. Risk factors of cervical intraepithelial lesion in Douala-Cameroon ...

    African Journals Online (AJOL)

    Risk factors of cervical intraepithelial lesion in Douala-Cameroon: Implications of Herpes Simplex Virus Type 2, Chlamydia Trachomatis and Treponema Pallidum. ... Infection with high risk oncogenic human papillomavirus (HPV) such as HPVs 16 and 18 is the main cause of cervical cancer. ... a description of the source ...

  20. Epidemiology of cervical human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among a cohort of HIV-infected and uninfected Ghanaian women.

    Science.gov (United States)

    Obiri-Yeboah, Dorcas; Akakpo, Patrick K; Mutocheluh, Mohamed; Adjei-Danso, Emmanuel; Allornuvor, Gloria; Amoako-Sakyi, Daniel; Adu-Sarkodie, Yaw; Mayaud, Philippe

    2017-10-16

    There is limited data in Ghana on the epidemiology of HPV and cervical neoplasia and their associations with HIV. This study aimed to compare among HIV-1 seropositive and HIV-seronegative Ghanaian women: (1) the prevalence, genotype distribution and risk factors associated with cervical HPV infection; and (2) the prevalence and risk factors associated with abnormal cervical cytology. A comparative frequency-matched study was conducted in a systematic sample of women aged ≥18 years attending HIV and general outpatient clinics in Cape Coast Teaching Hospital, Ghana. Participants were interviewed and cervical samples collected for HPV genotyping (Seegene Anyplex-II HPV28) and cytological testing. Overall, 333 women were recruited, 163 HIV-1 seropositive and 170 HIV-seronegative women of mean age 43.8 years (SD ±9.4)) and 44.3 years (SD ±12.8), respectively. The prevalence of 14 high-risk (hr) HPV genotypes was higher among HIV-1 seropositive women (65.6% vs. 30.2%, P < 0.0001), as was proportion with multiple hr.-HPV infections (60.6% vs. 21.3%, P < 0.0001). HPV35 was the most prevalent hr.-HPV genotype in both groups (11.9% and 5.3%). The main factors associated with hr.-HPV infection were age for HIV-positive women and circumcision status of main sexual partner for both HIV-negative and positive women. Abnormal cervical cytology prevalence was higher among HIV-1 seropositive women (any SIL: 14.1% vs. 1.2%, P < 0.0001; low-grade SIL [LSIL]: 4.9% vs. 0.6%, P = 0.02; high-grade SIL: 1.8% vs. 0%, P = 0.07). Among HIV-1 seropositive women, number of pregnancies and CD4+ cell count were associated with LSIL+ cytology. There was strong association between LSIL+ abnormalities and HPV35 (aOR = 4.7, 95%CI: 1.3-17.7, P = 0.02). HIV-1 infected women bear significant burden of HPV infection and related disease. Prevention and screening programmes should be specifically deployed for this population in Ghana.

  1. Folate, vitamin C, and cervical intraepithelial neoplasia.

    Science.gov (United States)

    VanEenwyk, J; Davis, F G; Colman, N

    1992-01-01

    A case-control study was designed to assess the relationship between cervical intraepithelial neoplasia (CIN) and folate in serum, red blood cells, and diet. The association between CIN and dietary vitamin C was also investigated. Cases were selected from women with biopsy-confirmed CIN. Controls were age-, race-, and clinic-matched women with normal cervical (Pap) smears. Study participants completed self-administered food frequency (n = 100 matched pairs) and health (n = 102 matched pairs) questionnaires. Fasting venous blood samples were collected for serum (n = 98 matched pairs) and red cell (n = 68 matched pairs) folate assays. Conditional logistic regression models were used to estimate crude odds ratios and odds ratios adjusted for smoking, income, number of sexual partners, frequency of cervical smear, use of spermicidal contraceptive agents, history of genital warts, and Quetelet index. Dietary intake variables were adjusted for total energy intake prior to logistic regression. A protective effect of red cell folate was evident with adjusted odds ratios (95% confidence intervals) of 0.1 (0.0-0.4), 0.6 (0.2-2.0), and 0.5 (0.2-1.9) for those in quartiles 4 (highest), 3, and 2 compared to quartile 1 (lowest). Supporting evidence for the protective effect of folate was provided by inverse associations between CIN and folate in both serum and diet. An inverse association was also found between CIN and dietary vitamin C with adjusted odds ratios (95% confidence intervals) of 0.2 (0.0-0.7), 0.6 (0.2-1.6), and 0.6 (0.2-1.8) for those in quartiles 4, 3, and 2, respectively, compared to quartile 1. These findings support dietary recommendations, such as those of the American Cancer Society, the National Cancer Institute, and the U.S. Dietary Guidelines, which allow for adequate intake of folate and vitamin C, both of which are found in good quantity in fruits and vegetables. Increased consumption of legumes and whole grains is also in accord with current dietary

  2. 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

    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...... 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......, 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...

  3. Prediction of clinical outcome using p16INK4a immunocytochemical expression in low-grade squamous intraepithelial lesions and high-risk HPV-positive atypical squamous cells of undetermined significance in patients with and without colposcopic evident cervical disease

    Science.gov (United States)

    LUKIC, ANKICA; SBENAGLIA, GIORGIO; CARICO, ELISABETTA; DI PROPERZIO, MATILDE; GIARNIERI, ENRICO; FREGA, ANTONIO; NOBILI, FLAVIA; MOSCARINI, MASSIMO; GIOVAGNOLI, MARIA ROSARIA

    2011-01-01

    p16INK4a as a diagnostic marker of a cervical intraepithelial neoplasia of grade 2+ (CIN2+) in atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytological samples has been analyzed, but has not yet been included in clinical routine practice. One hundred and ninety-one patients with an abnormal Pap test (84 ASC-US and 107 LSILs) who underwent colposcopy were selected for this study. At enrollment, 96 patients (Group 1) had a positive colposcopy and therefore underwent a cervical biopsy, while 95 (Group 2) had a negative colposcopy and were followed up for up to 1 year. Both groups were tested for p16INK4a using immunocytochemical methods, and the p16INK4a results were correlated with histology or follow-up outcome. In Group 1 ASC-US cases, 82% of lesions less than CIN2 were p16INK4a-negative and all CIN2 cases were p16INK4a-positive (p=0.00044). In Group 1 LSIL cases, 71% of lesions less than CIN2 were p16INK4a-negative and 87% of CIN2/3 were p16INK4a-positive (p=0.00033). Seventy-seven percent of Group 2 ASC-US patients with a negative 1-year follow-up (NF-U) were p16INK4a-negative at enrollment, while all patients with positive follow-up (PF-U) were p16INK4a-positive (p=0.00113). In Group 2 LSIL cases, 83% of patients with NF-U were p16INK4a-negative, while 65% of patients with PF-U were p16INK4a-positive at enrollment (p=0.0014). In fact, 39% of the positive p16INK4a LSIL patients had CIN2+ histological lesions. The positive predictive value of p16INK4a for CIN2+ was 50% in ASC-US and 52% in LSIL cases; the negative predictive value was 100 and 94%, respectively. In conclusion, in our patients, a negative p16INK4a appears to be a marker of the absence of CIN3, while a positive p16INK4a can be correlated with the presence of histological CIN2+ found at enrollment or during the subsequent follow-up. Thus, its clinical predictive value is independent from the colposcopic aspect at enrollment. PMID

  4. 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

  5. The Anal Pap Smear: Cytomorphology of squamous intraepithelial lesions

    Directory of Open Access Journals (Sweden)

    Arain Shehla

    2005-01-01

    Full Text Available Abstract Background Anal smears are increasingly being used as a screening test for anal squamous intraepithelial lesions (ASILs. This study was undertaken to assess the usefulness and limitations of anal smears in screening for ASILs. Methods The cytomorphological features of 200 consecutive anal smears collected in liquid medium from 198 patients were studied and findings were correlated with results of surgical biopsies and/or repeat smears that became available for 71 patients within six months. Results Adequate cellularity was defined as an average of 6 or more nucleated squamous cells/hpf. A glandular/transitional component was not required for adequacy. Dysplastic cells, atypical parakeratotic cells and bi/multinucleated cells were frequent findings in ASIL while koilocytes were infrequent. Smears from LSIL cases most frequently showed mildly dysplastic and bi/multinucleate squamous cells followed by parakeratotic cells (PK, atypical parakeratotic cells (APK, and koilocytes. HSIL smears contained squamous cells with features of moderate/severe dysplasia and many APKs. Features of LSIL were also found in most HSIL smears. Conclusions In this study liquid based anal smears had a high sensitivity (98% for detection of ASIL but a low specificity (50% for predicting the severity of the abnormality in subsequent biopsy. Patients with cytologic diagnoses of ASC-US and LSIL had a significant risk (46–56% of HSIL at biopsy. We suggest that all patients with a diagnosis of ASC-US and above be recommended for high resolution anoscopy with biopsy.

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

    OpenAIRE

    do Socorro Nobre, Maria; Jacyntho, Claudia Marcia; Eleutério Jr., José; Giraldo, Paulo César; Gonçalves, Ana Katherine

    2016-01-01

    Abstract 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 ide...

  7. Infecção cervical por papilomavírus humano: genotipagem viral e fatores de risco para lesão intraepitelial de alto grau e câncer de colo do útero Human papillomavirus cervical infection: viral genotyping and risk factors for high-grade squamous intraepithelial lesion and cervix cancer

    Directory of Open Access Journals (Sweden)

    Vilma Guimarães de Mendonça

    2010-10-01

    ômicos, reprodutivos e relacionados à ausência de rastreamento citológico representam risco para lesão intraepitelial de alto grau e câncer cervical.PURPOSE: to analyze the characteristics of viral infection and the risk factors for high-grade squamous intraepithelial lesion and cervical carcinoma in women with cervical HPV infection. METHODS: a case-control study was conducted on women with cervical HPV at a Gynecology reference service enrolled at the Public Health System, located in Recife, Northeastern Brazil. The groups of cases (72 women with high-grade squamous intraepithelial lesion or cervical cancer and controls (176 women with normal Pap smear or benign alterations were investigated for six viral genotypes (HPV 16, 18, 31, 33, 6, 11 in ecto- and endocervical material using MY09/MY11 primers. The independent variables were ranked in three levels of determination: distal (sociodemographic, intermediate (behavioral and proximal (previous Pap smear. The homogeneity of proportions was tested (χ2, unadjusted Odds Ratios (OR were obtained and hierarchical logistic regression was applied to the final model, with adjustment of the effect of each variable to the outcome based on the variables in the same and previous levels of causality. RESULTS: the viral genotype of cervical infection was identified in 76.6% of the 248 women participating in the study. High-risk HPV genotypes (83.4% of cases and 67.1% of controls were predominant, especially HPV 16 and 31. The distal risk factors identified were: living in a rural area (OR=2.71, 95%CI: 1.18-6.23, less than three years of study (OR=3.97, 95%CI: 2.09-7.54 and family income below two minimum wages (OR=3.30, 95%CI: 1.04-10.51; intermediate: four or more pregnancies (OR=2.00, 95%CI: 1.06-3.76; and proximal: absence of a previous Pap smear (OR=9.74, 95%CI: 2.48-38.28. CONCLUSIONS: genotypes 16 and 31 of cervical HPV infection are predominant among women assisted by the Public Health System in Northeastern Brazil. Socioeconomic and

  8. Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

    Directory of Open Access Journals (Sweden)

    Yu. N. Ponomareva

    2010-01-01

    Full Text Available The authors have made a complex analysis of the molecular biological factors associated with cervical intraepithelial neoplasia. They have revealed that infection by oncogenic human papillomavirus types is associated with suppressed apoptosis and enhanced cellular proliferative activity, which can be effectively used in the diagnosis and prediction of cervical neoplasias to optimize management tac- tics and to improve the results of treatment.

  9. An evaluation of treatment modalities in cervical intra-epithelial ...

    African Journals Online (AJOL)

    The scheme of management of cervical 'intraepithelial neoplasia presently utilized in the colposcopy service at Groote Schuur Hospital, Cape Town, is outlined, and the results of the treatment of 721 patients with the various modalities currently available are analysed. It is concluded that a radical approach (total ...

  10. RESEARCH Cervical intra-epithelial neoplasia in HIV-positive ...

    African Journals Online (AJOL)

    However, in patients treated for cervical intra-epithelial neoplasia (CIN), the risk of developing cancer is still 2.8 times greater than in the general population, and may be more in women with recurrent disease.5 Studies show that the recurrence of CIN after treatment was between 20% and 65% in HIV-infected women.6,7.

  11. The clinical application of HPV E6/E7 mRNA testing in triaging women with atypical squamous cells of undetermined significance or low-grade squamous intra-epithelial lesion Pap smear: A meta-analysis

    OpenAIRE

    Li Yang; Yuanhang Zhu; Yang Bai; Xiaoan Zhang; Chenchen Ren

    2017-01-01

    Objective: The aim is to evaluate the clinical application value and correlation with cervical lesions' progression of human papillomavirus (HPV) E6/E7 mRNA test in women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intraepithelial lesions (LSILs/mild dyskaryosis) cytological abnormalities. Methods: A meta-analysis was conduct by searching China National Knowledge Infrastructure (1979–2016), Wanfang Date (1998–2016), VIP (1989–2016), Pu...

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

    Science.gov (United States)

    do Socorro Nobre, Maria; Jacyntho, Claudia Marcia; Eleutério, José; Giraldo, Paulo César; Gonçalves, Ana Katherine

    2016-01-01

    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. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Prevalence of cervical intraepithelial neoplasia in Zaria

    African Journals Online (AJOL)

    Preventing cervical cancer: Unprecedented opportunities for improving women's health. Outlook 2007;1:23. 2. Roblyer D, Richards-Kortum R, Park SY, Adewole I,. Follen M. Objective screening for cervical cancer in developing nations: Lessons from Nigeria. Gynecol Oncol. 2007;107:S94-7. 3. Ayangbade O,Akinyemi A.

  15. 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....

  16. Fertility and Early Pregnancy Outcomes Following Conservative Treatment for Cervical Intraepithelial Neoplasia and Early Cervical Cancer.

    Science.gov (United States)

    Kyrgiou, Maria; Mitra, Anita; Paraskevaidis, Evangelos

    2016-11-01

    Does local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer adversely affect successful conception and early pregnancy outcomes in the first and second trimester (treatment does not adversely affect fertility or first trimester miscarriage, although it is associated with a significant increase in the risk of second trimester miscarriages.

  17. 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.

  18. Human Papillomavirus Test for Triage of Japanese Women With Low-Grade Squamous Intraepithelial Lesions.

    Science.gov (United States)

    Iwata, Takashi; Hasegawa, Toshihiko; Ochiai, Kazunori; Takizawa, Ken; Umezawa, Satoshi; Kuramoto, Hiroyuki; Ohmura, Mineo; Kubushiro, Kaneyuki; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Watanabe, Kayoko; Aoki, Daisuke

    2015-12-01

    We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions. © The Author(s) 2015.

  19. Effect of the treatment with β-glucan in women with cervical cytologic report of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (L-SIL).

    Science.gov (United States)

    Laccetta, G; Carrone, A; Burratti, M; Mancino, P

    2015-04-01

    The aim of this study was to evaluate the effect of β-glucan in women with ASCUS or L-SIL, as detected by cervical cytologic screening. A total of 356 women with ASCUS or L-SIL were enrolled and divided into two groups: 1) 176 patients, treated with topical β-glucan; and 2) 180 patients who were only followed-up. The treatment consisted of two cycles of topical β-glucan applied once a day for 20 consecutive days and treatment separated by ten days. The effect of β-glucan was evaluated comparing Pap cytology results and colposcopic findings between treated patients and controls after 6 and 12 months of follow-up. After 6 months from enrollment, 63.1% (111/176) of patients treated with β-glucan had a negative Pap smear versus 45% (81/180) of controls (P<0.001), and 43.4% (36/83) of treated patients versus 18.2% (14/77) of controls experienced the disappearance of colposcopic lesions (P=0.001). At the end of the 12-month follow up, 83.5% (147/176) of treated patients versus 60% (108/180) of controls had a negative Pap smear (P<0.001), and 55.4% (46/83) of treated patients versus 24.7% (19/77) of controls experienced the disappearance of colposcopic lesions (P<0.001). No side effects were observed in treated patients. β-glucan increases the spontaneous regression rate of low-grade cytologic abnormalities as well as cervical findings.

  20. 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...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...... statistical testing, we estimated the statistical significance of the differences between the compared groups using unpaired t tests. MAIN RESULTS: From 5099 retrieved abstracts, 16 studies were included. Diagnosis and treatment of CIN were associated with worse psychological outcomes than normal cytology...

  2. 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.

  3. Utility of Human Papillomavirus Genotyping in the Management of Low-Grade Squamous Intraepithelial Lesions.

    Science.gov (United States)

    Solé-Sedeno, Josep M; Mancebo, Gemma; Miralpeix, Ester; Lloveras, Belen; Bellosillo, Beatriz; Alameda, Francesc; Carreras, Ramon

    2018-01-01

    The aim of the study was to determine the usefulness of human papillomavirus (HPV) partial genotyping test in the triage of newly diagnosed low-grade squamous intraepithelial lesions (LSILs). We analyzed 143 patients with LSIL diagnosed de novo. Lesions were classified as positive for HPV 16 or HPV 18, positive for HPV but not HPV 16 or HPV 18 (HPVno16no18) or no HPV detected (HPVneg). Patients were followed for a period of 2 years or until the lesion progressed. We calculated absolute and relative risks for progression and regression according to the HPV result. The mean (SD) age was 33.8 (11.1) years. A total of 19.6% were positive for HPV 16, 4.9% for HPV 18, and 63.6% for HPVno16no18. The absolute risk of HPV 16 for progression to cervical intraepithelial neoplasia grade 2 or more (CIN 2+) was 32.1%, 14.3% for HPV 18, and 5.8% for HPVno16no18. None of the HPVneg cases evolved to CIN 2+. The presence of HPV 16 conferred a 7.4 (95% CI = 2.7-20.3) times greater risk of developing CIN 2+ than its absence. The absolute risks for HPV 16, HPV 18, HPVno16no18, and HPVneg for regression were 53.6%, 57.1%, 75.4%, and 87.5%, respectively. Relative risks for regression were 0.7 (95% CI = 0.5-0.9) for HPV 16 and 1.3 (95% CI = 1.1-1.5) for HPVneg. The HPV 16 LSILs are more likely to progress to CIN 2+, so tight control and immediate colposcopy are crucial, whereas when HPV 16 is not present, follow-up could be less strict. Low-grade squamous intraepithelial lesions in which high-risk HPV is not detected do not progress to CIN 2+, so its control should be different from other LSIL, and conservative management could be an acceptable strategy.

  4. Detection of Actinomyces spp. in cervical exudates from women with cervical intraepithelial neoplasia or cervical cancer.

    Science.gov (United States)

    García-García, Alejandra; Coronel-Martínez, Jaime; Leon, David Cantú-de; Romero-Figueroa, María Del Socorro; Caballero-Pantoja, Yolanda Elizabeth; Manzanares-Leal, Gauddy Lizeth; Rodriguez-Morales, Miguel; Sandoval-Trujillo, Horacio; Ramírez-Durán, Ninfa

    2017-06-01

    Under certain circumstances, Actinomyces behaves as an opportunistic microorganism and can cause actinomycosis, a chronic and inflammatory granulomatous infection. The purpose of this project was to detect the presence of Actinomyces in cervical exudates from women with cervical intraepithelial neoplasia (CIN) and women with cervical cancer. Cervical samples from 92 women were divided into three groups: CIN, cervical cancer and healthy women. Metagenomic DNA extraction was performed following the Qiagen QIAamp Mini Kit protocol. A specific fragment (675 bp) was amplified by PCR in order to detect the presence of Actinomycetales. Samples in which Actinomycetales was detected were subjected to separate amplification reactions with primer pairs for A. israelii, A. viscosus, A. meyeri and A. odontolyticus. Amplified products were observed by 2 % agarose gel electrophoresis. Actinomyces were found in 10 % of women with CIN, 36.6 % of women with cervical cancer and 9 % of healthy women. The species identified in this study were A. meyeri in 14/92 samples (15.2 %), A. viscosus in 10/92 samples (10.8 %), A. odontolyticus in 4/92 samples (4.3 %) and A. israelii in 6/92 samples (6.5 %). Patients with cervical cancer had a higher prevalence of the presence of Actinomyces compared to the CIN and control groups. This is the first study in which a deliberate search of this genus has been performed in women with cervical pathologies. The use of specific primers for each species facilitated their detection in comparison with traditional isolation methods. More information is necessary to understand the molecular mechanisms involved in the complex role that bacterial communities may play in the development of cancer (and vice versa).

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

    Science.gov (United States)

    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.

  6. 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%.

  7. A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Boris Léonard

    2014-01-01

    Full Text Available Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV. Vulvar intraepithelial neoplasia (VIN and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases.

  8. Mild Obesity, Physical Activity, Calorie Intake, and the Risks of Cervical Intraepithelial Neoplasia and Cervical Cancer

    OpenAIRE

    Jae Kwan Lee; So, Kyeong A; Piyathilake, Chandrika J.; Mi Kyung Kim

    2013-01-01

    OBJECTIVE: We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: We enrolled 1125 women (age, 18-65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index...

  9. Cervical intra-epithelial neoplasia and invasive cervical cancer in ...

    African Journals Online (AJOL)

    neoplasia (CIN) and invasive cervical cancer were studied in black and white patients at ... cervical cancer. This serious yet preventable disease is still very prevalent in South Africa, especially among black women. S AIr Med J 1994; 84: 18-19. Aanalysis of rime trends in .... Dietary vitamin A and the risk of invasive cerncal ...

  10. Beta-carotene levels in exfoliated cervicovaginal epithelial cells in cervical intraepithelial neoplasia and cervical cancer.

    Science.gov (United States)

    Palan, P R; Mikhail, M S; Basu, J; Romney, S L

    1992-12-01

    The purpose of this study was to measure beta-carotene levels in exfoliated epithelial cervicovaginal cells collected by a lavage technique in normal women and patients with histopathologically diagnosed cervical intraepithelial neoplasia and cervical cancer. In a cross-sectional sampling of women (n = 105), cervicovaginal cells and plasma beta-carotene levels were assayed with high-pressure liquid chromatography. In addition, beta-carotene levels were measured in exfoliated epithelial samples of cervicovaginal cells obtained from women (n = 24) enrolled in an ongoing oral beta-carotene supplementation clinical trial. Cervicovaginal cells and plasma beta-carotene levels were found to be significantly decreased in women with cervical intraepithelial neoplasia and cervical cancer as compared with controls (p < 0.0001, analysis of variance). Retinol levels in cervicovaginal cells were undetectable. The beta-carotene levels in cervicovaginal cells were markedly increased in the majority of patients (79%) after oral supplementation as compared with baseline levels in women enrolled in the beta-carotene clinical trial. The study demonstrates that changes of in situ cellular beta-carotene concentrations are measurable in samples of exfoliated epithelial cells obtained by a noninvasive saline lavage harvesting technique. The current findings further support our previous hypothesis that beta-carotene deficiency may have an etiologic role in the pathogenesis of cervical intraepithelial neoplasia and/or cervical cancer.

  11. "SPECIMEN ADEQUACY AND EFFECT OF HUMAN PAPILLOMAVIRUS IN CERVICOVAGINAL SMEARS WITH SQUAMOUS INTRAEPITHELIAL ABNORMALITY"

    Directory of Open Access Journals (Sweden)

    N. Izadi Mood T. Hacopian

    2004-08-01

    Full Text Available Abstract-Cervicovaginal cytology is still a widely used cancer screening method that is well established in most countries. The present study aims at detecting and classifying squamous intraepithelial abnormalities and effects of certain infectious agents, particularly the cytopathic effects of human papillomavirus (HPV in a series of cervicovaginal smears, according to the Bethesda system (TBS. The significance of specimen adequacy in revealing squamous intraepithelial abnormalities (SIEA was also evaluated. Overall, 9066 smears were examined according to TBS. For interpretation of atypical squamous cell of undetermined significance (ASCUS, certain quality control (QC guidelines were considered. While stressing on koilocytic atypia, the full spectrum of cytologic alterations due to HPV was investigated. Of all smears, 79% were satisfactory for evaluation and 15% were inadequately satisfactory due to absence of the endocervical/transformation zone (EC/TZ component. The proportion of SIEA was significantly (P< 0.05 higher in smears having such a component. Of 246 cases with SIEA, 173 (1.90% cases were classified as ASCUS, 46 (0.50% as low grade squamous intraepithelial lesion (LSIL, and 27 (0.26% as high grade squamous intraepithelial lesions (HSIL. Of the latter, 19 cases demonstrated HPV effects. ASCUS was the most frequent diagnosis for which QC criteria were fulfilled. On the basis of our study the adequacy of specimen is of paramount significance, with particular emphasis on the presence of EC/TZ component.

  12. [Analysis of diagnosis and treatment of vaginal intraepithelial neoplasia and correlation to cervical intraepithelial neoplasia].

    Science.gov (United States)

    Li, Hua; Geng, Li; Guo, Yan-li; Guo, Hong-yan; You, Ke; Qiao, Jie

    2009-03-01

    To investigate the diagnosis and therapy of vaginal intraepithelial neoplasia (VAIN) and correlation to cervical intraepithelial neoplasia (CIN). The clinical and pathological data about age, liquid-based cytology, human papillomavirus (HPV) DNA test, colposcopy, histology types and treatment in 35 patients with VAIN were reviewed to investigate the diagnosis and therapy of VAIN and correlation to CIN. Mean age at presentation was 43.9 years. The percentage of VAINI, VAINII and VAINIII were 52% (18/35), 34% (12/35) and 14% (5/35), respectively. 8% (1/13) of patients were younger than 40 years developed VAINIII, while 18% (4/22) patients were elder than 40 years. There were 83% (29/35) cases were diagnosed from 2007 to June 2008. 69% (24/35) or 17% (6/35) cases had the history of CIN or cervical cancer, respectively. VAINII-III accounted for 3/9, 53% (8/15) and 4/6 of CINI, CINII-III and cervical cancer, respectively. There were 87% (13/15) positive high risk HPV infection in VAINI, while 100% in VAINII and VAINIII. There were 97% (33/34) cases with abnormality for liquid-based cytology and 86% (30/35) cases of lesions were located in the upper 1/3 vagina. Among 19 cases received therapy, 14 cases (74%) were treated by surgery, 2 cases (11%) by brachytherapy, 3 cases (16%) used drug on the surface of vagina and the lesions were shown recovery in 9 cases followed up. The clinical characteristics of VAIN are similar to CIN and the principles of diagnosis and treatment are also the same as that of CIN.

  13. 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...... 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). RESULTS: A history of CIN3/AIS was significantly...

  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

    Directory of Open Access Journals (Sweden)

    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. HPV 16 Is Related to the Progression of Cervical Intraepithelial Neoplasia Grade 2: A Case Series

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    Maria Gabriela Loffredo D’Ottaviano

    2013-01-01

    Full Text Available Purpose. To describe the acquisition, persistence, and clearance of HPV infection in women with CIN 2 followed up for 12 months. Methods. Thirty-seven women with CIN 2 biopsy, who have proven referral to cervical smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and tested for HPV, were followed up for one year with cervical smear, colposcopy, and HPV test every three months. HPV DNA was detected by the polymerase chain reaction and genotyping by reverse line blot hybridization assay. Results. CIN 2 regression rate was 49% (18/37, persistence as CIN 1 or CIN 2 was 22% (8/37, and progression to CIN 3 was 29% (11/37. Multiple HPV types were observed at admission in 41% (15/37 of cases. HPV 16 was detected at admission in 58% (11/19 of the cases that persisted/progressed and in 39% (7/18 of the cases that regressed. HPV 16 was considered possibly causal in 67% (10/15 of the cases that persisted or progressed and in 10% (1/10 of the cases that regressed (P=0.01. Conclusion. Multiple HPV infections were frequently detected among women with CIN 2 at admission and during the followup. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3.

  16. [The detection of human papillomavirus 16, 18, 35 and 58 in cervical-uterine cancer and advanced degree of squamous intraepithelial lesions in Western Mexico: clinical-molecular correlation].

    Science.gov (United States)

    Montoya-Fuentes, H; Suárez Rincón, A E; Ramírez-Muñoz, M P; Arévalo-Lagunas, I; Morán Moguel, M C; Gallegos Arreola, M P; Flores-Martínez, S E; Rosales Quintana, S; Sánchez Corona, J

    2001-04-01

    The purposes of this study were to estimate the infection frequency of Human Papilomavirus (HPV) and to identify the viral types in patients with diagnosis of uterine cervical cancer (UCC) and High Grade Squamous Intraepitelial lesions (HGSILs), and to correlate the molecular findings versus HPV infection suggestive clinical findings. Biopsies from 50 patients (37 HGSILs and 13 UCC) histopathologically diagnosed were studied. The presence of HPV were detected by means of the polymerase chain reaction (PCR) using consensus primers for types 6, 11, 16, 18, 31, 33, 35, and 58 among others, as well as specific primers for some of them. The frequencies for HPV 16, 18, 33, 35, and 58 in HGSIL samples were 24.3, 2.7, 0, 5.4 and 16.2% respectively. In UCC samples were 61.5, 7.7, 0, 0 and 15.4% with significative differences only for HPV 16. Clinical findings (histologic, colposcopic and histopathologic), showed deficient diagnostic accuracy in the identification of HPV 16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV. These results are similar to those previously described in our country and the other populations, with the exception of HPV16 in HGSIL, wich resulted less frequent and there is a high frequency of HPV 58 in our region. When analyzing clinical features with the presence of HPV DNA, we conclude that these are insufficient to discard or establish the possibility of HPV infection in patients with HGSIL's and UUC.

  17. Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

    Science.gov (United States)

    Palan, Prabhudas R; Woodall, Angela L; Anderson, Patrick S; Mikhail, Magdy S

    2004-05-01

    alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.

  18. Hemangioma of uterine cervix associated with high-grade squamous intraepithelial lesion

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    Đolai Matilda

    2015-01-01

    Full Text Available Introduction. Benign, especially polypoid, lesions of the cervix are common in everyday work. Rare tumors of this region are vascular ones, particularly capillary and/or cavernous hemangiomas. Cervical hemangiomas are especially rare, usually asymptomatic and only one third of the cases is clinically manifested as vaginal bleeding, polyps, etc. Case report. We reported a 54-year-old postmenopausal female patient who had undergone conization due to high-grade squamous intra-epithelial lesion (H-SIL. Microscopic analysis of slices confirmed the existence of dysplastic changes in the endocervical epithelium and in small part in the epithelium of the gland of H-SIL type. In 2 of 15 slices, within the walls of the cervix, dilated, amplified and abnormal blood vessels lined with endothelium were observed, vaguely limited by the surrounding connective tissue of lamina propria and smooth muscle wall of the cervix. According to the pathological characteristics, the change corresponded to the hemangioma. Both changes were completely removed. Conclusion. In comparison with the available literature data, the presented case is the first to describe the association of hemangioma and dysplastic changes in the endocervical epithelium. Hemangioma was incidentally discovered in the histological sections of the material after the conization in a postmenopausal women.

  19. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    Science.gov (United States)

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis.

  20. Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men.

    Science.gov (United States)

    Keglovitz, Kristin; Richardson, Andrew D; Lancki, Nicola; Walsh, Tim; Schneider, John A

    2017-02-01

    Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Results of anal cytology and HPV DNA were gathered for 83 individuals. Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV.

  1. Description of patients with squamous cell carcinoma in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion triage study.

    Science.gov (United States)

    Atkins, Kristen A; Jeronimo, Jose; Stoler, Mark H

    2006-08-25

    The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) accumulated information regarding conventional and liquid-based Papanicolaou (Pap) cytology, 2 kinds of human papillomavirus (HPV) DNA testing, cervicography, and colposcopically directed biopsy. The prevalence of squamous cell carcinoma in these women, the efficacy of tests, and the time to detection were reviewed. The ALTS data base was reviewed for all women with invasive carcinoma. All results of colposcopy, HPV testing, cytology, biopsies, and cervigrams were reviewed for all women in the ALTS trial who were diagnosed with squamous cell carcinoma. There were 7 diagnoses of invasive cancer (all squamous cell) during the 2 years of the ALTS trial. Although the enrollment studies isolated many high-grade lesions, none of those results were diagnostic of the underlying carcinoma. The prevalence of squamous cell carcinoma in the setting of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology interpretation appears to be low (approximately 1 per 1000 women in the ALTS trial). Many of the carcinomas were not visible on the ectocervix by cervicography or colposcopy, which may explain in part the paucity of atypical cells detected on the Pap tests and the finding that the presenting cytology, although abnormal, was never diagnostic of cancer. HPV DNA tests were positive in all 7 cancers. Type-specific testing identified HPV type 16 in 6 of 7 cancers and HPV type 18 in 1 of 7 cancers. Copyright 2006 American Cancer Society.

  2. Detection and genotyping of HPV in women with indeterminate cytology and low-grade squamous intraepithelial lesions

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    Francisca A. Queiroz

    2015-06-01

    Full Text Available ABSTRACT Introduction: The human papillomavirus (HPV is the main risk factor related to cervical cancer, the third most frequent type of cancer in Brazilian women. Early identification of high-risk HPV types in the normal cervix, or cervix with premalignant lesions may help prevent the progression of these lesions to cancer. Objective: This study aimed to detect and genotype HPV in women with low-grade intraepithelial lesion (LSIL and atypical squamous cells of undetermined significance (ASC-US. Methods: Patients were selected from files of the cytology laboratory of Fundação Alfredo da Mata (FUAM, between January 2009 and July 2011, for cytological reassessment and HPV molecular detection with genotyping. Results: Out of the100 eligible patients, 70% (70/100 participated in the study; initially, 34 of them had ASC-US and 36 had LSIL. After cytological reassessment, eight (11.4% patients showed normal cytology; 33 (47.2%, inflammatory lesions; 22 (31.4%, ASCUS; six (8.6%, LSIL; and one (1.4%, high-grade squamous intraepithelial lesions (HSIL. HPV was detected in 28.6% (20/70 of the samples. Out of the 20 HPV-positive patients, one had normal cytology, six showed inflammatory cytology, 10 showed ASCUS, two had LSIL and one, HSIL. After genotyping, the HPV types identified were: 6, 16, 58, 61, 70, 83, 84 and 85. The most prevalent HPV type was the 58. Conclusion: The presence of high-risk HPV in women with old cervical lesions, whether they have evolved or not, indicates the need to improve patient monitoring and surveillance.

  3. 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.

  4. Circulation of human papillomavirus (HPV genotypes in women from Córdoba, Argentina, with squamous intraepithelial lesions

    Directory of Open Access Journals (Sweden)

    Raul Fernando Venezuela

    2012-02-01

    Full Text Available Human papillomavirus (HPV can induce a wide spectrum of squamous intraepithelial lesions (SIL of varying severity. The aim of the present study was to establish the frequency of HPV infection and identify the genotypes circulating in women from Córdoba, Argentina, in relation to age and cytology. A total of 186 women, between 18 and 65 years old, with antecedents of SIL, underwent a pelvic examination and had cervical cells collected for cytology and HPV DNA detection. Ninety-six samples (51.6% were positive for HPV detection, and sixty-three (65.6% of them showed the presence of at least one HR-HPV. Low- and high-grade SIL showed significant association in patients younger than 35 years of age. We found 18 different genotypes, with a greater presence of HR-HPV. Genotypes 16 and 6 were the most frequent. Seven (7.3% multiple infections, 85.7% of which had at least one HR-HPV, were detected. The detection of a large number of different HPV genotypes is a warning sign. It is thus necessary to strengthen the monitoring of the circulation of high-risk genotypes, currently less prevalent in intraepithelial lesions, as a control measure for the possible impact of the implementation of vaccines against genotypes 16 and 18.

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

    Science.gov (United States)

    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.

  6. Plasma uric acid levels in women with cervical intraepithelial neoplasia.

    Science.gov (United States)

    Basu, Jayasri; Mikhail, Magdy S; Ahn, Chul W; Furguiele, Joseph; Ho, Gloria Y; Burk, Robert D; Palan, Prabhudas R; Romney, Seymour L

    2005-01-01

    The objective of this study was to determine the association of plasma levels of uric acid, an endogenous antioxidant, in women with cervical intraepithelial neoplasia (CIN), while controlling for the confounding effects of human papillomavirus (HPV) infection, age, smoking, and use of oral contraception. Plasma-reduced and oxidized uric acid levels were determined in 650 women by high-performance liquid chromatography, employing electrochemical technique. The findings demonstrated that 1) plasma-reduced uric acid (PRUA) levels in women with CIN (n = 311) were significantly lower (P < 0.05) compared with women in a control group (n = 339); 2) according to multiple logistic regression analysis, PRUA levels were negatively (P = 0.0113) and HPV infection were positively associated (P < 0.0001) with CIN, after controlling for the confounding effects of the studied factors; 3) according to multiple regression analysis, there was a 31% decrease in CIN risk for each incremental increase of 1mg/dl of PRUA; and 4) according to polychotomous logistic regression analysis, independent of HPV infection, PRUA level was inversely associated with the histopathological graded severity of CIN. We have previously reported decreased plasma levels of exogenous antioxidants, for example, vitamins C and E, in women with CIN independent of HPV infection. The data suggest that plasma deficiencies of several antioxidants in HPV-infected uterine cervical tissue may create an oxidative environment that renders the tissue susceptible to free radical damage. It may be speculated that chronic free radical-induced tissue damage in the context of persistent HPV infection may be involved in the pathogenesis of CIN.

  7. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

    NARCIS (Netherlands)

    Siegenbeek van Heukelom, Matthijs L.; Marra, Elske; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.; Prins, Jan M.

    2017-01-01

    HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive

  8. 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...

  9. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Jing Rui Tang

    Full Text Available Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM versus low grade squamous intraepithelial lesion (LSIL, NILM versus high grade squamous intraepithelial lesion (HSIL, and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells.

  10. Clinical Significance of Atypical Squamous Cells of Undetermined Significance among Patients Undergoing Cervical Conization.

    Science.gov (United States)

    Nishimura, Mai; Miyatake, Takashi; Nakashima, Ayaka; Miyoshi, Ai; Mimura, Mayuko; Nagamatsu, Masaaki; Ogita, Kazuhide; Yokoi, Takeshi

    2015-01-01

    Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease.

  11. Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

    Science.gov (United States)

    Heráclio, Sandra A; de Souza, Alex S R; de Souza, Paulo R E; Katz, Leila; Lima Junior, Sergio F; Amorim, Melania M R

    2018-02-01

    To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (Panal intraepithelial neoplasia. The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years. © 2017 International Federation of Gynecology and Obstetrics.

  12. Cervical and Vulvar Intraepithelial Neoplasia after Treatment with Oral Isotretinoin for Severe Acne Vulgaris

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    M.N. Al Hallak

    2009-09-01

    Full Text Available Oral isotretinoin is the drug of choice for severe acne vulgaris, but its use is still controversial in preventing, treating or stopping the progression of the cervical intraepithelial neoplasia [6–8]. It induces cell differentiation, inhibits cell proliferation, stimulates host immune reaction, inhibits the oncogene expression, augments cell-mediated cytotoxicity, and induces apoptosis [5]. The isotretinoin has many side effects including teratogenicity. There is no previous report of developing cervical intraepithelial neoplasia (CIN or vulvar intraepithelial neoplasia (VIN after introducing oral isotretinoin to a patient. We are reporting a 37-year-old female with no risk factors for cervical cancer who had developed CIN-I and VIN-I during a 6-month treatment period of oral isotretinoin for her severe acne vulgaris. Interestingly, the patient had complete spontaneous pathologic-proven remission after stopping the isotretinoin. Further case reports are warranted to support this incidence.

  13. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

    Science.gov (United States)

    Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M

    2017-02-07

    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

  14. Mild obesity, physical activity, calorie intake, and the risks of cervical intraepithelial neoplasia and cervical cancer.

    Science.gov (United States)

    Lee, Jae Kwan; So, Kyeong A; Piyathilake, Chandrika J; Kim, Mi Kyung

    2013-01-01

    We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. We enrolled 1125 women (age, 18-65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5-23 kg/m(2)), the multivariate ORs (95% CIs) for those overweight (23-25 kg/m(2)) and mild obesity (≥25 kg/m(2)) were 1.25 (0.79-2.00) and 1.70 (1.10-2.63), respectively. When compared with women with the lowest tertile of physical activity (cervical cancer were 0.95 (0.61-1.48) and 0.61 (0.38-0.98) for women with medium physical activity (38.5-71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend  = 0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (cervical cancer after adjustment for confounders. Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer.

  15. Misdiagnosis of high-grade vulvar intraepithelial neoplasia (VIN III) as mild cervical intraepithelial neoplasia (CIN I) on Papanicolaou tests.

    Science.gov (United States)

    August, Carey Z; Ganji, Masoud; Froula, Evelyn

    2003-01-01

    Although high-grade vulvar intraepithelial neoplasia (VIN III) is a clinically significant lesion, it can be overlooked because of nonspecific clinical findings and the fact that its cytomorphologic features mimic those of mild cervical intraepithelial neoplasia (CIN I). To determine if there are cytomorphologic features on Papanicolaou tests that can reliably distinguish between VIN III and CIN I. Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven CIN I were compared with Papanicolaou tests diagnosed as CIN I from patients with biopsy-proven VIN III but with no biopsy-proven CIN I. None of the cytomorphologic features evaluated could reliably distinguish CIN I from VIN III. Since the Papanicolaou test cannot be used to distinguish between CIN I and VIN III, the clinician must pay careful attention to the clinical and colposcopic findings. Further research evaluating the use of ancillary studies, such as human papillomavirus typing, may be useful.

  16. 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.

  17. 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.

  18. MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression

    OpenAIRE

    Toll, Agust?; Salgado, Roc?o; Espinet, Blanca; D?az-Lagares, Angel; Hern?ndez-Ruiz, Eugenia; Andrades, Evelyn; Sandoval, Juan; Esteller, Manel; Pujol, Ram?n M; Hern?ndez-Mu?oz, Inmaculada

    2016-01-01

    Background Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited. Methods Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyros...

  19. Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer.

    Science.gov (United States)

    Palan, P R; Mikhail, M S; Shaban, D W; Romney, S L

    2003-08-01

    Cervical intraepithelial neoplasia (CIN) may, at times, unpredictably progress to invasive carcinoma of the cervix. Epidemiological nutritional studies suggest that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical cancer. However, a preventive role of dietary antioxidants in CIN is not well established. The purpose of this cross-sectional study was to investigate the comparative plasma concentrations of three potent antioxidants, coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol, in women with normal Pap smears and patients with a biopsy-confirmed histopathological lesion diagnosed as CIN or cervical cancer. Plasma concentrations of coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography in both normal women without any history of abnormal Pap smears (n=48), and patients with histopathologically confirmed diagnoses of: (a) CIN I, n=98; (b) CIN II, n=49; (c) CIN III, n=10; and (d) cervical cancer, n=25. The mean plasma levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were significantly lower (P<0.001,<0.001, and<0.001, respectively by Kruskal-Wallis test) in patients with various grades of CIN and cervical cancer compared with controls. After controlling for age and smoking, an inverse association between histological grades of epithelial lesions and both plasma coenzyme Q(10) and alpha-tocopherol concentrations was observed. The low plasma concentrations of coenzyme Q(10) may be due to deficient dietary intake or a decrease in endogenous coenzyme Q(10) biosynthesis that may reflect increased utilization as a result of free radical reactive oxygen species induced oxidative stress. Further molecular studies on the mechanistic role of antioxidants in women with precancer cervical lesions are needed.

  20. Performance of the HPV-16 L1 methylation assay and HPV E6/E7 mRNA test for the detection of squamous intraepithelial lesions in cervical cytological samples.

    Science.gov (United States)

    Qiu, Cui; Zhi, Yanfang; Shen, Yong; Gong, Jiaomei; Li, Ya; Rong, Shouhua; Okunieff, Paul; Zhang, Lulu; Li, Xiaofu

    2015-11-01

    HPV-16 L1 methylation and E6/E7 mRNA have suggested that they had close relationship with cervical neoplastic progression. This study aimed to evaluate the clinical performance of the HPV-16 L1 methylation assay and E6/E7 mRNA test for detecting high-grade cervical lesions (CIN2+). A total of 81 women with liquid-based cytology (LBC) samples, histological results, and positive HPV-DNA test for HPV type 16 only were included in this study. HPV-16 L1 methylation and E6/E7 mRNA levels were measured using methylation-sensitive high resolution melting (MS-HRM) analysis and Quantivirus®HPV E6/E7 RNA 3.0 assay (bDNA), respectively, in the same residue of LBC samples. The current date showed a positive correlation between the HPV-16 L1 methylation and the E6/E7 mRNA levels. The L1 methylation and mRNA levels both increased with disease severity. The mRNA test method showed higher sensitivity and NPV (98.0 and 91.7% vs. 89.8 and 80.8%), while lower specificity and PPV (34.4 and 69.6% vs. 65.6 and 80.0%), than the L1 methylation assay for detecting histology-confirmed CIN2+. When using the detection method of mRNA test combined with L1 methylation assay, we obtained a sensitivity of 89.8% and a specificity of 71.9%. These findings suggest that assessment of HPV-16 L1 methylation testing combined with E6/E7 mRNA testing may be a promising method for the triage of women with HPV type 16 only. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening

    Science.gov (United States)

    Geng, Li; Feng, Jiantao; Sun, Quanmei; Liu, Jing; Hua, Wenda; Li, Jing; Ao, Zhuo; You, Ke; Guo, Yanli; Liao, Fulong; Zhang, Youyi; Guo, Hongyan; Han, Jinsong; Xiong, Guangwu; Zhang, Lufang; Han, Dong

    2015-09-01

    Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03662c

  2. The management of cervical intra-epithelial neoplasia (CIN): Extensiveness and costs in The Netherlands

    NARCIS (Netherlands)

    M. van Ballegooijen (Marjolein); M.A. Koopmanschap (Marc); J.D.F. Habbema (Dik)

    1995-01-01

    textabstractIn order to provide greater insight into both the extensiveness and the medical costs of the diagnosis and treatment of screen-detected cervical intra-epithelial neoplasia (CIN) in general medical practice in The Netherlands, data from national registries and gynaecology departments were

  3. Natural history of high-grade cervical intraepithelial neoplasia : a review of prognostic biomarkers

    NARCIS (Netherlands)

    Koeneman, Margot M.; Kruitwagen, Roy F. P. M.; Nijman, Hans W.; Slangen, Brigitte F. M.; Van Gorp, Toon; Kruse, Arnold-Jan

    The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical

  4. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    Marcelino Hernandez Valencia

    2011-11-01

    Full Text Available Human papilloma virus (HPV can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA has shown fewer side effects and its systemic use makes it possible to reach difficultto- treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL. Subjects began treatment based on GA using two routes of administration - systemic (oral and topical (spray - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap smear. Simple statistics were used along with two-tailed Student’s t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74% (P<0.001. However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL, treatment may be required for a longer period as with other drugs used

  5. Mild obesity, physical activity, calorie intake, and the risks of cervical intraepithelial neoplasia and cervical cancer.

    Directory of Open Access Journals (Sweden)

    Jae Kwan Lee

    Full Text Available OBJECTIVE: We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN and cervical cancer. METHODS: We enrolled 1125 women (age, 18-65 years into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs and the corresponding 95% confidence intervals (95% CIs, and to assess whether body mass index (BMI, height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. RESULTS: Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5-23 kg/m(2, the multivariate ORs (95% CIs for those overweight (23-25 kg/m(2 and mild obesity (≥25 kg/m(2 were 1.25 (0.79-2.00 and 1.70 (1.10-2.63, respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week, the ORs (95% CIs for cervical cancer were 0.95 (0.61-1.48 and 0.61 (0.38-0.98 for women with medium physical activity (38.5-71.9 MET-hours/week and those with high physical activity (72 MET-hours/week, respectively (p for linear trend  = 0.03. The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week, the ORs (95% CIs for CIN2/3 were 0.64 (0.40-1.01 and 0.58 (0.36-0.93 for the medium and high physical activity groups, respectively (p for linear trend  = 0.02. Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. CONCLUSION: Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy

  6. 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

  7. High frequency of loss of heterozygosity in vulval intraepithelial neoplasia (VIN) is associated with invasive vulval squamous cell carcinoma (VSCC)

    NARCIS (Netherlands)

    B.P.L. Wijnhoven (Bas); E.W. Lindstedt (Eric); M. Abbou; Y. Ijzendoorn (Ynske); R.R. de Krijger (Ronald); H.W. Tilanus (Hugo); W.N.M. Dinjens (Winand)

    2001-01-01

    textabstractVulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in

  8. The immunomorphological features of cervical intraepithelial neoplasia associated with HPV infection depending on the type of infertility

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    Е. О. Kindrativ

    2016-12-01

    Full Text Available Aim. Objective was to establish the features of markers expression of receptivity, proliferation, apoptosis and angiogenesis of cervix with CIN associated with HPV infection in various forms of female infertility. Materials and methods. Cervical biopsy material of 157 women with CIN associated with HPV infection in infertility was investigated. Depending on the degree of CIN all cases are divided into three groups: 1st group – 62 women with mild CIN (CIN-I, 2nd group – 53 women with moderate CIN (CIN-II, 3rd group – 42 patients with severe CIN (CIN-III. The control group consisted of 15 cervical samples from infertile women without cervical pathology. For immunohistochemical (IHC studies the primary monoclonal antibodies Ki-67 (Clone MIB-1, DakoCytomation r63 (clone 4A4, DakoCytomation, VEGF (clone VG1, DakoCytomation, p16ink4a (kit for histological preparations, number K5334, estrogen (ER (clone 6F11, Novocastra and progesterone receptors (PR (clone 1A6, Novocastra were used. Results. As a result of studies it was found that dysplastic cervical processes in terms of human papilloma virus infection are characterized by severe structural changes in the form of cell renewal violation, redistribution of hormonal reception and expression of vascular endothelial growth factor by stratified squamous epithelium especially in the tubular, hormonal and combined infertility. Conclusions. It was established that for infertility the cervical intraepithelial neoplasia (CIN associated with HPV infection (PVI is characterized by different individual potential for the development of cervical carcinoma. For early detection, verification of the severity degree and prognosis of CIN, especially during the tubular, hormonal and combined forms of infertility it is advisable to include the immunomorphological study of tissue of the cervix using monoclonal antibodies (Ki-67, r63, pl6ink4a, ER, PR, VEGF in the algorithm of complex inspection.

  9. The association of HPV genotype with the regression, persistence or progression of low-grade squamous intraepithelial lesions.

    Science.gov (United States)

    Silveira, F A; Almeida, G; Furtado, Y L; Cavalcanti, S; Silva, K S; Maldonado, P; Carvalho, M G C

    2015-12-01

    Human papillomavirus (HPV) is a highly prevalent sexually transmitted virus causing cytological alterations that precede cervical cancer. Approximately 130 genotypes have been sequenced. Low-grade squamous intraepithelial lesions (LSIL) are the most frequent cytological alteration and have an uncertain behavior. To analyze the frequency of HPV types in LSIL and their association with the regression, persistence or progression of these lesions. A cohort study of forty patients with LSIL cytology was conducted from December 2007 to March 2011. The follow-up lasted two years and included cytology and colposcopy. HPV detection was performed using PCR, and genotyping was performed using PCR-specific and RFLP techniques. DNA-HPV was detected in 87% (35/40) of the cases, with oncogenic HPV accounting for 76%; type 16 in 32% (11/35) and type 18 in 20%. LSIL regression, persistence and progression rates at the end of the study were 60%, 23% and 17%, respectively. There was 50% regression in lesions in the high oncogenic risk group (types 16 and 18). HPV 16 was the most frequent genotype found in LSIL. The persistence and progression of the LSIL were related to the persistence of oncogenic HPV. The longer the follow-up time, the lower the LSIL persistence rate and the higher its regression rate; the progression rate remained stable. In addition to the presence of oncogenic HPV, other factors are necessary for the progression of LSIL. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Spectrum of HPV types before and after treatment of cervical intraepithelial neoplasia grade 2 and 3.

    Science.gov (United States)

    Lindroth, Ylva; Bjelkenkrantz, Kaj; Forslund, Ola

    2017-10-31

    To monitor residual disease after treatment of high grade cervical intraepithelial neoplasia (CIN), cytology together with human papillomavirus (HPV) testing are commonly performed. To analyse the spectrum of HPV types before and after treatment. This register-based study included 446 women treated for CIN2 or 3, where cytology samples had been HPV-tested before and after treatment by the use of the MGP-PCR Luminex HPV L1-DNA-assay identifying 39 HPV types, including 12 high risk (HR) HPV types. Before and after treatment, 706 and 248 HPV isolates were detected of 36 and 34 different HPV types, respectively. Among all the HR HPV isolates, type-specific persistency was observed among 14% (76/542) after treatment, compared to 34% (31/92) of low-risk (LR) HPV isolates (pHPV isolates, 8.3% (6/72) persisted. Totally, 99% (440/446) and 40% (179/446) of the women were HPV-positive before and after treatment, respectively. At least one of the 12 HR HPV types was present in 91% (404/446) and 24% (109/446) of the women before and after treatment, respectively (pHPV types were present both before and after treatment among 23% (102/446) of the women, and 16% (71/446) manifested at least one persistent HR HPV type. The sensitivity, specificity and negative predictive value of HR HPV testing for detection of residual high grade squamous intraepithelial lesion (HSIL) was based on the first cytology after treatment, and was 91.7% (95% CI: 61.5%-99.8%), 84.1% (95% CI: 80.0%-87.7%) and 99.7% (95% CI: 98.2%-100.0%), respectively. About one out six treated women (16%) manifested at least one persistent HR HPV type, that was associated with recurrent or residual HSIL disease (odds ratio 58.1, 95% CI 7.4-457) (p=0.0001). Testing for HR HPV demonstrated high sensitivity (92%) for residual HSIL. The higher persistency rate of LR HPV types suggests that they are more likely to be outside the treated area. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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 HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested 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

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

    African Journals Online (AJOL)

    The study population constituted of HIV positive women attending the ART treatment clinic. A total of 715 HIV positive women initiated on Antiretroviral Therapy (ART) were enrolled in this study. About 359 (52.1%) were less than 40 years of age and 644 (90.3%) of the patients were widowed. About 642 (92.6%) of the HIV ...

  13. Risk Factors Associated With Cervical Intraepithelial Lesions In A ...

    African Journals Online (AJOL)

    Context Cervical cancer despite being largely preventable, is still the leading cause of gynaecological cancer related death among females in developing countries. Identification of risk factors will help to reduce the morbidity and mortality associated with cervical cancer. Methodology This was a prospective study involving ...

  14. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    Cerasuolo, Andrea; Annunziata, Clorinda; Tortora, Marianna; Starita, Noemy; Stellato, Giovanni; Greggi, Stefano; Maglione, Maria Grazia; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M.; Tornesello, Maria Lina

    2017-01-01

    Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC, along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell) compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression pattern showed statistically significant higher levels of E6*I versus E6*II isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal SCC suggesting different carcinogenic mechanisms in the two types of HPV-related cancers. PMID:28423662

  15. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Cerasuolo, Andrea; Annunziata, Clorinda; Tortora, Marianna; Starita, Noemy; Stellato, Giovanni; Greggi, Stefano; Maglione, Maria Grazia; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2017-05-23

    Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of a fraction of oropharyngeal carcinoma. Few studies compared the viral expression profiles in the two types of tumor. We analyzed HPV genotypes and viral load as well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC, along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell) compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression pattern showed statistically significant higher levels of E6*I versus E6*II isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal SCC suggesting different carcinogenic mechanisms in the two types of HPV-related cancers.

  16. [Application of SELDI-TOF serum proteome profiling in cervical squamous cell carcinoma].

    Science.gov (United States)

    Xia, Ting; Zheng, Zhi-Guo; Gao, Yun; Mou, Han-Zhou; Xu, Shen-Hua; Zhang, Ping; Zhu, Jian-Qing

    2008-03-01

    Up to now, there is no valid biomarker in early diagnosis of cervical cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a new technique used to identify biomarkers for cancers. This study was to screen new biomarkers and build diagnostic models for early diagnosis of cervical cancer by SELDI-TOF-MS. SELDI-TOF-MS was used to detect the serum proteomic patterns of 91 patients with early stage cervical squamous cell carcinoma, 15 patients with cervical intraepithelial neoplasia III (CIN III), and 55 healthy women (control). The serum proteomic spectra were generated on weak cation exchange (WCX2) chips. Differences in protein peaks were analyzed using Biomarker Wizard software. The diagnostic model was built by Biomarker Patterns software and further valuated by a large-scale blind test. A total of 122 protein peaks were detected at the molecular range of 1.5 to 20 ku, among which 19 ones were significantly different between invasive cervical squamous cell carcinomas and controls (P<0.001). A diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z was established. Its specificity was 83.78% (31/37) and its sensitivity was 97.29% (36/37). A sensitivity of 94.44% (51/54) and a specificity of 94.44% (17/18) in a large-scale blind test were obtained. The diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z can discriminate cervical cancer patients from healthy women.

  17. 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.

  18. Punch biopsy guided by both colposcopy and HR-HPV status is more efficient for identification of immediate high-grade squamous intraepithelial lesion or worse among HPV-infected women with atypical squamous cells of undetermined significance.

    Science.gov (United States)

    Ding, Z; Li, Y; Chen, A; Song, M; Zhang, Y

    2016-12-01

    To investigate the accuracy of colposcopy for diagnosing high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) in human papillomavirus (HPV)-infected patients with atypical squamous cells of undetermined significance (ASCUS) cytology, and determine whether genotyping and viral load quantitation can be useful for detecting immediate HSIL+ risk in these patients. This study included 620 cases with ASCUS and positive for high-risk (HR)-HPV within 1 month before or after cervical cytology at Qilu Hospital between February 2013 and February 2014. Based on the colposcopic impression, lesion-targeted punch biopsy, endocervical curettage biopsy or random cervical punch biopsy in four quadrants was performed on these patients within 1 month. The accuracy of colposcopy for diagnosing HSIL+ was evaluated through comparison with the biopsy results. HR-HPV status determined by Hybrid Capture 2 or HPV genotyping was analysed retrospectively as a possible predictor of HSIL+. Agreement between colposcopic impression and cervical pathology was matched perfectly in 89.2% of cases (553/620), and the strength of agreement with the κ statistic was 0.698 (ptypes of HPV (17.9%, pbiopsies considering HPV-16 infection or virus load ≥50 RLU/CO may be helpful for increasing the HSIL+ detection rate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. 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 cer......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...

  20. Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Barken, Sidsel S; Lynge, Elsebeth; Andersen, Erik S.

    2013-01-01

    OBJECTIVE: To measure adherence to annual follow-up among women treated for cervical intraepithelial neoplasia. DESIGN: Prospective, population-based, register study. SETTING: Denmark, 1996-2007. POPULATION: All women treated for cervical intraepithelial neoplasia with conization. METHODS: Treated...... the recommended follow-up. We measured this cumulative proportion conservatively in 15-month intervals for 5 years. RESULTS: Adherence to annual follow-up among 45 984 treated women decreased gradually. In total, 90% of these women obtained at least one smear in the first post-treatment year, but only 40......% obtained the recommended tests for 5 years. Five-year adherence was substantially better outside the capital area, for example, the odds ratio for women from Jutland compared with women from the capital area was 1.70 (95% confidence interval 1.60-1.82). CONCLUSIONS: Adherence to follow-up after conization...

  1. [Association of Chlamydia trachomatis and human papilloma virus as predisposing factors in cervical intraepithelial neoplasia].

    Science.gov (United States)

    González Sánchez, J L; Flores Avilés, Y; Gómez Campos, G; Montero Ramírez, A

    1995-10-01

    Human papilloma virus (HPV) has a predisposing association as cofactor in etiopathology of cervicouterine cancer; it is known also that viral infection is not enough, and there are other agents, as Chlamydia trachomatis. The objective of this study was to investigate the association of these cofactors as predisposal for intraepithelial cervical neoplasia (NIC). Prospectively, at Clinica de Colposcopia, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala", IMSS, 37 patients with cytologic, colposcopic and histological diagnosis of CIN pure or associated to HPV, underwent endocervical cytologies, and by immunofluorescence method, using monoclonal antibodies of conjugated fluoresceine, it was tried to demonstrate Chlamydia trachomatis, presence. From all patients, 12(32,4) were positive for Chlamydia trachomatis, significant percentually, and with Xi square of 0.32, non significant for this group of population. It is concluded that there is an important association of Chlamydia trachomatis and HPV, which should be taken into consideration in diagnosis and treatment of intraepithelial cervical neoplasia.

  2. Prevalence of high-risk human papillomavirus types in Mexican women with cervical intraepithelial neoplasia and invasive carcinoma

    Directory of Open Access Journals (Sweden)

    Sánchez-Garza Mireya

    2008-02-01

    Full Text Available Abstract Background Prevalence of high risk (HR human papillomavirus (HPV types in the states of San Luis Potosí (SLP and Guanajuato (Gto, Mexico, was determined by restriction fragment length-polymorphism (RFLP analysis on the E6 ~250 bp (E6-250 HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto. Fresh cervical scrapings for HPV detection and typing were obtained from all of them and cytological and/or histological diagnoses were performed on 383. Results Low grade intraepithelial squamous lesions (LSIL were diagnosed in 280 cases (73.1%, high grade intraepithelial squamous lesions (HSIL in 64 cases (16.7% and invasive carcinoma in 39 cases (10.2%. In the 437 cervical scrapings containing amplifiable DNA, only four (0.9% were not infected by HPV, whereas 402 (92.0% were infected HR-HPV and 31 (7.1% by low-risk HPV. RFLP analysis of the amplifiable samples identified infections by one HR-HPV type in 71.4%, by two types in 25.9% and by three types in 2.7%. The overall prevalence of HR-HPV types was, in descending order: 16 (53.4% > 31 (15.6% > 18 (8.9% > 35 (5.6 > 52 (5.4% > 33 (1.2% > 58 (0.7% = unidentified types (0.7%; in double infections (type 58 absent in Gto it was 16 (88.5% > 31 (57.7% > 35 (19.2% > 18 (16.3% = 52 (16.3% > 33 (2.8% = 58 (2.8% > unidentified types (1.0%; in triple infections (types 33 and 58 absent in both states it was 16 (100.0% > 35 (54.5% > 31 (45.5% = 52 (45.5% > 18 (27.3%. Overall frequency of cervical lesions was LSIL (73.1% > HSIL (16.7% > invasive cancer (10.2%. The ratio of single to multiple infections was inversely proportional to the severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types in HSIL and invasive cancer lesions was 16 (55.0% > 31 (18.6% > 35 (7.9% > 52 (7.1% > 18 (4.3% > unidentified types (3.6% > 33 (2.9% > 58 (0.7%. Conclusion Ninety

  3. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    OpenAIRE

    Levi, José E.; Fink, Maria C.S.; Canto, Cynthia L.M.; Carretiero, Nadily; Matsubara, Regina; Linhares, Iara; Dores, Gérson B. das; Castelo, Adauto; Segurado, Aluísio; Uip, David E.; Eluf Neto, José

    2002-01-01

    HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%). Twenty (7.5%) women were infected by one or more low-risk viruses, 89 (33%...

  4. Risk of preterm birth in women with cervical intraepithelial neoplasia grade one: a population-based cohort study.

    Science.gov (United States)

    Heinonen, Annu; Gissler, Mika; Paavonen, Jorma; Tapper, Anna-Maija; Jakobsson, Maija

    2018-02-01

    In this population-based register study our objective was to explore the association of cervical intraepithelial neoplasia, grade 1 and loop electrosurcigal excision procedure with preterm birth. Our population consisted of 4759 women diagnosed with cervical intraepithelial neoplasia, grade 1 during 1997-2009 and their 3021 subsequent deliveries analyzed by loop electrosurcigal excision procedure and parity. Hospital Discharge Register was used to identify women diagnosed for cervical intraepithelial neoplasia, grade 1 and these data were linked with the Medical Birth Register data. We calculated odds ratios with 95% confidence intervals. Cervical intraepithelial neoplasia, grade 1 patients with loop electrosurcigal excision procedure had 54 (6.7%) subsequent preterm births and the corresponding figure among cervical intraepithelial neoplasia, grade 1 patients without loop electrosurcigal excision procedure was 116 (5.2%). This results in odds ratios 1.31 (95% confidence interval 0.94-1.83). We assessed the risk before and after diagnosis of cervical intraepithelial neoplasia, grade 1 both for patients with loop electrosurcigal excision procedure (odds ratios 1.47, 95% confidence interval 1.05-2.06) and without loop electrosurcigal excision procedure (odds ratios 0.90, 95% confidence interval 0.71-1.13). An increased risk for preterm birth after diagnosis of cervical intraepithelial neoplasia, grade 1 and loop electrosurcigal excision procedure was observed. We also compared both groups to the background population in the Medical Birth Register. For cervical intraepithelial neoplasia, grade 1 patients without loop electrosurcigal excision procedure the risk for preterm birth was not increased (odds ratios 0.95, 95% confidence interval 0.76-1.21) whereas for cervical intraepithelial neoplasia, grade 1 patients treated with loop electrosurcigal excision procedure the risk for preterm birth was increased (odds ratios 1.45, 95% confidence interval 1.02-1.92). Loop

  5. Balance of apoptotic and anti-apoptotic marker and perforin granule release in squamous intraepithelial lesions. HIV infection leads to a decrease in perforin degranulation.

    Science.gov (United States)

    Fernandes, Ana Teresa G; da Rocha, Natalia Pereira; Avvad, Elyzabeth; Grinsztejn, Beatriz J; Russomano, Fabio; Tristão, Aparecida; Quintana, Marcel de Souza Borges; Perez, Mauricio A; Conceição-Silva, Fátima; Bonecini-Almeida, Maria da Gloria

    2013-10-01

    Cell-mediated cytotoxicity plays an important role in the regulation to HPV-associated cervical intraepithelial neoplasia. HIV co-infection is related to poorer prognosis and more rapid clinical progression to cancer. We evaluated the presence of cervical inflammatory cells, apoptotic (Bax, Bcl-2, FasL, NOS2, perforin) markers and the degranulating expressing cell marker (CD107a) in low and high squamous intraepithelial lesions (LSIL and HSIL, respectively) from HIV-negative and -positive women. Higher percentage of cervical CD4(+), CD8(+) T cells and macrophage were observed in LSIL and HSIL groups when compared with control, especially in epithelium and basal layer of epithelium. However, progression from LSIL to HSIL did not change the frequency of inflammatory cells. HIV-infection lead to a reduction on cervical CD4(+) T cell infiltration and an increased CD8(+) T cell distribution in LSIL groups. A balance between pro- and anti-apoptotic protein expressions was verified. Bax-expressing cells were present in all groups and were rarely expressed in keratinocytes in the epithelium in LSIL and control groups, but notably decreased in HSIL group. However, its frequency was enhanced in the basal layer of the epithelium meanly in LSIL group. Bcl2-expressing cells in the epithelium and the stroma were enhanced in HSIL group when compared with LSIL group. HIV-infection did not interfere in both expressions NOS2 expression was located on keratinocytes in both LSIL and HSIL groups when compared with control group. There were few FasL cervical expressing cells in all groups. Indeed, perforin was identified in few cervical cells. However, CD107a, a surface marker for cellular degranulation was significantly higher in epithelium, basal layer of epithelium and stroma in LSIL and HSIL, respectively, when compared with control group. These results support that HIV infection may induce reduction on inflammatory cervical cell degranulation corroborating to carcinogenesis process

  6. 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...

  7. The Analysis of Genetic Polymorphism. The Relationship between Interleukin – 4 Polymorphisms and Intraepithelial Cervical Neoplasia

    Directory of Open Access Journals (Sweden)

    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.

  8. Risk factors of cervical intraepithelial lesion in Douala-Cameroon ...

    African Journals Online (AJOL)

    Infection with high risk oncogenic human papillomavirus (HPV) such as HPVs 16 and 18 is the main cause of cervical cancer. The objective of this study was to determine the impact of Chlamydia trachomatis, Herpes simplex virus 2 (HSV 2), Treponema pallidum and some sexual behaviour on malignant progression of ...

  9. High-Grade Squamous Intraepithelial Lesion Cytology With Negative High-Risk Human Papillomavirus Tests Rarely Diagnoses Endometrial Cancer.

    Science.gov (United States)

    Pretorius, Robert G; Peterson, Patricia

    2015-07-01

    We hypothesized that women with cervical cytologic results of high-grade squamous intraepithelial lesion (HSIL) and negative high-risk human papillomavirus (HR-HPV) test results would have a high risk of having endometrial cancer and would benefit from routine endometrial biopsy. Reports of women with cytologic results of HSIL and negative HR-HPV test results were found in an electronic colposcopy database; their charts were reviewed. Rates of endometrial cancer for cytologic results of HSIL and negative HR-HPV test results were compared to a historical series for cytologic results of HSIL with positive HR-HPV and cytologic results of atypical glandular cells (AGCs) and negative HR-HPV test results. Between August 10, 1998, and April 20, 2013, 56 women were evaluated in our colposcopy clinics for cytologic results of HSIL and negative HR-HPV test results; of these 56 women, 1 (1.8%) was diagnosed with endometrial cancer. No endometrial cancer was diagnosed during the follow-up (median = 63 mo) after colposcopy. The risk for endometrial cancer with cytologic results of HSIL and negative HR-HPV test results (1.8%, 1/56) did not differ from that of a historical series from 2007 to 2009 from the same colposcopy clinic in 223 women with cytologic results of HSIL and positive HR-HPV test results (0.0%, 0/223; p = .2) and was lower than the risk for endometrial cancer from the historical series from 2007 to 2009 in women with cytologic results of AGC and negative HR-HPV test results (14.4%, 4/27; p = .04). Women with cytologic results of HSIL and negative HR-HPV test results are more like those with cytologic results of HSIL and positive HR-HPV test results than those with cytologic results of AGC and negative HR-HPV test results and would unlikely to benefit from routine endometrial biopsy at the time of colposcopy.

  10. Co-infections associated with human immunodeficiency virus type 1 in pregnant women from southern Brazil: high rate of intraepithelial cervical lesions

    Directory of Open Access Journals (Sweden)

    Michele Tornatore

    2012-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-positive pregnant women require specific prophylactic and therapeutic approaches. The efficacy of established approaches is further challenged by co-infection with other sexually transmitted diseases (STDs. The objective of this study was to determine the prevalence of co-infections in pregnant women infected with different HIV-1 subtypes and to relate these findings, together with additional demographic and clinical parameters, to maternal and infant outcomes. Blood samples from pregnant women were collected and tested for syphilis, hepatitis B virus (HBV and hepatitis C virus (HCV. Human papillomavirus (HPV diagnosis was evaluated by the presence of alterations in the cervical epithelium detected through a cytopathological exam. Medical charts provided patient data for the mothers and children. Statistical analyses were conducted with STATA 9.0. We found a prevalence of 10.8% for HCV, 2.3% for chronic HBV, 3.1% for syphilis and 40.8% for HPV. Of those co-infected with HPV, 52.9% presented high-grade intraepithelial lesions or in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores were similar between co-infected and non-co-infected women. The presence of other STDs did not impact maternal and concept outcomes. More than half of the patients presenting cervical cytology abnormalities suggestive of HPV had high-grade squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate of these lesions.

  11. Chlamydia trachomatis and risk of cervical intraepithelial neoplasia grade 3 or worse in women with persistent human papillomavirus infection

    DEFF Research Database (Denmark)

    Jensen, Kirsten E; Thomsen, Louise T; Schmiedel, Sven

    2014-01-01

    Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithel...... intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection....

  12. Less medical intervention after sharp demarcation of grade 1-2 cervical intraepithelial neoplasia smears by neural network screening

    NARCIS (Netherlands)

    Kok, MR; Boon, ME; Schreiner-Kok, PG; Hermans, J; Grobbee, DE; Kok, LP

    2001-01-01

    BACKGROUND. Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS. Of 133,196 women who were

  13. HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3.

    NARCIS (Netherlands)

    Zielinski, G.D.; Rozendaal, L.; Voorhorst, F.J.; Berkhof, J.; Snijders, P.J.F.; Risse, E.K.J.; Runsink, AP; Schipper, de FA; Meijer, C.J.L.M.

    2003-01-01

    OBJECTIVE: We evaluated high-risk human papillomavirus (HPV) testing by Hybrid Capture II (HC II) in addition to cytology to predict recurrent/residual cervical intraepithelial neoplasia (CIN) 2/3 and cervical cancer in women treated for CIN 3. METHODS: Follow-up study of 108 women with

  14. The risk of preterm birth of treated versus untreated cervical intraepithelial neoplasia (CIN): a systematic review and meta-analysis

    NARCIS (Netherlands)

    Danhof, Nora A.; Kamphuis, Esme I.; Limpens, Jacqueline; van Lonkhuijzen, Luc R. C. W.; Pajkrt, Eva; Mol, Ben W. J.

    2015-01-01

    Cervical surgery is associated with preterm birth (PTB) and neonatal morbidity. However, it is unknown whether this increased risk is due to the surgery itself or to the cervical intraepithelial neoplasia (CIN) underlying the surgery. Our objective was to assess the risk for PTB in women with

  15. Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion specimens: a Japanese Gynecologic Oncology Group study.

    Science.gov (United States)

    Fujii, Takuma; Saito, Miyuki; Hasegawa, Toshihiko; Iwata, Takashi; Kuramoto, Hiroyuki; Kubushiro, Kaneyuki; Ohmura, Mineo; Ochiai, Kazunori; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Aoki, Daisuke

    2015-02-01

    p16(INK4a) immunohistochemistry has revealed a high rate of positivity in cervical intraepithelial neoplasia grade 2 (CIN2) and more severe conditions (CIN2+). The Lower Anogenital Squamous Terminology Standardization project proposed p16(INK4a) immunohistochemistry as an ancillary test for CIN. Immunocytochemistry involving dual staining for p16(INK4a) and Ki-67 in the triage of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) is reported to be useful in the identification of CIN2+. However, it is unclear whether p16(INK4a)/Ki-67 immunocytochemistry is of practical relevance for the triage of ASCUS and LSIL in the Japanese screening system. From 427 women fulfilling the eligibility criteria, 188 ASCUS and 239 LSIL specimens were analyzed. The accuracy of p16(INK4a)/Ki-67 immunocytochemistry and genotyping of high-risk human papillomaviruses (HPVs) in detecting CIN2+ were compared. p16(INK4a)/Ki-67 immunocytochemistry was positive in 33.5 % (63/188) of ASCUS, and 36.8 % (88/239) of LSIL specimens. The sensitivity and specificity of p16(INK4a)/Ki-67 immunocytochemistry was 87.3 % (95 % confidence interval 78.0-93.8 %) and 76.4 % (71.6-80.8 %), respectively. The positive and negative predictive values were 45.7 % (37.6-54.0 %) and 96.4 % (93.4-98.3 %), respectively; positive and negative likelihood ratios were 3.71 and 0.17, respectively. Using the McNemar test, p16(INK4a)/Ki-67 immunocytochemistry showed equivalent sensitivity but higher specificity than the HPV genotyping test Compared with high-risk HPV genotyping, p16(INK4a)/Ki-67 immunocytochemistry was a more accurate triage test for identifying CIN2+ in ASCUS and LSIL specimens.

  16. Risk factors for unrecognized invasive carcinoma in patients with vulvar high-grade squamous intraepithelial lesion at vulvoscopy-directed biopsy.

    Science.gov (United States)

    Preti, Mario; Bucchi, Lauro; Ghiringhello, Bruno; Privitera, Silvana; Frau, Valentina; Corvetto, Elisabetta; Benedetto, Chiara; Micheletti, Leonardo

    2017-07-01

    To evaluate the prevalence and risk factors for unrecognized invasive carcinoma in a series of patients undergoing surgical excision after an office biopsy of vulvar high-grade squamous intraepithelial lesion (VHSIL). Two hundred and sixteen consecutive patients treated in a tertiary-level referral center for vulvar disease in north-western Italy were recruited. Patients' records were reviewed by trained personnel. Factors showing a statistically significant (pbiopsy had associated cervical/vaginal intraepithelial neoplasia, and more than 35% had a multifocal lesion. Invasive carcinoma was detected in surgical specimens from 24 patients (11%). The depth of stromal invasion varied between 0.1 mm and 3.0 mm with a median of 0.5 mm. In multivariate analysis, the risk of invasive carcinoma detection was greater for patients in the highest tertile of age (p=0.008), for patients with a lesion ≥20 mm in size (p=0.013) and with clitoral involvement (pbiopsy are independently associated with the risk of unrecognized invasive carcinoma.

  17. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-11-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.

  18. 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

  19. Fraction of high-grade cervical intraepithelial lesions attributable to genotypes targeted by a nonavalent HPV vaccine in Galicia, Spain.

    Science.gov (United States)

    Perez, S; Iñarrea, A; Pérez-Tanoira, R; Gil, M; López-Díez, E; Valenzuela, O; Porto, M; Alberte-Lista, L; Peteiro-Cancelo, M A; Treinta, A; Carballo, R; Reboredo, M C; Alvarez-Argüelles, M E; Purriños, M J

    2017-11-06

    Human papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain). Cervical scrapings (2009-2014) of women with histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2, n = 145) and grade 3-carcinoma in situ (CIN3-CIS, n = 244) were tested with Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). Hierarchical estimation of the fraction attributable to HPV 16/18 or HPV 31/33/45/52/58 detected alone or in combination was calculated. Absolute additional fraction attributable to genotypes targeted by nonavalent vaccine compared to genotypes targeted by bi-quadrivalent vaccines was calculated as the increment of attributable cases with respect to all studied cases. Age group 1, 2 and 3 included women 18 to 34, 35-44 and ≥45 years old, respectively. EPIDAT 3.1 was used. Fraction attributable to genotypes targeted by bi-quadrivalent vaccines was 59% CIN2 vs. 69% CIN3-CIS (p < 0.001). It was 63/51/50% of CIN2 and 78/66/45% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by nonavalent vaccine was 86% CIN2 and 86% CIN3-CIS. It was 87/91/75% of CIN2 and 90/86/76% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by these vaccines tended to decrease as age increased (p-trend <0.05). Globally, absolute additional attributable fraction was 16%, 26% and 29% in age group 1, 2 and 3, respectively (p < 0.005). Absolute additional fraction of CIN2 and CIN3-CIS attributable to genotypes targeted by nonavalent vaccine was observed in women

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

    Science.gov (United States)

    Clavero, Omar; McCloskey, Jenny; Molina, Vicente Marco; Quirós, Beatriz; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, F Xavier; Pimenoff, Ville N

    2017-06-01

    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. 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. 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. 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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. [The role of HPV genotyping testing in follow-up of high grade squamous intraepithelial lesion after treatment].

    Science.gov (United States)

    Li, Ning; Zuo, Jing; Huang, Ying; An, Jusheng; Yao, Hongwen; Li, Xiaoguang; Zhang, Rong; Li, Bin; Zhang, Xun; Guo, Huiqin; Wu, Lingying

    2015-04-01

    To assess the clinical value of HPV genotyping in follow-up after treatment for cervical high grade squamous intraepithelial lesion (HSIL). Two hundred and thirty eight patients with HSIL receiving conization in Cancer Hospital, Chinese Academy of Medical Sciences from Dec, 2006 to Jan, 2009 were accrued in our study. All the patients were prospectively observed after conization every 6 months for 3 times or till histologically confirmed recurrence. The items in every visit included pelvic examination, cervical cytology and HPV genotyping. Twenty-one HPV genotypes were detected by PCR-hybridization method. The last follow-up was July 31, 2010, and the median follow-up time was 28.3 months (range 6.5-43.0 months). Kaplan-Meire method as used for analyzed the median recurrent time, and the relationships between HPV status and recurrent disease were calculated by and log-rank test and Cox-regression model. Among the 238 patients, 110 cases (46.2%, 110/238) had positive result of HPV DNA testing at any visit. The most common HPV types detected in follow-up were HPV16 (45.6%), HPV58 (26.5%), and HPV52 (16.9%). There was no correlation between recurrent disease and any individual high risk HPV infections (P>0.05). Seventeen recurrent cases (7.1%) were identified in 238 patients within a median recurrent time of 14.9 months (range 6.0-32.1 months). In univariate analyses, HPV positive at any visit, persistent infection, multiple infection, type specific persistent infection and positive HPV at 18 months after conization were indicators for residual/recurrent disease (PHPV infection (HR=8.6, 95% CI: 1.8-41.7, P=0.008) and type specific persistent HPV infection (HR=5.1, 95% CI: 1.0-24.8, P=0.042) had an elevated risk of recurrent disease. HSIL with multiple HPV infection and type specific persistent HPV infection in follow-up are at high risk of recurrent disease. Patients with HPV turning into negative within 18 months after treatment have a low risk of recurrence.

  2. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

    DEFF Research Database (Denmark)

    Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M

    2010-01-01

    To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....

  3. The prognostic significance of virus-associated changes in grade 1 cervical intra-epithelial neoplasia

    DEFF Research Database (Denmark)

    Bagi, P; Worning, A M; Nordsten, M

    1987-01-01

    Virus-associated changes of the cervix uteri were assessed in patients treated for grade 1 cervical intra-epithelial neoplasia (CIN). Of 106 patients evaluated, 67 (63%) had virus-associated changes. The patients were treated without regard to the presence/absence of virus-associated changes. In 26...... patients the treatment was unsuccessful (persistence, recurrence, or progression of the neoplasia). The frequency of treatment failure was 33% in patients with, and 10% in patients without virus-associated changes (p less than 0.025). It is recommended that patients with CIN 1 and virus-associated changes...

  4. Medical Devices; Hematology and Pathology Devices; Classification of a Cervical Intraepithelial Neoplasia Test System. Final order.

    Science.gov (United States)

    2018-01-03

    The Food and Drug Administration (FDA or we) is classifying the cervical intraepithelial neoplasia (CIN) test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the CIN test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  5. Association of Human Papillomavirus 31 DNA Load with Risk of Cervical Intraepithelial Neoplasia Grades 2 and 3.

    Science.gov (United States)

    Liu, Xia; Schiffman, Mark; Hulbert, Ayaka; He, Zhonghu; Shen, Zhenping; Koutsky, Laura A; Xi, Long Fu

    2015-11-01

    The association between human papillomavirus 31 (HPV31) DNA loads and the risk of cervical intraepithelial neoplasia grades 2 and 3 (CIN2-3) was evaluated among women enrolled in the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS), who were monitored semiannually over 2 years and who had HPV31 infections detected at ≥1 visit. HPV31 DNA loads in the first HPV31-positive samples and in a random set of the last positive samples from women with ≥2 HPV31-positive visits were measured by a real-time PCR assay. CIN2-3 was histologically confirmed at the same time as the first detection of HPV31 for 88 (16.6%) of 530 women. After adjustment for HPV31 lineages, coinfection with other oncogenic types, and the timing of the first positive detection, the odds ratio (OR) per 1-log-unit increase in viral loads for the risk of a concurrent diagnosis of CIN2-3 was 1.5 (95% confidence interval [CI], 1.2 to 1.9). Of 373 women without CIN2-3 at the first positive visit who had ≥1 later visit, 44 had subsequent diagnoses of CIN2-3. The initial viral loads were associated with CIN2-3 diagnosed within 6 months after the first positive visit (adjusted OR, 1.5 [95% CI, 1.0 to 2.4]) but were unrelated to CIN2-3 diagnosed later. For a random set of 49 women who were tested for viral loads at the first and last positive visits, changes in viral loads were upward and downward among women with and without follow-up CIN2-3 diagnoses, respectively, although the difference was not statistically significant. Results suggest that HPV31 DNA load levels at the first positive visit signal a short-term but not long-term risk of CIN2-3. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Invasive Stratified Mucin-producing Carcinoma and Stratified Mucin-producing Intraepithelial Lesion (SMILE): 15 Cases Presenting a Spectrum of Cervical Neoplasia With Description of a Distinctive Variant of Invasive Adenocarcinoma.

    Science.gov (United States)

    Lastra, Ricardo R; Park, Kay J; Schoolmeester, J Kenneth

    2016-02-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is a cervical intraepithelial lesion, distinct from conventional squamous or glandular counterparts, believed to arise from embryonic cells at the transformation zone by transdifferentiation during high-risk HPV-associated carcinogenesis. It is characterized by stratified, immature epithelial cells displaying varying quantities of intracytoplasmic mucin throughout the majority of the lesional epithelium. We identified a distinct form of invasive cervical carcinoma with morphologic features identical to those in SMILE, which we have termed "invasive stratified mucin-producing carcinoma." Fifteen cases from 15 patients (mean 36 y; range, 22 to 64 y) were retrieved from the pathology archives of multiple institutions with a diagnosis of either SMILE or invasive cervical carcinoma with a description or comment about the invasive tumor's resemblance to SMILE. Seven cases had solely intraepithelial disease with a component of SMILE (mean 29 y; range, 22 to 40 y). The 8 other cases had invasive stratified mucin-producing carcinoma (mean 44; range, 34 to 64 y) in which SMILE was identified in 7. All cases of invasive stratified mucin-producing carcinoma demonstrated stratified, immature nuclei with intracytoplasmic mucin, which morphologically varied between cases from "mucin-rich" to "mucin-poor" in a similar manner to SMILE. All cases had mitotic figures and apoptotic debris, and an intralesional neutrophilic infiltrate was seen in the majority of cases. In cases of invasive carcinoma, the depth of invasion ranged from <1 to 19 mm. Follow-up information was available in 8 cases and ranged from 1 to 36 months (mean 11 mo). Three cases of invasive stratified mucin-producing carcinoma had biopsy or resection-proven metastatic carcinoma on follow-up. These 15 cases of cervical stratified mucin-producing lesions show a combination of intraepithelial and invasive growth patterns. Given that SMILE is well rooted as a

  7. Association Between Passive Smoking and the Risk of Cervical Intraepithelial Neoplasia 1 in Korean Women.

    Science.gov (United States)

    Min, Kyung-Jin; Lee, Jae-Kwan; So, Kyeong A; Kim, Mi Kyung

    2018-01-05

    The role of passive smoking on cervical carcinogenesis remains controversial. We investigated the association of passive smoking with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. The study recruited 1,322 women, aged 18-65 with normal cytology (n = 592), CIN1 (n = 420), CIN2/3 (n = 165), and cervical cancer (n = 145) from 2006 to 2009. This study is a cross-sectional analysis using the baseline data from the Korean human papillomavirus (HPV) cohort study. Detailed information on smoking behaviors and lifestyles were collected using questionnaires. Multinomial logistic regression analysis was performed to estimate multivariable-adjusted odds ratios (ORs). Passive smoking was not statistically related to the risk of CINs and cervical cancer. However, passive smoking among non-smokers was associated with higher CIN 1 risk (OR 1.53; 95% confidence interval [CI], 1.07-2.18), compared to not passive smoking, after adjusting for demographic factors, lifestyles, and oncogenic-HPV infection status. CIN 1 risk increased with longer time exposed to passive smoking (P for trend passive smoking and that of ≥2 hours/day of passive smoking were 2.48 (95% CI, 1.49-4.14) and 2.28 (95% CI, 1.21-4.26) for CIN 1, compared to not passive smoking. This study found that passive smoking among non-smoking women is associated with the risk of CIN 1.

  8. 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

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

    Science.gov (United States)

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

    2017-01-01

    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 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.

  10. Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Nara Chartuni Pereira Teixeira

    Full Text Available OBJECTIVES: To evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN among HIV-infected women. METHODS: Cross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors. RESULTS: CIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1. Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5-10.1, with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2-3.5, and with age < 34 years old (OR 1.5, 95% CI 1.0-2.4. HIV viral load and antiretroviral use were not independent risk factors for CIN. CONCLUSIONS: Severity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.

  11. Hypermutation in the E2 gene of human papillomavirus type 16 in cervical intraepithelial neoplasia.

    Science.gov (United States)

    Kukimoto, Iwao; Mori, Seiichiro; Aoyama, Satoru; Wakae, Kousho; Muramatsu, Masamichi; Kondo, Kazunari

    2015-10-01

    Persistent infection with oncogenic human papillomavirus (HPV) causes cervical cancer. However, viral genetic changes during cervical carcinogenesis are not fully understood. Recent studies have revealed the presence of adenine/thymine-clustered hypermutation in the long control region of the HPV16 genome in cervical intraepithelial neoplasia (CIN) lesions, and suggested that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins, which play a key role in innate immunity against retroviral infection, potentially introduce such hypermutation. This study reports for the first time the detection of adenine/thymine-clustered hypermutation in the E2 gene of HPV16 isolated from clinical specimens with low- and high-grade CIN lesions (CIN1/3). Differential DNA denaturation PCR, which utilizes lower denaturation temperatures to selectively amplify adenine/thymine-rich DNA, identified clusters of adenine/thymine mutations in the E2 gene in 4 of 11 CIN1 (36.4%), and 6 of 27 CIN3 (22.2%) samples. Interestingly, the number of mutations per sample was higher in CIN3 than in CIN1. Although the relevance of E2 hypermutation in cervical carcinogenesis remains unclear, the observed hypermutation patterns strongly imply involvement of APOBEC3 proteins in editing the HPV16 genome during natural viral infection. © 2015 Wiley Periodicals, Inc.

  12. Human telomerase gene and high-risk human papillomavirus infection are related to cervical intraepithelial neoplasia.

    Science.gov (United States)

    Zhao, Xu-Ye; Cui, Yong; Jiang, Shu-Fang; Liu, Ke-Jun; Han, Hai-Qiong; Liu, Xiao-Su; Li, Yali

    2015-01-01

    Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

  13. Evidence supporting see-and-treat management of cervical intraepithelial neoplasia: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Ebisch, R.M.F.; Rovers, M.M.; Bosgraaf, R.P.; Pluijm-Schouten, H.W. van der; Melchers, W.J.; Akker, P.A.J. van den; Massuger, L.F.; Bekkers, R.L.M.

    2015-01-01

    BACKGROUND: Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. OBJECTIVES: To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of

  14. THE 3-GROUP METAPHASE AS A MORPHOLOGIC INDICATOR OF HIGH-PLOIDY CELLS IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    NARCIS (Netherlands)

    PIETERS, WJLM; KOUDSTAAL, J; PLOEMZAAYER, JJ; Janssens, J; OOSTERHUIS, JW

    There is a need for additional morphologic criteria to improve the value of histologic classification for the prediction of the biologic behavior of cervical intraepithelial neoplasia (CIN). Representative slides from 72 cone specimens containing CIN were examined to study the correlation between

  15. “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

  16. Induction of transforming growth factor beta-1 in cervical intraepithelial neoplasia in vivo after treatment with beta-carotene.

    Science.gov (United States)

    Comerci, J T; Runowicz, C D; Fields, A L; Romney, S L; Palan, P R; Kadish, A S; Goldberg, G L

    1997-02-01

    Transforming growth factor (TGF) beta1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-beta1 and/or loss of TGF-beta1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-beta1. Matched cervical biopsies taken from 10 patients before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-beta1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with beta-carotene (P = 0.003). These results demonstrate regulation of a TGF-beta isoform in vivo in humans in response to beta-carotene administered as a chemopreventive agent.

  17. Results of a control quality strategy in cervical cytology

    OpenAIRE

    Gullo, Caio Eduardo; Dami, Anna Luiza Tannús; Barbosa, Amanda Pires; Marques, Aline Maria de Vita; Palmejani, Marianna Angelo; Lima, Luiz Guilherme Cernaglia Aureliano de; Bonilha, Jane Lopes

    2012-01-01

    OBJECTIVE: To determine the efficacy of a quality control strategy in cervical cytology in the detection of high-grade squamous intraepithelial lesions. METHODS: Forty-two patients were selected who underwent a Pap smear and cervical uterine biopsy between April 2008 and December 2009, with evidence of a high-grade squamous intraepithelial lesion in one or both tests. The statistical parameters of the smear test were calculated before and after systematic meetings for review of the archived t...

  18. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

    Science.gov (United States)

    Siegenbeek van Heukelom, Matthijs L; Marra, Elske; de Vries, Henry J C; Schim van der Loeff, Maarten F; Prins, Jan M

    2017-10-23

    HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive MSM to develop more stringent screening criteria. We studied a cohort of MSM screened by high-resolution anoscopy at three HIV clinics in Amsterdam, the Netherlands. For every first high-resolution anoscopy performed in a patient, we analyzed five demographic and seven HIV-related potential risk factors for four different outcome measures: histologically proven anal HSIL vs. no squamous intraepithelial lesions (SIL), HSIL-anal intraepithelial neoplasia 2 vs. no SIL, HSIL-anal intraepithelial neoplasia 3 vs. no SIL, and HSIL vs. no HSIL. We used univariable and multilevel, multivariable logistic regression. From 2008 through 2015, 497 out of 1678 (30%) screened HIV-positive MSM had anal HSIL. The mean age was 49 years (SD 9.6), 96% used combination antiretroviral therapy, and median duration of combination antiretroviral therapy use was 7.8 years (interquartile range 4.0-12.4). Increasing age [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI) 0.70-0.94, P = 0.006] and years living with suppressed viral load [1-5 years suppressed aOR 0.52 (95% CI 0.34-0.80), 5.01-10 years aOR 0.47 (95% CI 0.29-0.74), >10 years aOR 0.54 [0.34-0.87], all compared to less than 1 year suppressed, P = 0.009] were found to be protective for HSIL vs. no SIL. Young HIV-positive MSM without viral suppression are statistically at highest risk for anal HSIL, but given the high prevalence among all virally suppressed men, we advise that all HIV-positive MSM should be screened for HSIL.

  19. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

    Science.gov (United States)

    Siegenbeek van Heukelom, Matthijs L.; Marra, Elske; de Vries, Henry J.C.; van der Loeff, Maarten F. Schim; Prins, Jan M.

    2017-01-01

    Objective: HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive MSM to develop more stringent screening criteria. Design: We studied a cohort of MSM screened by high-resolution anoscopy at three HIV clinics in Amsterdam, the Netherlands. Methods: For every first high-resolution anoscopy performed in a patient, we analyzed five demographic and seven HIV-related potential risk factors for four different outcome measures: histologically proven anal HSIL vs. no squamous intraepithelial lesions (SIL), HSIL-anal intraepithelial neoplasia 2 vs. no SIL, HSIL-anal intraepithelial neoplasia 3 vs. no SIL, and HSIL vs. no HSIL. We used univariable and multilevel, multivariable logistic regression. Results: From 2008 through 2015, 497 out of 1678 (30%) screened HIV-positive MSM had anal HSIL. The mean age was 49 years (SD 9.6), 96% used combination antiretroviral therapy, and median duration of combination antiretroviral therapy use was 7.8 years (interquartile range 4.0–12.4). Increasing age [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI) 0.70–0.94, P = 0.006] and years living with suppressed viral load [1–5 years suppressed aOR 0.52 (95% CI 0.34–0.80), 5.01–10 years aOR 0.47 (95% CI 0.29–0.74), >10 years aOR 0.54 [0.34–0.87], all compared to less than 1 year suppressed, P = 0.009] were found to be protective for HSIL vs. no SIL. Conclusion: Young HIV-positive MSM without viral suppression are statistically at highest risk for anal HSIL, but given the high prevalence among all virally suppressed men, we advise that all HIV-positive MSM should be screened for HSIL. PMID:28991027

  20. Gene promoter methylation patterns throughout the process of cervical carcinogenesis

    NARCIS (Netherlands)

    Yang, Nan; Nijhuis, Esther R.; Volders, Haukeline H.; Eijsink, Jasper J. H.; Lendvai, Agnes; Zhang, Bo; Hollema, Harry; Schuuring, Ed; Wisman, G. Bea A.; van der Zee, Ate G. J.

    2010-01-01

    Objectives: To determine methylation status of nine genes, previously described to be frequently methylated in cervical cancer, in squamous intraepithelial lesions (SIL). Methods: QMSP was performed in normal cervix, low-grade ( L) SIL, high-grade (H) SIL, adenocarcinomas and squamous cell cervical

  1. Detection of high-risk human papillomavirus using menstrual blood in women with high-grade squamous intraepithelial lesions or high-risk human papillomavirus infections: A pilot study.

    Science.gov (United States)

    Lee, Banghyun; Cho, Hye-Yon; Jeon, Kum Jin; Kim, Kidong; Lee, Jung Ryeol; Moon, Jung Joo; No, Jae Hong; Kim, Yong-Beom

    2016-03-01

    Few studies have reported that human papillomavirus (HPV) tests using menstrual blood (MB) may be a convenient and effective screening modality for cervical cancer. Therefore, we aimed to investigate the efficacy of detecting high-risk (HR)-HPV from MB in women with high-grade squamous intraepithelial lesions or HR-HPV infections dependent on menstrual days. In this prospective exploratory pilot study, a clinical trial was conducted in 19 women. On enrollment into the study, gynecologists collected cervical cells. On the first and second day of menstruation, MB was self-collected by patients using a sanitary pad with a filter. The distribution of HPVs from MB and the accuracy of menstrual HR-HPV tests were evaluated using HPV genotyping. The agreement rate of detecting HR-HPVs using cervical and MB samples was also investigated. The sensitivity, specificity, positive and negative predictive values of the MB HR-HPV test for detecting cervical intraepithelial neoplasia (CIN) 3 or worse were 87.5%, 45.5%, 53.8%, and 83.3%, respectively, during both menstrual cycle day (MCD) 1 and 2 and MCD 1 only; and 62.5%, 27.3%, 38.5%, and 50.0%, respectively, during MCD 2 only. For CIN 3 or worse, the agreement rate between positive cervical and MB HR-HPV test results was 87.5% during MCD 1 and 62.5% during MCD 2. We demonstrated the possibility of using the MB HPV test as a screening modality for cervical cancer. © 2015 Japan Society of Obstetrics and Gynecology.

  2. Cervical intraepithelial lesions in females attending Women′s Health Clinics in Alexandria, Egypt

    Directory of Open Access Journals (Sweden)

    Mona Abdel-Hadi

    2015-01-01

    Full Text Available Background: Data from Egyptian studies provide widely varying estimates on the prevalence of preinvasive cervical lesions. The aim of this study was to estimate the rate of cervical intraepithelial neoplasia (CIN   in Egyptian women living in Alexandria to clarify the need for implementing a national organized screening program and a vaccination program in our community. Materials and Methods: The study was conducted over a 6 years period and covered the different socioeconomic levels to have a representative sample for women living in Alexandria. All women included did not have any cervical disorder related complaints. Conventional Pap smears were obtained and diagnosed using the Bethesda system. Women with abnormal Pap smears were managed according to the 2006 consensus guidelines within the available facilities. Persistent abnormal cytological results were referred for colposcopic biopsy. Histological results were grouped into: Reactive changes, CIN 1, CIN 2/CIN 3 and adenocarcinoma in-situ (AIS. Results: Out of the 6173 smears included in the study 6072 (98.36% were normal and only 101 (1.63% were abnormal. After colposcopic biopsies, 0.08% had CIN 1, 0.03% had CIN 2, 3 and 0.01% had AIS. Conclusion: We concluded that cervical cancer screening programs, although life-saving for a number of women, are not a sufficiently high priority in our community. Money for national health screening programs should preferably be directed more towards recruiting women for breast cancer screening, since breast cancer accounts for about 33% of all female cancers in Egypt ranking number one, while cervical cancer ranks number 13.

  3. Physicians' Awareness, Attitudes, and Experiences Regarding Imiquimod Treatment of Vaginal and Cervical Intraepithelial Neoplasia.

    Science.gov (United States)

    Koeneman, Margot M; van de Sande, Anna J M; van Beekhuizen, Heleen J; Gerestein, Kees G; van de Laar, Rafli; Kruitwagen, Roy F P M; Kruse, Arnold-Jan

    2016-01-01

    The aim of the study was to assess awareness, attitudes, and current clinical experiences of gynecologists regarding imiquimod as a potential treatment modality for vaginal intraepithelial neoplasia (VAIN) and cervical intraepithelial neoplasia (CIN). A 37-item questionnaire consisting of both multiple choice and open questions was sent to all Dutch gynecologists who regularly perform colposcopies in all 87 Dutch hospitals, in December 2014. The outcomes were assessed using descriptive statistics. Gynecologists from 52 hospitals (60%) completed the questionnaire. Of the 77 respondents, 79% and 58% were aware of imiquimod for treating VAIN and CIN, respectively. Twelve and 5 respondents had used imiquimod to treat VAIN and CIN, respectively; most treatments were for intractable VAIN lesions and recurrent lesions and to avoid surgical treatment for CIN in patients with a future pregnancy wish. Most respondents reported successful treatment outcomes but frequent adverse effects. Most (96%) stated that they would consider using imiquimod to treat high-grade CIN in selected patients, but only upon additional evidence and inclusion into treatment guidelines. The awareness of imiquimod as a potential treatment for VAIN and CIN was limited, possibly because of the paucity of evidence regarding vaginal imiquimod efficacy, the lack of inclusion into guidelines, and the high frequency of adverse effects. Imiquimod was applied off-label in a limited number of selected patients, with good treatment results. The respondents generally had a positive attitude toward treating VAIN and CIN with imiquimod. Additional evidence on treatment efficacy and inclusion in treatment guidelines is necessary before application in clinical practice.

  4. Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

    Science.gov (United States)

    Paraskevaidis, E; Koliopoulos, G; Malamou-Mitsi, V; Zikopoulos, K; Paschopoulos, M; Pappa, L; Agnantis, N J; Loli, D E

    2001-01-01

    Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

  5. Plasma Protein Profiles Differ Between Women Diagnosed with Cervical Intraepithelial Neoplasia (CIN 1 and 3

    Directory of Open Access Journals (Sweden)

    Edward E. Partridge

    2006-01-01

    Full Text Available Early detection of precancerous cells in the cervix and their clinical management is the main purpose of cervical cancer prevention and treatment programs. Cytological findings or testing for high risk (HR-human papillomavirus (HPV are inadequately sensitive for use in triage of women at high risk for cervical cancer. The current study is an exploratory study to identify candidate surface-enhanced laser desorption/ionization (SELDI time of flight (TOF mass spectrometry (MS protein profiles in plasma that may distinguish cervical intraepithelial neoplasia (CIN 3 from CIN 1 among women infected with HR-HPV. We evaluated the SELDI-TOF-MS plasma protein profiles of HR-HPV positive 32 women with CIN 3 (cases and 28 women with CIN1 (controls. Case-control status was kept blinded and triplicates of each sample and quality control plasma samples were randomized and after robotic sample preparations were run on WCX2 chips. After alignment of mass/charge (m-z values, an iterative method was used to develop a classifier on a training data set that had 28 cases and 22 controls. The classifier developed was used to classify the subjects in a test data set that has six cases and six controls. The classifier separated the cases from controls in the test set with 100% sensitivity and 100% specificity suggesting the possibility of using plasma SELDI protein profiles to identify women who are likely to have CIN 3 lesions.

  6. Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah

    2016-01-01

    Laboratories can nowadays choose from >100 Human Papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART and APTIMA, frequently do not detect...... intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women...... the younger age and more HPV infections. HPV test result discordance identified a cluster of low-risk HPV infections that were hardly ever associated with high-grade CIN and, almost exclusively, represented false-positive screening findings....

  7. Increased HIV-1 activity in anal high-grade squamous intraepithelial lesions compared with unaffected anal mucosa in men who have sex with men

    NARCIS (Netherlands)

    Pollakis, Georgios; Richel, Olivier; Vis, Joost D.; Prins, Jan M.; Paxton, William A.; de Vries, Henry J. C.

    2014-01-01

    We studied 3 patients with focal intra-anal tissue high-grade squamous intraepithelial lesions (HSILs). All had increased human immunodeficiency virus type 1 (HIV-1) RNA and DNA in lesions compared with that in healthy mucosa. HIV-1 RNA and HIV-1 episomal DNA were indicative of ongoing viral

  8. 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

    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. This

  9. 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

    -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...

  10. Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test

    NARCIS (Netherlands)

    Heijden, E.M. van der; Lopes, A.D.; Bryant, A.; Bekkers, R.L.M.; Galaal, K.

    2015-01-01

    BACKGROUND: Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer

  11. Cytology and human papillomavirus co-test results preceding incident high-grade cervical intraepithelial neoplasia.

    Directory of Open Access Journals (Sweden)

    Ina U Park

    Full Text Available High-risk HPV (hrHPV and cytology co-testing is utilized for primary cervical cancer screening and for enhanced follow-up of women who are hrHPV-positive, cytology negative. However, data are lacking on the utility of this method to detect pre-cancer or cancer in community-based clinical practice. This study describes cytology and hrHPV results preceding high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, or cervical cancer (i.e., CIN2+ in an integrated health system employing routine co-testing among women aged 30 years and older.We conducted a cross-sectional analysis of adult female members of Kaiser Permanente Northern California (KPNC with incident CIN2+ between July 2008 and June 2009. The primary outcome was the proportions of cytologic diagnoses and hrHPV co-test results preceding a diagnosis of CIN2+. Cervical cytology and hrHPV testing results were abstracted from electronic medical records.Of 1283 CIN2+ cases among adult women, 880 (68.5% were among women aged 30 years and older and 145/880 (16.5%, 95% CI 14.1-19.1 had only normal cytology during the 12 months prior to diagnosis. Furthermore, 133/880 (15.1%, 95% 12.9-17.7 were preceded by only normal cytology and persistent hrHPV infection (at least 2 positive hrHPV tests during the 6-36 months preceding CIN2+ diagnosis.Incident CIN2+ is frequently preceded by normal cytology and persistent hrHPV infection among women aged 30 years and older; screening strategies that employ HPV testing and cytology may improve the detection of CIN2+ compared with cytology alone.

  12. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis.

    Science.gov (United States)

    Kyrgiou, Maria; Mitra, Anita; Arbyn, Marc; Stasinou, Sofia Melina; Martin-Hirsch, Pierre; Bennett, Phillip; Paraskevaidis, Evangelos

    2014-10-28

    To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes. Systematic review and meta-analysis of cohort studies. Medline and Embase. Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint. Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I(2) statistics. 15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (Ptreatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16,558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women. There is no evidence suggesting that treatment for cervical intraepithelial neoplasia adversely affects fertility, although treatment was associated with a significantly increased risk of miscarriages in the second trimester. Research should explore mechanisms that may explain this increase in risk and stratify the impact that treatment may have on fertility and early pregnancy outcomes by the size of excision and treatment method used. © Kyrgiou et al 2014.

  13. 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.

  14. Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

    Science.gov (United States)

    Stentella, Patrizia; Biamonti, Alberto; Carraro, Carlo; Inghirami, Paolo; Mancino, Pasquale; Pietrangeli, Daniela; Votano, Sergio; Lazzari, Paola; DE Medici, Caterina

    2017-10-01

    Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl β-glucan (Colpofix®) gel as adjuvant therapy in HPV infection. The medical records of patients attending the Colposcopy Service of four hospitals in Rome from 2011 to 2013 were collected. Case arm consisted of patients submitted to local therapy with Colpofix®. Control arm comprised patients who did not receive this therapy. A total of 999 patients were included, divided into four groups, according to their cytological and histological specimens, colposcopy and subsequent management. Local therapy with Colpofix® gel resulted effective with respect to no therapy for the regression of low-grade CIN (CIN1) in patients submitted to follow up (P=0.0204), while it was no effective for the regression of CIN1 submitted to ablative therapy and high-grade CIN (CIN 2+) (P value not significant). In conclusion, Colpofix® gel represents a valid alternative to "wait and see" strategy in patients affected by CIN1. Further prospective studies are warranted to confirm these results.

  15. In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence

    Science.gov (United States)

    Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

    1994-10-01

    Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

  16. The use of cold coagulation for the treatment of cervical intraepithelial neoplasia

    LENUS (Irish Health Repository)

    Wyse, A

    2017-05-01

    In 2015, Cold Coagulation was introduced as a treatment for cervical intraepithelial neoplasia (CIN) at our colposcopy clinic. We reviewed the 6-month follow up data of the first 200 women who underwent Cold Coagulation using cytology and HPV status as tests of cure (TOC). A random sample of 200 patients treated by Large Loop Excision of the Transformation Zone (LLETZ) during the same period was used to compare treatment outcome. Six months following treatment,173 (86.5%) of the women treated by CC and 167 (83.5%) treated by LLETZ had negative cytology. (x2= P>0.05). 148 (74%) treated by Cold Coagulation and 166 (83%) treated by LLETZ were HPV negative (x2= P<0.05). One hundred and thirty-nine (70%) women treated by Cold Coagulation and 152 (76%) treated with LLETZ had normal cytology and were HPV negative. This audit of our initial experience supports the observation that Cold Coagulation is as effective as LLETZ in the management of CIN when cervical cytology is used as a test of cure.

  17. World Health Organization Guidelines: Use of cryotherapy for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Santesso, Nancy; Schünemann, Holger; Blumenthal, Paul; De Vuyst, Hugo; Gage, Julia; Garcia, Francisco; Jeronimo, Jose; Lu, Ricky; Luciani, Silvana; Quek, Swee C; Awad, Tahany; Broutet, Nathalie

    2012-08-01

    In 2008, cervical cancer was responsible for 275000 deaths, of which approximately 88% occurred in low- and middle-income countries. In 2009, the World Health Organization (WHO) committed to updating recommendations for use of cryotherapy for cervical intraepithelial neoplasia (CIN). We followed the WHO Handbook for Guidelines Development to develop present guidelines. An expert panel was established, which included clinicians, researchers, program directors, and methodologists. An independent group conducted systematic reviews and produced evidence summaries following the GRADE approach. GRADE evidence profiles were created for 16 key questions about the effects of cryotherapy in the presence of histologically confirmed CIN compared with no treatment and with loop electrosurgical excision procedure, as well as the use of different cryotherapy techniques. We identified a small number of randomized controlled trials or independently controlled observational studies. Surrogate outcomes were reported when evidence about outcomes critical to decision making were not available. The panel made 14 recommendations and documented factors that determined the strength and direction of the recommendations in decision tables. The present document summarizes new evidence-based WHO recommendations about the use of cryotherapy in women with histologically confirmed CIN for low-, middle-, and high-income countries. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

    Science.gov (United States)

    Ho, Gloria Y F; Einstein, Mark H; Romney, Seymour L; Kadish, Anna S; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D

    2011-10-01

    : This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

  19. 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

  20. Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.

    Science.gov (United States)

    Chang, Xiaohan; Zhang, Jing; Huang, Chenglin; Pang, Xiaoao; Luo, Qingshuang; Zhang, Huijie; Zhang, Shulan

    2015-09-01

    Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells SOX-2 expression (P SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.

  1. Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays.

    Science.gov (United States)

    Rebolj, Matejka; Bonde, Jesper; Preisler, Sarah; Ejegod, Ditte; Rygaard, Carsten; Lynge, Elsebeth

    2016-11-01

    Laboratories now can choose from >100 human papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART, and Aptima, frequently do not detect the same HPV infections. Here, we determined the characteristics of the concordant samples (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30 to 65 years of age (n = 2,859) and in a concurrent referral population from the same catchment area (n = 885). HPV testing followed the manufacturers' protocols. Women with abnormal cytology were managed according to the routine recommendations. Cytology-normal/HPV-positive women were invited for repeated testing in 18 months. Screening history and histologically confirmed cervical intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women with discordant samples. Additionally, assay signal strengths were substantially higher in concordant samples. More than 80% of ≥CIN2 results were found for women with concordant samples, and no ≥CIN2 results were found when the infection was detected by only one assay. These patterns were similar in the referral population despite the younger age and higher number of HPV infections. HPV test result discordance identified a cluster of low-risk HPV infections that were hardly ever associated with high-grade CIN and, almost exclusively, represented false-positive screening findings. Copyright © 2016 Rebolj et al.

  2. 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...... ability to control a persistent HPV infection. Impact: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer....

  3. 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.

  4. Viral and Cellular Biomarkers in the Diagnosis of Cervical Intraepithelial Neoplasia and Cancer

    Directory of Open Access Journals (Sweden)

    Maria Lina Tornesello

    2013-01-01

    Full Text Available Cervical cancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1 increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2 integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3 molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervical cancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervical cancer.

  5. 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...... could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types....

  6. Radiofrequency ablation for the endoscopic eradication of esophageal squamous high grade intraepithelial neoplasia and mucosal squamous cell carcinoma

    NARCIS (Netherlands)

    van Vilsteren, F. G.; Alvarez Herrero, L.; Pouw, R. E.; ten Kate, F. J.; Visser, M.; Seldenrijk, C. A.; van Berge Henegouwen, M. I.; Weusten, B. L.; Bergman, J. J.

    2011-01-01

    Background and study aims: Radiofrequency ablation (RFA) with or without prior endoscopic resection safely and effectively removes early neoplasia in Barrett's esophagus. We speculated that this approach might also be suited for early squamous neoplasia of the esophagus. The aim of the study was to

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  9. Detection of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cancer patients: Sharkia Governorate, Egypt.

    Science.gov (United States)

    Abd El-Azim, Shymaa; Lotfy, Mohamed; Omr, Ayman

    2011-01-01

    Cervical cancer (CCA) is the 2nd most common cancer among women worldwide. For approximately 2 years now, CCA has been converted from an oncological disease to an infectious disease, almost certainly caused by Human papillomavirus (HPV). Development of effective vaccines against the virus has created considerable issue world-wide and has major implications for both primary and secondary prevention strategies. The objective of this study was to establish the prevalence and genotype distribution of HPV in preinvasive, cervical intraepithelial neoplasia (CIN II and III) and invasive CCA in Sharkia governorate, Egypt. This study included 42 patients with CIN II and III, 30 patients with invasive CCA, and 45 controls who had undergone hysterectomy for any cause other than CCA. HPV detection and genotyping in cervical biopsies by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP). HPV DNA was detected in 85.7% (36/42) patients with CIN II and III. HPV genotypes were arranged in order of decreasing frequency as follows: HPV 16 being detected in 50.0% (21/42), HPV 45 in 143% (6/42) HPV 33 in 11.9% (5/42), HPV 18 in 9.5% (4/42) and HPV 31 in 7.1% (3/42) cases. In patients with invasive CCA, 93.3% (28/30) were positive for HPV DNA. In order of decreasing frequency, HPV genotypes were: HPV 16 being detected in 66.7% (20/30), HPV 18 in 16.7% (5/30), HPV 33 in 10.0% (3 /30) and both HPV 31 and HPV 45 in 6.7% (2/30) cases. About 13.3% invasive cervical cancer and 7.1% CIN II & III specimens exhibited multiple infections without significant difference (P > 0.05). HPV 16 and 33 infections show a higher risk for development of advanced stages of invasive CCA but without a statistically significant difference. The high prevalence of HPV genotypes 16, 18, and 45 in Sharkia governorate, Egypt, deserves attention as it has important implications for the usefulness of vaccine in prevention of a significant proportion of CCA and the choice of diagnostic

  10. Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

    DEFF Research Database (Denmark)

    Norling, Rikke; Buron, Birgitte Marie Due; Therkildsen, Marianne Hamilton

    2014-01-01

    INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US......) is a non-expensive, accessible and non-ionising imaging modality this method is not consistently used. This study aimed to investigate if addition of US of patients classified as clinically LN negative (cN0) by CT and/or MRI, increases the detection of LN metastases. Also, we aimed to identify which...... of the sonographic characteristics: echogenicity, border, shape, appearance of hilum and nodal blood-flow pattern best detect metastases in this patient group. METHOD: Fifty-one patients with OSCC classified as cN0 by CT/MRI were consecutively included and prospectively examined with US prior to sentinel node biopsy...

  11. Pretreatment serum squamous cell carcinoma antigen : A newly identified prognostic factor in early-stage cervical carcinoma

    NARCIS (Netherlands)

    Duk, JM; Groenier, KH; deBruijn, HWA; Hollema, H; tenHoor, KA; vanderZee, AGJ; Aalders, JG

    Purpose: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. Patients and Methods: Sere from 653 women treated for squamous cervical

  12. Expression of geminin, p16, and Ki67 in cervical intraepithelial neoplasm and normal tissues.

    Science.gov (United States)

    Xing, Yan; Wang, Chaojun; Wu, Jie

    2017-06-01

    Geminin is a protein involved in cell cycle progression. We aimed to evaluate the diagnostic value of geminin expression in cervical intraepithelial neoplasm (CIN).The expression of geminin, p16, and Ki67 was examined in 95 samples, including CIN1 (n = 45), CIN2/3 (n = 40), and normal cervical tissues (n = 10) by immunohistochemistry. The correlation between geminin or p16 expression and human papillomavirus (HPV) status was also evaluated.Geminin expression was negative in all normal tissues and expressed in 13.3% of CIN1 and 90.0% of CIN2/3. P16 expression was demonstrated in 24.4% of CIN1 and 87.5% of CIN2/3. The corresponding Ki67 expression was 35.6% and 95.0%. The specificity of geminin for differentiating between CIN1 and CIN2/3 was 86.7%, while for p16 and Ki67 the corresponding values were 75.6% and 64.4%. The sensitivity of geminin, p16, and Ki67 was 90.0%, 87.5%, and 95.0%, respectively. The positive predictive value (PPV) and accuracy of geminin were higher than p16 and Ki67. In addition, geminin expression showed a weak correlation with HPV status, but there was no association between p16 expression and HPV status.These results suggested that geminin had a high degree of sensitivity and specificity in determining CIN2/3. In addition to p16 and Ki67, geminin might be used as a new biomarker to distinguish between CIN1 and CIN2/3.

  13. Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2 Managed by Watchful Waiting

    Science.gov (United States)

    Ho, Gloria Y.F.; Einstein, Mark H.; Romney, Seymour L.; Kadish, Anna S.; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R.; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D.

    2013-01-01

    Objective This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed every 3 months without treatment. HPV genotyping, plasma levels of ascorbic acid, and red blood cell folate were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p< 0.001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared to HPV negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74 to 2.09) were at increased risk for persistent CIN; women with HPV 16/18 had the highest risk (RRs range = 1.91 to 2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50 – 2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusion Spontaneous regression of CIN 1 and CIN 2 occurs frequently within 12 months. HPV infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion. PMID:21811178

  14. Conization Using an Electrosurgical Knife for Cervical Intraepithelial Neoplasia and Microinvasive Carcinoma.

    Directory of Open Access Journals (Sweden)

    Libing Xiang

    Full Text Available The aim of the present study was to evaluate the incidences of margin involvement, disease relapse, and complications in patients who had undergone conization using an electrosurgical knife (EKC for cervical intraepithelial neoplasia (CIN or microinvasive carcinomas (micro-CAs.A retrospective case series analysis was performed with a total of 1359 patients who underwent EKC in Fudan University Shanghai Cancer Center between June 2004 and July 2010.The median age of the patients was 39 years old (range: 19-72. Conization revealed the presence of CIN in 1113 (81.9% patients, micro-CA in 72 (5.3% patients and invasive carcinomas in 44 (3.2% patients. The remaining 130 (9.6% patients were free of diseases in the cone specimens. Positive surgical margins, or endocervical curettages (ECCs were found in 90 (7.6% patients with CINs or micro-CAs. Three factors were associated with positive margins and ECCs and included age (>50 years; odds ratio (OR, 3.0, P<0.01, postmenopausal status (OR, 3.1, P<0.01 and microinvasive disease (OR, 2.7, P<0.01. One thousand and eighty-nine (92.0% patients were followed-up regularly for a median follow-up duration of 46 months (range: 24-106 months. Disease relapse was documented in 50 (4.6% patients. Eighty-two (6.0% cases experienced surgical complications that needed to be addressed, including early or late hemorrhages, infections, cervical stenosis, etc.Our patients demonstrated that EKC was an alternative technique for diagnosis and treatment of CIN or micro-CAs with relatively low rate of recurrence and acceptable rate of complications. A randomized clinical trial is warranted to compare EKC, CKC and LEEP in the management of CIN or micro-CA.

  15. Risk factors for treatment failure of CO2 laser vaporization in cervical intraepithelial neoplasia 2.

    Science.gov (United States)

    Yoon, Bo Sung; Seong, Seok Ju; Song, Taejong; Kim, Mi-La; Kim, Mi Kyoung

    2014-07-01

    The aim of our study was to evaluate the risk factors for treatment failure of CO2 laser vaporization in patients with cervical intraepithelial neoplasia 2 (CIN2). Medical records of patients who received either shallow or deep CO2 laser vaporization with biopsy-proven CIN2 during March 2007 to April 2011 were reviewed retrospectively. After laser vaporization, liquid-based cytology and human papilloma virus (HPV) DNA testing were checked in every follow-up visit. Treatment failure was defined when the follow-up biopsy was more than CIN2, needing secondary surgical treatment. During that period, 141 patients with CIN2 underwent CO2 laser vaporization. After laser ablation, 14 of 141 women needed the secondary treatment, a success rate of laser vaporization of 90.1 %. In multivariate analysis, the previous loop electrosurgical excision procedure (LEEP) history (adjusted OR = 13.649; P value = 0.025) and the ablation depth (adjusted OR = 11.279; P value = 0.006) were independent factors associated with treatment failure. Both ablation depth and previous LEEP history were the important factors increasing the risk for the treatment failure of CO2 laser vaporization in CIN2.

  16. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

    Science.gov (United States)

    Hoffman, Sarah R; Le, Tam; Lockhart, Alexandre; Sanusi, Ayodeji; Dal Santo, Leila; Davis, Meagan; McKinney, Dana A; Brown, Meagan; Poole, Charles; Willame, Corinne; Smith, Jennifer S

    2017-07-01

    A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates. © 2017 UICC.

  17. Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities.

    NARCIS (Netherlands)

    Hopman, A.H.N.; Smedts, F.; Dignef, W.; Ummelen, M.; Sonke, G.; Mravunac, M.; Vooijs, G.P.; Speel, E.J.; Ramaekers, F.C.S.

    2004-01-01

    Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by fluorescence in situ hybridization (FISH). In parallel,

  18. E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia

    Science.gov (United States)

    Brooks, L A; Sullivan, A; O'Nions, J; Bell, A; Dunne, B; Tidy, J A; Evans, D J; Osin, P; Vousden, K H; Gusterson, B; Farrell, P J; Storey, A; Gasco, M; Sakai, T; Crook, T

    2002-01-01

    In common with other E2F1 responsive genes such as p14ARF and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium. British Journal of Cancer (2002) 86, 263–268. DOI: 10.1038/sj/bjc/6600033 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11870517

  19. Retinoids for preventing the progression of cervical intra-epithelial neoplasia.

    Science.gov (United States)

    Helm, C William; Lorenz, Douglas J; Meyer, Nicholas J; Rising, William W R; Wulff, Judith L

    2013-06-06

    Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe cases of intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing the regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation that may have potential for the treatment of CIN. To ascertain whether retinoids can cause regression or prevent progression of CIN. We searched the Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), and MEDLINE and EMBASE (July 2010).For the 2013 update, the searches were re-run as follows: CENTRAL, Issue 3, 2013; MEDLINE, April, Week 2, 2013; and EMBASE, Week 16, 2013. Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women. Two review authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials. Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effects on CIN2 and CIN3 of the retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally. Two examined the effect of all-trans-retinoic acid administered topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally to human immunodeficiency virus (HIV)-positive participants with CIN1 and condyloma.Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, and the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported

  20. A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra-Anal 5% Imiquimod in HIV-1-Infected Men With High-Grade Squamous Intraepithelial Lesions.

    Science.gov (United States)

    Cranston, Ross D; Baker, Jonathan R; Siegel, Aaron; Brand, Rhonda M; Janocko, Laura; McGowan, Ian

    2018-01-22

    Imiquimod can be used to treat internal anal high-grade squamous intraepithelial lesions. In HIV-1-infected individuals there is a theoretical concern for increased HIV replication in anorectal tissue secondary to imiquimod-induced mucosal inflammation. The purpose of this study was to assess local virologic, immunologic, and pathologic effects of imiquimod treatment in HIV-infected individuals. This was a pilot study at a single academic center. The study was conducted at the University of Pittsburgh Anal Dysplasia Clinic. HIV-1-infected individuals with biopsy-confirmed internal anal high-grade squamous intraepithelial lesions were included. Imiquimod cream was prescribed for intra-anal use 3 times per week for 9 weeks. Anal human papillomavirus typing, anal and rectal tissue HIV-1 RNA and DNA quantification, cytokine gene expression, and anal histology were measured RESULTS:: Nine evaluable participants (1 participant was lost to follow-up) were all white men with a median age of 46 years (interquartile range = 12 y) and a median CD4 T-cell count of 480 cells per cubic millimeter (interquartile range = 835). All were taking antiretroviral therapy, and 7 of 9 had HIV-1 RNA anal or rectal tissue. Seven (35%) of 20 high-grade lesions resolved to low-grade squamous intraepithelial lesions. The study was limited by the small number of participants and variable time to final assessment. Intra-anal imiquimod showed no evidence of immune activation or increase in HIV-1 viral replication in anal and rectal tissue and confirmed efficacy for intra-anal high-grade squamous intraepithelial lesion treatment morbidity. See Video Abstract at, http://links.lww.com/DCR/A498.

  1. High Rates of Anal High-Grade Squamous Intraepithelial Lesions in HIV-Infected Women Who Do Not Meet Screening Guidelines.

    Science.gov (United States)

    Gaisa, Michael; Ita-Nagy, Fanny; Sigel, Keith; Arens, Yotam; Hennessy, Mary Ann; Rodriguez-Caprio, Gabriela; Mullen, Michael; Aberg, Judith A; Cespedes, Michelle

    2017-02-01

    Human immunodeficiency virus (HIV)-infected women have a higher burden of anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) compared with HIV-uninfected women. Guidelines for AC screening in this population are heterogeneous. Here we report outcomes and risk factors for anal HSIL following implementation of universal AC screening offered to all HIV-infected women. Data from women who underwent AC screening with anal cytology from April 2009 to July 2014 were analyzed. Routine clinical data included anal and cervical cytology, demographic/behavioral data, and high-resolution anoscopy (HRA) results. We evaluated the association of cytology with HRA results, and predictors of HSIL pathology, and compared rates of HSIL pathology among women meeting screening guidelines to those who did not. Seven hundred forty-five HIV-infected women were screened with anal cytology. Thirty-nine percent had abnormal anal cytology on initial screen and 15% on secondary screen; 208 women underwent HRA following abnormal anal cytology. HSIL was found in 26% and 18% of anal biopsies following initial and secondary screening, respectively. One woman had AC. Cigarette smoking more than doubled HSIL risk. Among women who underwent AC screening despite not meeting existing guideline criteria, 21% and 10%, respectively, were found to have HSIL on biopsy. Neither meeting criteria for screening nor history of receptive anal sex was significantly associated with HSIL. Anal HSIL is common in HIV-infected women. Substantial numbers of HSIL would have been missed by strictly adhering to existing AC screening guidelines. These results support routine screening of all HIV-infected women regardless of human papillomavirus history or sexual practices. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Differentiated squamous intraepithelial lesion (dSIL)-like changes in the epidermis overlying anogenital melanocytic nevi: A diagnostic pitfall.

    Science.gov (United States)

    Michalova, Kvetoslava; Kazakov, Dmitry V; Michal, Michael; Hadravsky, Ladislav; Kacerovska, Denisa; Rychly, Boris; Miesbauerova, Marketa; Michal, Michal

    2017-02-01

    Differentiated squamous intraepithelial lesion (dSIL) is morphologically and immunohistochemically analogous in the whole anogenital region. dSIL is a premalignant lesion frequently misinterpreted histopathologically as a benign dermatosis. The authors describe a peculiar change in the basal cell layer of the epidermis/epithelium overlying anogenital melanocytic nevi that may histopathologically imitate dSIL. The aim of this study is to familiarize the pathologists with this pitfall to avoid its possible overdiagnosis as dysplasia. Further, we tried to explore the biological characteristics of the dSIL-like changes and to focus on the differential diagnostic aspects. Seventy cases of anogenital nevi were retrieved from our registry. All cases were stained with hematoxylin and eosin (H&E) and reviewed. Cases in which the epidermis overlying nevi featured atypical appearing basal keratinocytes in otherwise fully differentiated epithelium, variable degrees of acanthosis and parakeratosis were selected for additional investigation. Thirty cases meeting the above described criteria were identified. The patients were 8 males and 22 females, with age at the time of diagnosis ranging from 4 to 68years. Follow-up data were available for 28 patients (range 0.5-19years, mean 5.1), and to date, no signs of epithelial malignancy have been recorded. Immunohistochemically (IHC), the epidermis overlying nevi showed insignificant positivity for p53 in all tested cases. Melanocytic markers (S-100 protein, SOX10, Melan A) and cytokeratin AE1/3 labeled melanocytes and keratinocytes, respectively, enabling their distinction, especially in nevi featuring a junctional component. Differentiated squamous intraepithelial lesion-like changes seem to occur relatively often in the epidermis overlying anogenital melanocytic nevi. Since morphologically they are virtually identical to the "true" dSIL, their distinction largely depends on p53 expression in basal keratinocytes with normal p53

  3. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease.

    Science.gov (United States)

    Kyrgiou, Maria; Athanasiou, Antonios; Kalliala, Ilkka E J; Paraskevaidi, Maria; Mitra, Anita; Martin-Hirsch, Pierre Pl; Arbyn, Marc; Bennett, Phillip; Paraskevaidis, Evangelos

    2017-11-02

    The mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent pregnancy, however, published studies and meta-analyses have reached contradictory conclusions. To assess the effect of local cervical treatment for CIN and early cervical cancer on obstetric outcomes (after 24 weeks of gestation) and to correlate these to the cone depth and comparison group used. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 5), MEDLINE (up to June week 4, 2017) and Embase (up to week 26, 2017). In an attempt to identify articles missed by the search or unpublished data, we contacted experts in the field and we handsearched the references of the retrieved articles and conference proceedings. We included all studies reporting on obstetric outcomes (more than 24 weeks of gestation) in women with or without a previous local cervical treatment for any grade of CIN or early cervical cancer (stage IA1). Treatment included both excisional and ablative methods. We excluded studies that had no untreated reference population, reported outcomes in women who had undergone treatment during pregnancy or had a high-risk treated or comparison group, or both DATA COLLECTION AND ANALYSIS: We classified studies according to the type of treatment and the obstetric endpoint. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model and inverse variance. Inter-study heterogeneity was assessed with I 2 statistics. We assessed maternal outcomes that included preterm birth (PTB) (spontaneous and threatened), preterm premature rupture of the membranes

  4. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears.

    Science.gov (United States)

    Szarewski, Anne; Ambroisine, Laurence; Cadman, Louise; Austin, Janet; Ho, Linda; Terry, George; Liddle, Stuart; Dina, Roberto; McCarthy, Julie; Buckley, Hilary; Bergeron, Christine; Soutter, Pat; Lyons, Deirdre; Cuzick, Jack

    2008-11-01

    The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%.

  5. Efficacy and safety of hexaminolevulinate photodynamic therapy in patients with low-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Hillemanns, Peter; Petry, Karl-Ulrich; Soergel, Philipp; Collinet, Pierre; Ardaens, Katty; Gallwas, Julia; Luyten, Alexander; Dannecker, Christian

    2014-08-01

    Non-surgical therapies are needed to reduce the rate of progression of low-grade cervical intraepithelial neoplasia (CIN 1) to high grade CIN (CIN 2/3). The aim of this study was to assess the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT) in the treatment of patients with CIN 1. This phase IIa prospective double-blind study randomized patients with CIN 1 into three groups: HAL vaginal suppository, placebo vaginal suppository or follow-up only. Patients in the first two groups received HAL or placebo suppositories 5 hours before illumination with 50 J/cm(2) red coherent light (633 nm) using a special light catheter. All patients had a follow up including colposcopy, cytology and human papilloma virus (HPV) testing 3 and 6 months and additional biopsy 6 months after PDT. The main outcome measure was efficacy, defined as complete histologic remission 6 months after PDT. Secondary outcomes were histologic remission 3 months and HPV eradication 6 months after first PDT. Seventy patients were randomized: 47 to HAL, 12 to placebo, 11 to follow up only. After 6 months CIN lesions had cleared in 57% of patients in the HAL-PDT group compared to 25% in the combined control group (per protocol population, P = 0.04). Twenty-six patients (37%) reported 44 adverse events (AEs), of which 40 were mild or moderate. Nineteen treatment-related AEs were reported by 15 patients (32%) in the HAL PDT group, one in the placebo PDT group (8%), and none in the follow-up group. The most common adverse events were local discomfort including mild pain/cramping (11) and leucorrhoea (2). HAL PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with CIN 1. © 2014 Wiley Periodicals, Inc.

  6. [Comparative study on the effects of LEEP and laser CO(2) vaporization in cervical intraepithelial neoplasia II].

    Science.gov (United States)

    Sun, Lu-Lu; Cao, Dong-Yan; Bian, Mei-Lu; Wei, Li-Hui; Yang, Jia-Xin; Yang, Li; Cheng, Ning-Hai; Wang, You-Fang; Cheng, Xue-Mei; Hu, Li-Jun; Lang, Jing-He; Shen, Keng

    2010-11-23

    to compare the effect and complications of loop electro-surgical excision procedure (LEEP) and laser CO(2) vaporization in the treatment of cervical intraepithelial neoplasia II. a total of 338 CINII women were recruited into this multi-center comparative study. The diagnosis was confirmed by histopathological examination for cervical epithelial cell abnormalities. And colposcopic examination was submitted to LEEP (n = 195) or laser CO(2) vaporization (n = 143) respectively. A post-treatment follow-up of 3, 6 and 12 months was carried out to compare the effect of two methods. among 195 women undergoing LEEP, the frequency of cure, persistent and recurrent CIN was 89.2% (n = 174), 4.1% (n = 8) and 3.6% (n = 7) respectively. And among 143 women receiving laser CO(2) vaporization, the frequency of cure, persistent and recurrent CIN was 86.7% (n = 124), 4.9% (n = 7) and 0.70% (n = 1) respectively. There was no statistical difference in cure rates, persistence or recurrence of CIN (P > 0.05). The recovery time, the operative frequency and intra-operative blood loss were significantly different in two groups. both LEEP and CO(2) vaporization are both effective and reliable for the treatment of cervical intraepithelial neoplasia II. However, pathological specimens may be harvested during LEEP. It is of vital importance to conduct preoperative colposcopic assessment and standard postoperative follow-ups.

  7. Spontaneous regression of low-grade cervical intraepithelial lesions is positively improved by topical bovine colostrum preparations (GINEDIE®). A multicentre, observational, italian pilot study.

    Science.gov (United States)

    Stefani, C; Liverani, C A; Bianco, V; Penna, C; Guarnieri, T; Comparetto, C; Monti, E; Valente, I; Pieralli, A L; Fiaschi, C; Origoni, M

    2014-01-01

    Human papillomavirus (HPV) is the causal agent of cervical cancer. The great majority of abnormal Pap test results - almost 90% - is referrable to either atypical squamous intraepithelial lesion or CIN1. For these lesions, worldwide agreement exists concerning the high rate - ranging from 40% to 70% - of spontaneous regression over a period of 1-5 years. Host's immune response is a key point influencing the natural history of these conditions. Bovine colostrum is a natural agent positively promoting several immune activities against bacterial and viral agents. The aim of this report was to evaluate the potential positive effect of bovine colostrum-containing vaginal tablets administered to CIN1 diagnosed patients in a prospective trial in regards to spontaneous regression rate. A series of 256 consecutive patients with histologically proven CIN1 recruited in a multicentre, observational, Italian study. Patients have been enrolled in a 24-weeks protocol of treatment and re-tested at the end of the study. Rates of regression have been recorded. Overall regression rate to a negative histology at the end of the 6 month follow up was 75.5%. Regression to normal histology was observed in a very high rate of cases in a very short period compared to the natural history of these lesions. CIN1 patients could benefit from bovine colostrum topical administration in terms of significantly shortening the regression time.

  8. High frequency of loss of heterozygosity in vulval intraepithelial neoplasia (VIN) is associated with invasive vulval squamous cell carcinoma (VSCC).

    Science.gov (United States)

    Rosenthal, A N; Ryan, A; Hopster, D; Surentheran, T; Jacobs, I J

    2001-12-15

    Vulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in vulval neoplasia has rarely been studied in this context. We performed LOH analysis by polymerase chain reaction (PCR) amplification of polymorphic microsatellite markers at 6 chromosomal loci (17p13-p53, 9p21-p16, 3p25, 4q21, 5p14 and 11p15). The presence of HPV was assessed using consensus PCR primers and DNA sequencing. To examine any association between LOH and the presence of invasive disease, we analyzed 43 cases of lone VIN III, 42 cases of lone VSCC and 21 cases of VIN with concurrent VSCC. HPV DNA was detected in 95% of lone VIN III samples and 71% of lone VSCC samples. Fractional regional allelic loss (FRL) in VIN associated with VSCC was higher than in lone VIN (mean FRL 0.43 vs. 0.21, p VIN, reflected by LOH, may increase the risk of invasion. In addition, molecular events differ in HPV-positive and -negative VSCC and 3p25 may be the site of a tumor suppressor gene involved in HPV-independent vulval carcinogenesis. Copyright 2001 Wiley-Liss, Inc.

  9. Impact of immunosuppression and region of birth on risk of cervical intraepithelial neoplasia among migrants living with HIV in Sweden.

    Science.gov (United States)

    Carlander, Christina; Wagner, Philippe; Svedhem, Veronica; Elfgren, Kristina; Westling, Katarina; Sönnerborg, Anders; Sparén, Pär

    2016-10-01

    Little is known about the incidence and risk of cervical intraepithelial neoplasia (CIN) grade 3, adenocarcinoma in situ and invasive cervical cancer (CIN3+) among migrants living with HIV in a European setting. We assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN2+ and CIN3+ in a cohort of women living with HIV (WLWH) (n = 893) identified from the Swedish national HIV register and HIV-negative women (n = 205,842) identified from the Swedish Population Register, matched on region of birth and age. Data was collected between 1993 and 2011 by linking our cohort with the Swedish National Cervical Screening Registry, collecting all cytological and histological results since 1993. The CuI of CIN3+ was 13.1% [95% confidence interval (CI) 8.9-17.2] for WLWH and 2.1% (95% CI 2.0-2.2) for HIV-negative after 18 years of follow-up. WLWH had more than eight times higher, age and region of birth matched, risk of CIN3+ than HIV-negative (HR 8.8: 95% CI 6.9-11.3). WLWH born in the East region, dominated by Thai women, had a two times higher risk of CIN3+ compared with WLWH born in Sweden (HR 2.47: 95% CI 1.2-5.0), which remained after adjusting for immunosuppression. Our results showed a substantially increased risk of CIN3+ among WLWH, which differed depending on birth region. Early HIV diagnosis and attendance to cervical cancer screening, with focus on migrants, is of crucial importance to minimize the incidence of cervical intraepithelial neoplasia. © 2016 UICC.

  10. Sialyl Lewis x expression in cervical scrapes of premalignant lesions

    Indian Academy of Sciences (India)

    In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous ...

  11. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18.

    Science.gov (United States)

    Fu Xi, Long; Schiffman, Mark; Ke, Yang; Hughes, James P; Galloway, Denise A; He, Zhonghu; Hulbert, Ayaka; Winer, Rachel L; Koutsky, Laura A; Kiviat, Nancy B

    2017-04-15

    Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log 10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log 10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. © 2017 UICC.

  12. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?

    Science.gov (United States)

    Mitra, Anita; MacIntyre, David A; Marchesi, Julian R; Lee, Yun S; Bennett, Phillip R; Kyrgiou, Maria

    2016-11-01

    The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.

  13. Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Kyrgiou, Maria; Mitra, Anita; Arbyn, Marc; Paraskevaidi, Maria; Athanasiou, Antonios; Martin-Hirsch, Pierre P L; Bennett, Phillip; Paraskevaidis, Evangelos

    2015-09-29

    Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P treatment

  14. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

    Science.gov (United States)

    Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

    2014-01-01

    Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: PHPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when ‘LSIL vs. HSIL’ assignment is

  15. Small lesion size measured by colposcopy may predict absence of cervical intraepithelial neoplasia in a large loop excision of the transformation zone specimen.

    Science.gov (United States)

    Munmany, M; Marimon, L; Cardona, M; Nonell, R; Juiz, M; Astudillo, R; Ordi, J; Torné, A; Del Pino, M

    2017-02-01

    To evaluate whether colposcopic measurement of the lesion size at diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in women treated for squamous intraepithelial lesions/cervical intraepithelial neoplasia (SIL/CIN). Prospective observational study. Tertiary university hospital. A cohort of 116 women who underwent LLETZ because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or because of a high-grade SIL/CIN diagnosed in the referral visit and squamocolumnar junction completely visible (types 1 or 2, according to the International Federation of Cervical Pathology and Colposcopy, IFCPC). After LLETZ the women were classified by histology into the study group (absence of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group (SIL/CIN in the LLETZ specimen, 88/116, 75.9%). The size of the lesion determined in the diagnostic colposcopy and the HPV genotype were evaluated in all women. The lesion size was significantly smaller in the study group (25.7 ± 37.8 versus 84.5 ± 81.7 mm 2 ; P lesion size of ≤12 mm 2 and HPV types other than 16 or 18 were associated with an absence of SIL/CIN in the LLETZ specimen (P lesion size of ≤12 mm 2 predicted the absence of SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P lesion size of ≤12 mm 2 had a specificity of 90.9% (95% CI 83.0-95.3%) and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the absence of SIL/CIN in the surgical specimen. Small lesion size in diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen. Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary treatment. Small lesion size in colposcopic evaluation might predict the absence of SIL/CIN in an LLETZ specimen. © 2016 Royal College of Obstetricians and Gynaecologists.

  16. Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

    Science.gov (United States)

    Tokmak, Aytekin; Guzel, Ali Irfan; Ozgu, Emre; Oz, Murat; Akbay, Serap; Erkaya, Salim; Gungor, Tayfun

    2014-01-01

    To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

  17. 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

    2017-11-15

    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 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.

  18. Molecular detection of human papillomavirus in Brazilian women with cervical intraepithelial neoplasia in a northeast Brazilian city.

    Science.gov (United States)

    Nunes, J D C; Vidal, F C B; Ferraro, C T L; Chein, M B C; Brito, L M O; Monteiro, S C M

    2014-10-31

    We examined the prevalence of human papillomavirus (HPV) infection in Brazilian women with cervical intraepithelial neoplasia. Our goal was to identify the types of HPV and their association with risk factors. This prospective cross-sectional study included 97 samples collected from women aged 14-79 years at the public health units of gynecological care in São Luís, MA, Brazil. HPV detection was performed by nested polymerase chain reaction and sequence analysis. The study patients completed a structured questionnaire to provide information regarding their socio-demographic, clinical, and behavioral status. HPV prevalence was found to be 80.4%, with 17 virus types detected, including HPV 16, 18, 58, 6, and 11. Significant associations between HPV infection and age and frequency of doctor visits were identified. The study findings indicate the significance of age and low frequency of visits to the gynecologist as risk factors for genital HPV infection, suggesting that HPV infection-derived cervical cancer could be prevented through orientation programs for women, which include sex education and information regarding screening tests. We also found an increased prevalence of high-risk HPV serotypes in cervical lesions, which reveals an association between cervical lesions and high-risk HPV.

  19. Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Huusom, Lene D; Andersen, Klaus K

    2015-01-01

    Little research has been conducted on the long-term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long-term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we...

  20. The negative predictive value of p16INK4a to assess the outcome of cervical intraepithelial neoplasia 1 in the uterine cervix

    DEFF Research Database (Denmark)

    Hariri, Jalil; Øster, Anne

    2007-01-01

    The immunohistochemical expression of p16 in formalin-fixed and paraffin-embedded histological sections was evaluated in a retrospective study comprising a low-grade group of 100 cases of cervical intraepithelial neoplasia (CIN) 1, a high-grade group of 50 cases of CIN 2 to 3, and a benign group ...

  1. Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization

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    Fu Y

    2015-05-01

    Full Text Available Yunfeng Fu,1,2,* Chen Chen,3,* Suwen Feng,2 Xiaodong Cheng,2 Xinyu Wang,1,2 Xing Xie,1,2 Weiguo Lü2 1Department of Gynecology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, 2Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 3Second Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study was to determine the clinicopathologic predictors of residual disease in patients with high-grade cervical intraepithelial neoplasia (CIN and margin involvement after initial conization.Methods: Data from 145 patients who underwent subsequent surgery for high-grade CIN with positive margins were retrospectively analyzed.Results: After subsequent surgery, residual disease was diagnosed in 47 (34.2% patients, of whom five had invasive cervical carcinoma, 31 had CIN 3, nine had CIN 2, and two had CIN 1. Multivariate analysis revealed that only age ≥35 years (P=0.033, major abnormal cytology (P=0.002, and pre-cone high-risk human papillomavirus load ≥300 relative light units (P=0.011 were significant factors associated with residual disease.Conclusion: Age ≥35 years, major abnormal cytology, and pre-cone high-risk human papillomavirus load ≥300 relative light units were the only significant factors predicting post-cone residual disease. Appropriate application of these predictive factors may avoid delayed treatment and overtreatment. Keywords: cervical intraepithelial neoplasia, residual disease, conization, positive margin, predictor

  2. Efficacy in treatment of subclinical cervical HPV infection without intraepithelial neoplasia: systematic review

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    Fábio Russomano

    2000-07-01

    Full Text Available CONTEXT: The treatment of the subclinical Human papillomavirus (HPV infection of the uterine cervix is controversial. OBJECTIVE: To assess the efficacy of any therapy for subclinical HPV infection of the cervix without intraepithelial neoplasia, via a search in the medical literature. METHOD: We performed a systematic review with a comprehensive reference search in Medline, LILACS, Excerpta Medica, AIDSLINE, Popline, Cochrane Library and other authors' reference lists to identify experimental studies of therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. In order to identify unpublished studies, we also contacted experts in the area, clinical trial registries, pharmaceutical industries, government and research institutions. We also searched on the Internet and in the book-of-abstracts of some medical conferences. The studies identified were masked and selected by inclusion criteria to help ascertain their internal validity. The data about regression or progression of HPV infection were extracted from the studies included. RESULTS: We identified 67 studies related to the treatment of subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. Only five clinical trials matched the inclusion criteria and none demonstrated significant differences between the experimental group and the control group concerning regression of HPV infection (with or without CIN I or progression to higher grades of CIN. CONCLUSION: The evidence we found in the medical literature regarding the efficacy of any therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix was unsatisfactory.

  3. 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.

  4. Oncogenic human papillomavirus genotypes and the diagnosis of cervical intraepithelial neoplasia

    NARCIS (Netherlands)

    Marel, J. van der

    2015-01-01

    Cervical cancer is the fourth most common cancer in women, with more than half a million new cases worldwide each year. In the majority of cervical cancers a persistent infection with high-risk (hr) Human papillomavirus (HPV) types has been proven to be the causative agent. Prevention of cervical

  5. Implications of morphologic patterns of intraepithelial microvasculature observed by narrow-band imaging system in cases of oral squamous cell carcinoma.

    Science.gov (United States)

    Yang, Shih-Wei; Lee, Yun-Shien; Chang, Liang-Che; Hsieh, Tsan-Yu; Chen, Tai-An

    2013-01-01

    To investigate the intraepithelial microvascular morphology of oral squamous cell carcinoma (OSCC) by using narrow-band imaging (NBI) and analyze whether the intraepithelial papillary capillary loop (IPCL) patterns correlate with infiltration depth and disease severity in OSCC. The clinicopathologic data, morphology of vascular architecture as observed by NBI, and histopathology of patients with OSCC were retrospectively reviewed and analyzed. A total of 80 patients, including 73 males and 7 females with an average age of 54.18±12.23 years, were enrolled. Three patterns of intraepithelial microvasculature were revealed by NBI and differences in these three patterns were significant with regard to pathologic T-classification (p<0.0001), N-classification (p=0.00022), TNM stage (p<0.0001), lymphovascular invasion (p<0.0001), perineural invasion (p=0.000299), depth of tumor infiltration (p<0.0001), and tumor differentiation (p<0.0001). A cut-off point of tumor infiltration of 10.012 mm was best predicted for the destructive pattern of IPCL (sensitivity=100%, specificity=90.0%). Three different patterns of IPCL, showing step-wise increased severity according to pathologic parameters, were observed by NBI in cases of OSCC. The pattern indicating IPCL destruction with angiogenesis was associated with more advanced disease stage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Potential impact of a nonavalent HPV vaccine on HPV related low-and high-grade cervical intraepithelial lesions: A referral hospital-based study in Sicily.

    Science.gov (United States)

    Capra, Giuseppina; Giovannelli, Lucia; Matranga, Domenica; Bellavia, Carmelina; Guarneri, Maria Francesca; Fasciana, Teresa; Scaduto, Giovanna; Firenze, Alberto; Vassiliadis, Alessandra; Perino, Antonio

    2017-08-03

    While bivalent and quadrivalent HPV vaccines have been used for about 10 years, a nonavalent vaccine against HPV types 6/11/16/18/31/33/45/52 and 58 has been recently approved by FDA and EMA and is now commercially available. The objective of our study was to evaluate the potential impact of the nonavalent vaccine on HPV infection and related low- and high-grade squamous intraepithelial lesions (LSIL, HSIL), compared to the impact of the quadrivalent vaccine, in a female population living in Sicily (Italy). Low estimates of HPV vaccine impact were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes, alone or in association, but excluding presence of other HPV types; high estimates were calculated as prevalence of HPV 6/11/16/18/31/33/45/52 and 58 genotypes alone or in association, in the presence of other HPV types. The nonavalent HPV vaccine showed increased impact, compared to the quadrivalent vaccine. Estimates of potential impact varied from 30.9% (low estimate) to 53.3% (high estimate) for LSIL, and from 56.9% to 81,0% for HSIL. The proportion of additional cases potentially prevented by the nonavalent vaccine was 14.4%-23.8% for LSIL, and 19.0%-32.8% for HSIL. The benefit of the nonavalent vaccine compared to the quadrivalent vaccine was more than 80% for both low and high impact estimates for LSIL and more than 50% for both low and high impact estimates for HSIL. The present study confirms that the switch from a first generation HPV vaccines to a nonavalent vaccine would increase the prevention of cervical HSIL in up to 90% of cases.

  8. Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico.

    Science.gov (United States)

    López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

    2009-02-16

    In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype.

  9. Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing.

    Science.gov (United States)

    Gomes de Oliveira, Geilson; Eleutério, Renata Mirian Nunes; Silveira Gonçalves, Ana Katherine; Giraldo, Paulo César; Eleutério, José

    2017-11-08

    The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology. © 2017 S. Karger AG, Basel.

  10. Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, P A; Mandel, U; Therkildsen, M H

    1997-01-01

    with the cell membrane, but the identity of the carrier molecule(s) remains largely unknown. We report here the identification of a membrane-bound M(r) 200,000-250,000 glycoprotein (gp230) that is expressed in stratified squamous epithelia of the oral cavity. Western blot analysis identified gp230 as a major...... epithelial dysplasia and squamous cell carcinomas of oral and cervical mucosa....... layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately...

  11. Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hu YF

    2015-08-01

    Full Text Available Yun-Feng Hu,1 Xia Lei,2 Hong-Yi Zhang,3 Jun-wei Ma,1 Wei-wei Yang,1 Min-lin Chen,1 Jie Cui,1,4 Hong Zhao1 1Department of Oncology, 2Department of Gynecology, 3Department of Urology, Yan’an University Affiliated Hospital, Yan’an, Shaanxi Province, People’s Republic of China; 4Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Purpose: We aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.Methods: Beclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous cell carcinoma (SCC, 40 samples of high-grade cervical intraepithelial neoplasia (CIN, and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ2 and Fisher’s exact tests. Differences in overall survival (OS were determined using the Kaplan–Meier method and log-rank tests.Results: Cervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000. Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000. No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of

  12. 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

  13. Development of a goat model for evaluation of withaferin A: Cervical implants for the treatment of cervical intraepithelial neoplasia.

    Science.gov (United States)

    Sherwood, Leslie C; Aqil, Farrukh; Vadhanam, Manicka V; Jeyabalan, Jeyaprakash; Munagala, Radha; Hoetker, David; Srivastava, Sanjay; Singh, Inder P; Cambron, Scott; O'Toole, Martin; Spencer, Wendy; Parker, Lynn P; Gupta, Ramesh C

    2017-12-01

    Cervical cancer is caused by human papillomavirus (HPV). The disease develops over many years through a series of precancerous lesions. Cervical cancer can be prevented by HPV-vaccination, screening and treatment of precancer before development of cervical cancer. The treatment of high-grade cervical dysplasia (CIN 2+) has traditionally been by cervical conization. Surgical procedures are associated with increased risk of undesirable side effects including bleeding, infection, scarring (stenosis), infertility and complications in later pregnancies. An inexpensive, non-invasive method of delivering therapeutics locally will be favorable to treat precancerous cervical lesions without damaging healthy tissue. The feasibility and safety of a sustained, continuous drug-releasing cervical polymeric implant for use in clinical trials was studied using a large animal model. The goat (Capra hircus), non-pregnant adult female Boer goats, was chosen due to similarities in cervical dimensions to the human. Estrus was induced with progesterone CIDR® vaginal implants for 14days followed by the administration of chorionic gonadotropins 48h prior to removal of the progesterone implants to relax the cervix to allow for the placement of the cervical implant. Cervical implants, containing 2% and 4% withaferin A (WFA), with 8 coats of blank polymer, provided sustained release for a long duration and were used for the animal study. The 'mushroom'-shaped cervical polymeric implant, originally designed for women required redesigning to be accommodated within the goat cervix. The cervical implants were well tolerated by the animals with no obvious evidence of discomfort, systemic or local inflammation or toxicity. In addition, we developed a new method to analyze tissue WFA levels by solvent extractions and LS/MS-MS. WFA was found to be localized to the target and adjacent tissues with 12-16ng WFA/g tissue, with essentially no detectable WFA in distant tissues. This study suggests that

  14. Virological and cytological clearance in laser vaporization and conization for cervical intra-epithelial neoplasia grade 3.

    Science.gov (United States)

    Mariya, Tasuku; Nishikawa, Akira; Sogawa, Kanae; Suzuki, Riri; Saito, Masae; Kawamata, Akari; Shimizu, Ayumi; Nihei, Takehito; Sonoda, Tomoko; Saito, Tsuyoshi

    2016-12-01

    Cervical intra-epithelial neoplasia (CIN) is the precancerous stage of cervical cancer. Standard treatment for high-grade CIN is conization of the cervix. The risk of preterm birth following conization has been discussed recently. In contrast, laser vaporization is believed not to affect perinatal outcome, but the long-term effectiveness of each surgical procedure is still unclear. The aim of this prospective unmatched-cohort study was therefore to compare virological and cytological clearance and recurrence risk between conization and vaporization for CIN3. Subject consisted of CIN3 patients treated at the present hospital between 2007 to 2011 and followed up until December 2014. One hundred and one patients were treated with laser conization, and 137 with vaporization. The surgical procedure was selected on the basis of colposcopy, pathological grade and patient's hope for pregnancy. There were no significant differences in cure rate, human papilloma virus (HPV) clearance rate or recurrence rates between the conization and vaporization groups. Risk ratio of recurrence for each surgical procedure adjusted for age and HPV persistence status were analyzed on Cox proportional hazards modeling. Recurrence risk ratio for patients treated by vaporization was 6.21 (95%CI: 0.65-59.19; P = 0.111) compared with conization and there were no significant differences. No adverse pregnancy outcome was observed in the vaporization group compared with conization. Laser vaporization is useful for young patients with CIN3 who hope for pregnancy in the future. © 2016 Japan Society of Obstetrics and Gynecology.

  15. An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

    Directory of Open Access Journals (Sweden)

    Panagiotis Bountris

    2014-01-01

    Full Text Available Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV, including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS, composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%, high specificity (97.1%, high positive predictive value (89.4%, and high negative predictive value (97.1%, for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+. In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

  16. An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

    Science.gov (United States)

    Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

    2014-01-01

    Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

  17. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja

    2015-12-01

    Full Text Available BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  18. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

    Directory of Open Access Journals (Sweden)

    Edhyana Sahiratmadja

    2014-04-01

    Full Text Available Background Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. Methods During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. Results Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. Conclusion The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  19. Cervical pap smear- A prospective study in a tertiary hospital

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    S Pudasaini

    2015-09-01

    Full Text Available Background: Cervical cancer is a leading cause of mortality and morbidity among women worldwide and most common gynaecological cancer in developing countries. Papanicolaou smear is a simple and cost effective screening test for cervical cancer. The aim of this study is to evaluate and interpret the cervical pap smear cytology in a tertiary hospital. The interpretation and reporting of the pap smear is based on 2001Bethesda system.Materials and methods: This is a prospective study conducted in a tertiary hospital, Nepal Medical College over a period of two and a half years (January 2013 to June 2015. All cervical pap smears received in the department of Pathology in the study period were included.Results: A total of 4160 cervical pap smears were reported in the study period. Majority of the cases were Negative for Intraepithelial lesion or malignancy (87.9%. Bacterial vaginosis, atrophy and reactive cellular changes associated with inflammation were seen in 5.3%, 2.4% and 1.5% cases respectively.   Epithelial cell abnormalities (0.5% include Atypical squamous cells of undetermined significance, Low grade squamous intraepithelial lesion and High grade intraepithelial lesion. 88% of Low grade squamous intraepithelial lesion was seen in reproductive age group (20-45 years.Conclusion: Cervical cancer is the most common gynaecological cancer in the developing countries. Pap smear is the simple and cost effective screening tool to detect pre invasive cervical epithelial lesions.

  20. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

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

    2015-01-01

    In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...

  1. Histomorfometria, apoptose e proliferação celular em neoplasias intraepiteliais do colo uterino Histomorphometry, apoptosis and cell proliferation in cervical intraepithelial neoplasia

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    Rodrigo Tadeu de Puy e Souza

    2011-12-01

    Full Text Available INTRODUÇÃO: As displasias do colo uterino são precursoras do carcinoma de células escamosas. Mutações induzidas por carcinógenos correlacionam-se com alterações proliferativas. O acúmulo dessas mutações e o descontrole da homeostase genômica permitem mudanças na expressão de determinados genes e geram desequilíbrios na proliferação celular e na apoptose. Marcadores imuno-histoquímicos de proliferação celular, de apoptose e de sobrevivência celular em lesões intraepiteliais cervicais ainda necessitam de estudo morfométricos para definir seus papéis na evolução das displasias ao carcinoma invasivo. OBJETIVOS: Para melhor entender os processos de proliferação celular, apoptose e renovação epitelial nessas lesões, foram realizadas histomorfometria para mitose e apoptose e reações imuno-histoquímicas das proteínas Bax, Bcl-2 e Ki-67 (reatividade, localização e intensidade em biópsias cervicais. MÉTODOS: As amostras foram divididas em quatro grupos: 1. cervicite (n = 20; 2. displasia leve (n = 20; 3. displasia moderada (n = 20; 4. displasia acentuada (n = 20. RESULTADOS: Foram verificadas intensa proliferação celular e apoptose nas lesões de alto grau e ampla, intensa e difusa imunomarcação para Ki-67 e Bax. Esses achados foram encontrados de maneira discreta ou nula nos grupos cervicite e displasia leve. A marcação para Bcl-2 foi mais intensa nas lesões de alto grau, tendo sido discreta nas demais. A ampla marcação imuno-histoquímica de Ki-67 e Bax é sugestiva de elevado grau de renovação celular, o qual também é sustentado pela histomorfometria. A expressão do Bcl-2 aumenta com a gravidade da displasia. CONCLUSÃO: Esses achados indicam que o processo pré-neoplásico é dinâmico, com apoptose e mitose ocorrendo concomitantemente.INTRODUCTION: Cervical dysplasias are precursor to squamous cell carcinoma of the uterine cervix. Carcinogen induced mutations correlate with proliferative

  2. Prevalence of human papillomavirus in the cervical epithelium of Mexican women: meta-analysis

    OpenAIRE

    Peralta-Rodríguez Raúl; Romero-Morelos Pablo; Villegas-Ruíz Vanessa; Mendoza-Rodríguez Mónica; Taniguchi-Ponciano Keiko; González-Yebra Beatriz; Marrero-Rodríguez Daniel; Salcedo Mauricio

    2012-01-01

    Abstract Background Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous ...

  3. High-grade cervical intraepithelial neoplasia during pregnancy: experience in a service in southern Brazil

    OpenAIRE

    Preti, Vinícius Basso; Hatschbach, Sérgio Bruno Bonatto; Linhares, José Clemente; Guerreiro, João Antônio; Minari, Claudiane Lígia; Maestri, Carlos Afonso; Fonseca, Fernanda Villar

    2009-01-01

    OBJETIVO: avaliar o tratamento instituído a portadoras de neoplasia intraepitelial cervical de alto grau e o seguimento destas pacientes durante a gestação. MÉTODOS: estudo retrospectivo baseado na revisão dos prontuários de 30 pacientes atendidas no período de 1990 a 2002 no Hospital Erasto Gaertner, com diagnóstico de neoplasia intraepitelial cervical de alto grau durante a gestação. O diagnóstico foi realizado por colposcopia e biópsia, e a colposcopia foi realizada novamente durante o per...

  4. Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies.

    Science.gov (United States)

    Zhao, Fang-Hui; Lewkowitz, Adam K; Hu, Shang-Ying; Chen, Feng; Li, Long-Yu; Zhang, Qing-Ming; Wu, Rui-Fang; Li, Chang-Qing; Wei, Li-Hui; Xu, Ai-Di; Zhang, Wen-Hua; Pan, Qin-Jing; Zhang, Xun; Belinson, Jerome L; Sellors, John W; Smith, Jennifer S; Qiao, You-Lin; Franceschi, Silvia

    2012-12-15

    High-risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR-HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population-based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid-based cytology. Women positive for any test received colposcopy-directed or four-quadrant biopsies. A total of 29,579 women had HR-HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR-HPV prevalence was 17.7%. HR-HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25-29 (11.3%) in rural and at age 35-39 (11.3%) in urban women. In rural and urban women, age-standardized CIN2 prevalence was 1.5% [95% confidence interval (CI): 1.4-1.6%] and 0.7% (95% CI: 0.7-0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2-1.3%) and 0.6% (95% CI: 0.5-0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR-HPV-positive women steadily increased with age, peaking in 45- to 49-year-old women. High prevalence of HR-HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45-49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported. Copyright © 2012 UICC.

  5. LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia.

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    Barchitta, Martina; Quattrocchi, Annalisa; Maugeri, Andrea; Canto, Carolina; La Rosa, Nadia; Cantarella, Maria Antonietta; Spampinato, Giuseppa; Scalisi, Aurora; Agodi, Antonella

    2017-08-30

    Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women. Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion. Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01-1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%). LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations

  6. The risk of preterm birth of treated versus untreated cervical intraepithelial neoplasia (CIN): a systematic review and meta-analysis.

    Science.gov (United States)

    Danhof, Nora A; Kamphuis, Esme I; Limpens, Jacqueline; van Lonkhuijzen, Luc R C W; Pajkrt, Eva; Mol, Ben W J

    2015-05-01

    Cervical surgery is associated with preterm birth (PTB) and neonatal morbidity. However, it is unknown whether this increased risk is due to the surgery itself or to the cervical intraepithelial neoplasia (CIN) underlying the surgery. Our objective was to assess the risk for PTB in women with treated and untreated CIN. We performed an electronic literature search in MEDLINE, Embase and CENTRAL for studies that reported on pregnancy outcome after treated and untreated CIN. The methodological quality was scored using the STROBE combined checklist for observational studies. We extracted data on PTBpremature rupture of membranes ((P)PROM), perinatal mortality and section caesarean each before and after treatment for CIN. We used the Mantel-Haenszel method to estimate summarizing odds ratios. Our search identified 620 studies, of which 20 were reporting on pregnancy outcome for a total of 12,159,293 women. There were 20,832 women who gave birth after treatment for CIN before pregnancy, 52 women who gave birth after treatment for CIN during pregnancy, 64,237 women with CIN who gave birth before treatment, and 8,902,865 women who gave birth without CIN. Compared to women with untreated CIN, women treated for CIN before or during pregnancy, had a significantly higher risk of PTB<37 weeks (OR 1.7, 95% CI 1.0-2.7). When comparing women treated for CIN before pregnancy (n=20,832) to women with untreated CIN (n=64,162), we found an OR of 1.4 with a 95% confidence interval of 0.85-2.3. Women treated during pregnancy had a clearly increased risk for PTB (OR 6.5, 95% CI 1.1-37), and (P)PROM (OR 1.8, 95% CI 1.4-2.2). In women with cervical surgery, the risks for spontaneous PTB<37 weeks (OR 0.87, 95% CI 0.54-1.4), caesarean section (OR 1.0, 95% CI 0.71-1.5) and perinatal mortality (OR 1.0, 95% CI 0.38-2.8) were not increased. The increased risk of PTB in women who underwent cervical surgery for CIN is especially increased when performed during pregnancy. When performed before

  7. 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

  8. Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women

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    Brooke E. Howitt

    2017-06-01

    Full Text Available Purpose: Cervical squamous cell carcinoma (SCC continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. Materials and Methods: In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. Results: Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%, followed by HPV 18 (34%, HPV 35 (24%, and HPV 31 (12%. A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58 would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy. The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients. Conclusion: Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.

  9. Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women.

    Science.gov (United States)

    Howitt, Brooke E; Herfs, Michael; Tomoka, Tamiwe; Kamiza, Steve; Gheit, Tarik; Tommasino, Massimo; Delvenne, Philippe; Crum, Christopher P; Milner, Danny

    2017-06-01

    Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58) would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy). The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients. Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.

  10. Performance of the cobas HPV Test for the Triage of Atypical Squamous Cells of Undetermined Significance Cytology in Cervical Specimens Collected in SurePath.

    Science.gov (United States)

    Tewari, Devansu; Novak-Weekley, Susan; Hong, Christina; Aslam, Shagufta; Behrens, Catherine M

    2017-11-02

    Determine performance of the cobas human papillomavirus (HPV) test for triage of atypical squamous cells of undetermined significance (ASC-US) in SurePath. Women presenting for routine screening had cervical specimens collected in SurePath and specimen transport medium (STM); those with ASC-US cytology underwent colposcopy. Performance of cobas HPV in SurePath specimens that had undergone a preanalytic procedure to reverse possible cross-linking of HPV DNA was compared with Hybrid Capture 2 (hc2) specimens in STM. Among 856 women, HPV prevalence was 45.8%; HPV 16 and HPV 18 prevalences were lower than expected in the 21- to 29-year-old group in this highly vaccinated population. cobas HPV performance in SurePath was comparable to hc2 in STM. Sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 3 or worse were 87.5% (95% confidence interval [CI], 71.9%-95.2%) and 55.5% (95% CI, 52.1%-58.9%) for cobas and 85.3% (95% CI, 69.9%-93.6%) and 54.7% (95% CI, 51.4%-57.9%) for hc2. Sensitivity was negatively affected by random biopsies performed at colposcopy; comparable sensitivities were achieved in the nonvaccinated and vaccinated populations with disease determined by directed biopsy only. Performance of cobas HPV for ASC-US triage in pretreated SurePath specimens meets criteria for validation. Preliminary data indicate reliable performance of HPV testing in a highly vaccinated population.

  11. Incidence of ano-genital and head and neck malignancies in women with a previous diagnosis of cervical intraepithelial neoplasia.

    Science.gov (United States)

    Gaudet, Marc; Hamm, Jeremy; Aquino-Parsons, Christina

    2014-09-01

    The objective of this study was to determine if women with a history of Cervical Intraepithelial Neoplasia grades 2 and 3 (CIN2 and CIN3) are at increased long-term risk for developing non-cervix HPV-related malignancies. Women diagnosed with CIN2 or CIN3 between 1980 and 2005 were identified from the British Columbia (BC) Cancer Agency Cervical Cancer Screening Program's database. These patients' records were then cross-referenced with the BC Cancer Registry for diagnosis of vulvar, vaginal, anal or head and neck (HN) cancers during the period subsequent to their diagnosis of CIN. Standardized incidence ratios (SIR) were generated according to expected rates of each cancer. 54,320 women with a diagnosis of CIN2 or CIN3 were identified between 1985 and 2005. The crude incidence rate for non-cervix HPV-related cancers was 35.4 per 100,000 person-years (8.6 for vagina, 17.6 for vulva, 3.7 for anal canal and 5.5 for HN). The SIR was 1.9 (95% CI 1.3-2.7) for all non-cervix cancers, 6.7 (95% CI: 3.0-12.8) for vagina, 2.9 (95% CI: 1.7-4.6) for vulva, 1.8 (95% CI: 0.4-4.7) for anal canal, and 0.6 (95% CI: 0.2-1.4) for HN. There were statistically significant increases in anal cancers for years 5-9 and in HN cancers for years 0.5-5. BC women with a history of CIN2 or CIN3 are at relatively high risk of developing non-cervical HPV-related malignancies. The findings of this study suggest that interventions such as vaccination against high-risk HPV or long-term screening for these other cancers should be evaluated. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  12. Detection of abnormal cervical cytology in Papanicolaou smears

    Science.gov (United States)

    Bal, Manjit Singh; Goyal, Rishu; Suri, Anil Kumar; Mohi, Manjit Kaur

    2012-01-01

    Background: Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions. Cervical intra-epithelial neoplasia (CIN) and cervical cancer remain important health problems for women worldwide. Aim: To study the role of Pap smear in detecting premalignant and malignant lesions of cervix; and to determine the prevalence of various lesions. Materials and Methods: This study is based on 300 patients who attended the out-patient Department of Obstetrics and Gynaecology. Pap smears were prepared from patients presenting with complaints like vaginal discharge, post-coital bleeding, inter-menstrual bleeding, dyspareunia, and pain lower abdomen. After fixation and staining, each smear was carefully examined. Results: Epithelial cell abnormalities were found in 5% smears, atypical squamous cells of undetermined significance (ASCUS) in 0.3%, squamous intraepithelial lesion (SIL) in 3.4% which includes low grade squamous intraepithelial lesion (LSIL) (2.7%) and high grade squamous intraepithelial lesion (HSIL) 0.7%. Invasive carcinoma was seen in 1.3% cases. Mean age of the patients with diagnosis of LSIL was 32.3 years and for HSIL, it was 40.5 years. The mean age of the patients with invasive carcinoma was 57 years. Conclusion: Premalignant and malignant lesions of cervix are not uncommon in our set up and can be diagnosed early by Pap smears. PMID:22438616

  13. HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.

    Science.gov (United States)

    Maniar, Kruti P; Nayar, Ritu

    2014-09-01

    Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.

  14. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

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    Imajoh Masayuki

    2012-08-01

    Full Text Available Abstract Background Merkel cell polyomavirus (MCPyV was identified originally in Merkel cell carcinoma (MCC, a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i the major histological type of cervical cancer is the SCC; (ii the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV. In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19% and 4/16 cervical ACs (25% were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset

  15. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients.

    Science.gov (United States)

    Imajoh, Masayuki; Hashida, Yumiko; Nemoto, Yuiko; Oguri, Hiroyoshi; Maeda, Nagamasa; Furihata, Mutsuo; Fukaya, Takao; Daibata, Masanori

    2012-08-09

    Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. This study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from

  16. Características de um grupo de adolescentes com suspeita de neoplasia intra-epitelial cervical Characteristics of a group of adolescents with suspected cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Maria Isabel do Nascimento

    2005-10-01

    suspected cervical neoplasia and to compare it with young adult women. METHODS: a cross-sectional, retrospective study that analyzed 366 medical records of females referred to clarify diagnosis of the suspected cervical neoplasia. The patients had been classified into two groups defined by age. The Adolescent group was composed of 129 females between 13 and 19 years and the Adult group was composed of 237 females between 20 and 24 years. Data were analyzed statistically by the prevalence ratio (PR, respective confidence intervals (CI at 95% for each variable, chi2 test, or Fisher exact test used to compare proportion. RESULTS: the first sexual intercourse coitarche occurred on average at 15.0 years in the Adolescent group and 16.6 years in the Adult group. The possibility of diagnosis of cytological alterations in the first Papanicolaou smears (PR=2.61; CI 95%: 2.0-3,4, the condition of non-clarified cervical intraepithelial neoplasia (CIN (PR=1.78; CI 95%: 1.26-2,52, and the colposcopic impressions of low grade (PR=1.42; CI 95%: 1.08-1.86 were statistically significant in the Adolescent group. The histopathologic analysis did not show differences at any grade of CIN. However, two cases of microinvasive carcinoma, one in each group, and three cases of clinical invasive carcinoma in the Adult group were identified. CONCLUSION: our study suggests that cervical cancer is rare among adolescents, but we verified that alterations associated with it occurred even in younger women. The evaluation of cervical intraepithelial neoplasia with the careful application of the same tools used for adult women was appropriate also in adolescence.

  17. 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/E7mes......messenger RNA (mRNA), and preliminary data suggest that they might have a higher specificity. However, mRNA is less stable than DNA, thus posing a challenge to the preservation abilities of the cell-collecting medium.......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...

  18. [Patterns of cervical metastasis from squamous cell carcinoma of the head and neck].

    Science.gov (United States)

    Aksoy, Fadlullah; Veyseller, Bayram; Binay, Omer; Apuhan, Tayfun; Yıldırım, Yavuz Selim; Ozturan, Orhan

    2010-01-01

    In this study, the existence, distribution and characteristics of cervical lymph nodes metastases in patients with laryngeal, hypopharyngeal and intraoral squamous cell cancer were investigated. A retrospective review of the charts of 81 laryngeal, hypopharyngeal and intraoral cancer patients (10 females, 71 males; mean age 55.9 years; range 30 and 81 years) surgically treated and followed up in Haseki Training and Research Hospital Ear, Nose and Throat Clinic between January 2004 and October 2007 was evaluated. The demographic data of the patients, tumor localization sites, surgical techniques, TNM stages and regional neck metastases were evaluated. In laryngeal cancer patients, metastatic lymph nodes were found in 36 of 83 (43%) neck specimens. Patients with intraoral tumors had metastases in six (36.4%) of 20 neck specimens. In hypopharynx tumor patients in six of seven (85.7%) showed metastasis. These results suggest that elective neck treatment in patients with head and neck squamous cell cancers, should include neck levels I, II, III, IV and V. Upper aerodigestive system squamous cell cancers have specific patterns of invasion in cervical region. According to the localization of the primary tumor, high risk sites of metastases were detected. Selective neck dissections were planned according to these invasion patterns of tumors.

  19. 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 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.

  20. Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia.

    Science.gov (United States)

    Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Paiva, Carlos Eduardo; Barroso, Eliane Marçon; Camargos, Mayara Goulart de; Tsunoda, Audrey Tieko; Longatto-Filho, Adhemar; Paiva, Bianca Sakamoto Ribeiro

    2017-01-01

    To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language. A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term "pelvic area". The question CD5, "I worry about spreading the infection", was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil

  1. Laser CO2 vaporization for high-grade cervical intraepithelial neoplasia: a long-term follow-up series.

    Science.gov (United States)

    Fallani, Maria Grazia; Penna, Carlo; Fambrini, Massimiliano; Marchionni, Mauro

    2003-10-01

    The goal of this study was to evaluate the effectiveness of laser CO(2) vaporization for conservative treatment of ectocervical high-grade cervical intraepithelial neoplasia (CIN) particularly by the evaluation of the reappearance risk of disease in long-term follow-up. One hundred fifty-nine patients were submitted to CO(2) laser vaporization for high-grade CIN and followed up for a minimum of 5 years. Selection of cases, depth of ablation, complications, and cure rate (percentage of treated patients in whom there was no recurrent/persistent high-grade CIN at the 5-year follow-up examination) were retrospectively evaluated. Selected cases for colposcopy were submitted to a 6-mm mean depth of vaporization without intra- or postoperative complications. The cure rate for a single treatment was 97.5% and a satisfactory colposcopic follow-up was possible in 99.4% of treated patients. No case of invasive carcinoma occurred after a mean follow-up of 7.1 years. Four cases (2.5%) were high-grade CIN persistence observed after a mean time of 3.75 months, suggesting incomplete destruction of the deepest part of the lesion involving the glandular crypt base. Long-term follow-up proves that laser CO(2) vaporization still has a place in the treatment of CIN. In selected cases it represents a safe alternative for conization in the treatment of high-grade CIN, but colposcopic expertise is essential for adequate preoperative selection of cases.

  2. HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia.

    Science.gov (United States)

    Ho, G Y; Kadish, A S; Burk, R D; Basu, J; Palan, P R; Mikhail, M; Romney, S L

    1998-10-29

    Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intraepithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high-grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for 10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high-grade lesions and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high-grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV-infected cells toward neoplastic progression.

  3. Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Giannella, Luca; Fodero, Cristina; Boselli, Fausto; Rubino, Teresa; Mfuta, Kabala; Prandi, Sonia

    2017-04-01

    To assess the effect of age on pre- and post-conization HPV genotype distribution. The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (related changes in the HPV genotypes present were evaluated. There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030). The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence. © 2017 International Federation of Gynecology and Obstetrics.

  4. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China)

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  5. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Esajas, MD; Duk, JM; de Bruijn, HWA; Aalders, JG; Willemse, PHB; Sluiter, W; Pras, B; ten Hoor, K; Hollema, H; van der Zee, AGJ

    2001-01-01

    Purpose: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. Patients and Methods: Follow-up data were evaluated in patients with early-stage squamous cell cervical

  6. Quantitative Histopathological Analysis of Cervical Intra-Epithelial Neoplasia Sections: Methodological Issues

    Directory of Open Access Journals (Sweden)

    Martial Guillaud

    2004-01-01

    Full Text Available Objectives: As part a Program Project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analysis of biopsies from 1800 patients. Several methodological issues have arisen with respect to this analysis: (1 Finding the most efficient way to compensate for staining intensity variation with out losing diagnostic information; (2 Assessing the inter‐ and intra‐observer variability of the semi‐interactive data collection; and (3 the use of non‐overlapping cells from the intermediate layer only. Methods: Non‐overlapping quantitatively stained nuclei were selected from 280 samples with histopathological characteristics of normal (199, koilocytosis (37, CIN 1 (18, CIN 2 (10 and CIN 3 (16. Linear discriminant analysis was used to assess the diagnostic information in three different feature sets to evaluate and compare staining intensity normalization methods. Selected feature values and summary scores were used to evaluate intra‐ and inter‐observer variability. Results: The features normalized by the internal subset of the imaged cells had the same discriminatory power as those normalized by the control cells and by both normalization methods seem to have additional discriminatory power over the set of features which do not require normalization. The use of the internal subset decreased the image acquisition time by ∼50% at each center, respectively. The intra‐ and inter‐observer variability was of a similar size. Good performance was obtained by measuring the intermediate layer only. Conclusion: The use of intensity normalization from a subset of the imaged non‐overlapping intermediate layer cells works as well as or better than any of the other methods tested and provides a significant timesaving. Our intra‐ and inter‐observer variability do not seem to affect the diagnostic power of the data. Although this must be tested in a larger data set, the use of

  7. Relationship of herpes simplex virus type-2 antibodies and squamous dysplasia to cervical carcinoma in situ.

    Science.gov (United States)

    Thomas, D B; Rawls, W E

    1978-12-01

    Serum specimens from 75 women with cervical carcinoma in situ, 84 with squamous dysplasia, and 132 controls, who had previously been interviewed and tested for complement fixing antibodies against a number of organisms, were analyzed for HSV-2 antibodies. Carcinoma in situ and severe dysplasia were associated with HSV-2 antibodies. Mild dysplasia was related to evidence of prior infection by Trichomonas vaginalis, adenoviruses, and Mycoplasma pneumoniae, plus a history of vaginal discharge. Severe dysplasia was less strongly related to these variables. The relative risk of dysplasia increased with the number of different pathogens by which a woman had been infected. It is concluded that HSV-2 may be a cause of carcinoma in situ; that much dysplasia is a nonspecific reaction of the cervical epithelium to chronic inflammation; and that dysplastic lesions that are caused by HSV-2, and hence may be a precursor to carcinoma in situ, tend to be distinguished by their severity.

  8. Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study.

    Science.gov (United States)

    Miranda, Lidyane Neves; Reginaldo, Fernanda Priscila Santos; Souza, Daliana Maria Berenice Oliveira; Soares, Christiane Pienna; Silva, Tarsia Giabardo Alves; Rocha, Keyla Borges Ferreira; Jatobá, Carlos André Nunes; Donadi, Eduardo Antonio; Andrade, Joanlise Marco Leon; Gonçalves, Ana Katherine Silveira; Crispim, Janaína Cristiana Oliveira

    2015-01-01

    Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

  9. Risk factors for cervical intraepithelial neoplasia in HIV-infected women on antiretroviral treatment in Côte d'Ivoire, West Africa.

    Science.gov (United States)

    Jaquet, Antoine; Horo, Apollinaire; Ekouevi, Didier K; Toure, Badian; Coffie, Patrick A; Effi, Benjamin; Lenaud, Severin; Messou, Eugene; Minga, Albert; Sasco, Annie J; Dabis, François

    2014-01-01

    Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1-5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301-621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2-0.6) or ≥200-350 cells/mm3 (OR 0.6; 95% CI 0.4-1.0) (Ref: HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out.

  10. Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis.

    Science.gov (United States)

    Onuki, Mamiko; Matsumoto, Koji; Sakurai, Manabu; Ochi, Hiroyuki; Minaguchi, Takeo; Satoh, Toyomi; Yoshikawa, Hiroyuki

    2016-01-01

    We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; phigh-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

  11. 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

  12. 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

  13. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.

    Science.gov (United States)

    Meyskens, F L; Surwit, E; Moon, T E; Childers, J M; Davis, J R; Dorr, R T; Johnson, C S; Alberts, D S

    1994-04-06

    Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%. This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN. Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test. RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible. A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects. A derivative of vitamin A can reverse or suppress an epithelial

  14. Are the human papillomavirus genotypes different in cervical cancer and intraepithelial neoplasia in Jewish Israeli women, a low-risk population?

    Science.gov (United States)

    Laskov, Ido; Grisaru, Dan; Efrat, Gabi; Trejo, Leonor Leidor; Grisaru, Galia; Avidor, Boaz

    2013-05-01

    Israel is traditionally considered to have the lowest prevalence of cervical cancer compared with that in other countries of the Western world. The aim of the present study was to establish the human papillomavirus (HPV) genotypes distribution among Israeli Jewish women with premalignant and cervical cancer. Fifty-two specimens with invasive cervical cancer and 50 specimens with high-grade cervical intraepithelial neoplasia (CIN2/3) were identified. Human papillomavirus genotyping in paraffin-embedded specimens was performed by deparaffinization of the tissue sections and DNA extraction, followed by HPV genotype detection using a validated polymerase chain reaction (PCR)-based HPV GenoArray test kit, to simultaneously identify 21 HPV genotypes. Forty-eight (48/52; 92.3%) cervical cancer samples demonstrated PCR-amplifiable DNA (non-HPV DNA). Forty (83.3%) of 48 samples were high-risk (HR) HPV positive. Six (12.5%) of 48 patients showed multiple HR HPV infections. Human papillomavirus types 16 and 18 dominated covering 28 (58.3%) and 14 (29.16%) of 48 samples. Human papillomavirus types 16 and 18 coinfected all 6 cases of multiple HR HPV infections. In CIN2/3 samples, 37 (78.7%) of 47 samples demonstrated PCR-amplifiable DNA (non-HPV DNA), and 20 (54.0%) of these 37 samples were infected by HPV. Human papillomavirus type 16 was found in 19 (95.0%) of 20 cases. Human papillomavirus type 18 was found in 3 (15.0%) of 20 cases; hence, HPV16 and HPV18 contributed to 100% of the cases. Human papillomavirus types 16 and 18 were responsible for the vast majority of invasive cervical cancer and CIN2/3 specimens (81.2% and 100%, respectively). Therefore, it is essential to include the HPV vaccine in the vaccine schedule of the Israeli population.

  15. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus

    NARCIS (Netherlands)

    Bergman, Jacques J. G. H. M.; Zhang, Yue-Ming; He, Shun; Weusten, Bas; Xue, Liyan; Fleischer, David E.; Lu, Ning; Dawsey, Sanford M.; Wang, Gui-Qi

    2011-01-01

    Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett's esophagus. To evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate-grade squamous intraepithelial neoplasia (MGIN) and high-grade squamous intraepithelial neoplasia

  16. Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients.

    Science.gov (United States)

    Starita, Noemy; Annunziata, Clorinda; Waddell, Keith M; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2015-01-01

    The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/10(5) cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n = 11) and B2 (n = 6). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions.

  17. Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients

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    Noemy Starita

    2015-01-01

    Full Text Available The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS. Human herpesvirus type 8 (HHV8, has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25% HIV-positive, and in 2 out of 24 (8.3% HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1% PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7% nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/105 cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n=11 and B2 (n=6. This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions.

  18. Cervical dysplasia

    Science.gov (United States)

    ... squamous cells - dysplasia; Pap smear - dysplasia; HPV - dysplasia; Human papilloma virus - dysplasia; Cervix - dysplasia; Colposcopy - dysplasia Images Female reproductive anatomy Cervical neoplasia Uterus Cervical dysplasia - series References American ...

  19. Retracted: Worst Pattern Of Invasion and occult cervical metastases for oral squamous carcinoma.

    Science.gov (United States)

    Velosa, Claudia; Shi, Qiuying; Stevens, Todd M; Chiosea, Simion I; Purgina, Bibiana; Carroll, William; Rosenthal, Eben; Morlandt, Anthony; Loree, Thom; Brandwein-Weber, Margaret S

    2017-03-28

    The above article, published online in Wiley Online Library as the Version of Record on March 28, 2017 (doi 10.1002/hed.24754), has been retracted by agreement between the Editor-in-Chief, Ehab Y. Hanna, and Wiley Periodicals, Inc. The retraction has been agreed owing to a dispute as to authorship and inclusion of some data in the analysis. Velosa, C., Shi, Q., Stevens, T. M., Chiosea, S. I., Purgina, B., Carroll, W., Rosenthal, E., Morlandt, A., Loree, T. and Brandwein-Weber, M. S. (2017), Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck. doi:10.1002/hed.24754. © 2017 Wiley Periodicals, Inc.

  20. Greater expression of the human leukocyte antigen-G (HLA-G and interleukin-17 (IL-17 in cervical intraepithelial neoplasia: analytical cross-sectional study

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    Lidyane Neves Miranda

    Full Text Available CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN, but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G, which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17-producing cells (Th17 cells may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

  1. Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer.

    Science.gov (United States)

    Palan, P R; Mikhail, M S; Goldberg, G L; Basu, J; Runowicz, C D; Romney, S L

    1996-01-01

    Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which

  2. Clinical performance of hybrid capture 2 human papillomavirus testing for recurrent high-grade cervical/vaginal intraepithelial neoplasm in patients with an ASC-US Papanicolaou test result during long-term posttherapy follow-up monitoring.

    Science.gov (United States)

    De Vivar, Andrea Diaz; Dawlett, Marilyn; Wang, Jian-Ping; Jack, Annie; Gong, Yun; Staerkel, Gregg; Guo, Ming

    2015-02-01

    Women who have been treated for high-grade cervical or vaginal intraepithelial neoplasia (CIN or VAIN) or invasive carcinoma are at risk for recurrent/persistent disease and require long-term monitoring. The role of human papillomavirus (HPV) testing in this setting is unclear. To evaluate the clinical performance of the Hybrid Capture 2 (HC2) HPV test for recurrent/residual high-grade CIN or VAIN in patients with a posttherapy abnormal squamous cells of undetermined significance (ASC-US) Papanicolaou test result. We reviewed the follow-up data on 100 patients who had an ASC-US Papanicolaou test and HC2 HPV results after treatment for high-grade CIN/VAIN or carcinoma. Human papillomavirus genotyping was performed for women with a negative HC2 result whose follow-up biopsy revealed CIN/VAIN 2+. The patients' mean age was 47 years. The HC2 test result was positive in 33% of the patients. Follow-up biopsy was available for 17 of these patients (52%) and for 25 of the 67 patients (37%) with a negative HC2 result. A total of 5 of the patients (29%) with a positive HC2 result and 2 of the patients (8%) with a negative HC2 result had CIN/VAIN 3 on follow-up biopsy, a statistically insignificant difference (P = .10). Human papillomavirus 16/18 genotypes were detected in the CIN/VAIN 2+ lesions of 5 patients with a negative HC2 result. HC2 yielded a false-negative rate of 8% for CIN 3. HC2 testing therefore may not be sufficient for triage of patients with an ASC-US Papanicolaou test result. Patients with ASC-US during long-term posttherapy follow-up need close monitoring, with colposcopic evaluation if clinically indicated.

  3. Value of Nucleolar Organizer Regions count in cervical pathology

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    Shiva Raj KC

    2012-03-01

    Full Text Available Background: ‘AgNOR’ represents Nucleolar Organiser Regions stained with silver which are related to cell proliferation rate and tumor malignant potential. The objective of this study was to evaluate the role of AgNOR in differentiating benign and precancerous lesions from cancerous lesions in both cervical smears and histology. Materials and Methods: This was a prospective study conducted at Manipal Teaching Hospital, from July 2005 to June 2007. Women of suspected cervical pathology and who underwent pap smears test followed by subsequent biopsy were included. There were 53 cases were included out of which 11 cases were of high grade squamous intraepithelial lesion and 12 cases of low grade squamous intraepithelial lesion, and 10 cases each of carcinoma, chronic cervicitis with and without squamous metaplasia. Results: In Low grade squamous intraepithelial lesion meanAgNOR dots was < (2.9 in pap smears and 1.9 in histology in high grade lesion (3.45 in pap smears and 3.00 in histology. In carcinoma meanAgNOR dots was 5.18 and 4.05 in pap smears and histology respectively. Subjective AgNOR Pattern Assessment in pap smears and in histology was increasing with significant difference from intraepithelial lesions to carcinoma. Conclusion: In cervical pathology, the number and shape of AgNOR dots change from benign to precancerous to malignant tumors. Similarly, AgNOR Pattern Assessment is useful in differentiating benign to intraepithelial lesions to carcinoma cases. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6017 JPN 2012; 2(3: 180-185

  4. Recurrence/persistence of cervical intraepithelial neoplasia after undergoing a LEEP conization at Instituto Nacional de Enfermedades Neoplásicas

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    Gino Venegas-Rodríguez

    2017-01-01

    Full Text Available Objective: To determine the incidence of recurrence/persistence of cervical intraepithelial neoplasia (CIN in patients who underwent a loop electrosurgical excision procedure (LEEP at the Department of Gynecologic Oncology of Instituto Nacional de Enfermedades Neoplásicas (INEN. Materials and methods: A retrospective cohort study in which medical records of patients who underwent a LEEP conization from January 2002 to December 2003 were examined. After the LEEP conization, patients were divided into two groups: one with positive margin and another one with negative margin. Follow-up was performed every 3 months and consisted of a physical examination, Pap test and colposcopy. The outcome was recurrence of CIN. To assess the risk of CIN recurrence among the study groups, relative risk (RR and its respective 95% confidence interval (CI were calculated. Results: A total of 451 patients underwent a LEEP conization during the study period. The mean age was 35.32 years old, the mean number of sexual partners was 2.1 and the mean number of children was 2.7. One hundred and nine (109 patients (25% showed a positive margin and 342 (75% showed a negative one. Out of these subjects, only 94 and 102, respectively, met the eligibility criteria and were followed. The mean follow-up period was 21.74 months. The incidence of recurrence/persistence in patients with positive margin was 5.5%, while the incidence of recurrence/persistence in the group of patients with negative margin was 1.96%. We found no significant differences in the risk of CIN recurrence in the group of patients with positive margin versus patients with negative margin. RR = 2.7, 95% CI (0.41 to 33.8. Conclusion: There was no significant difference in the incidence of cervical intraepithelial neoplasia between patients with positive margin and patients with negative margin.

  5. Viral DNA load of high-risk human papilloma virus is closely associated with the grade of cervical lesions.

    Science.gov (United States)

    Shen, Guqun; Cheng, Jingxin; Wang, Yan; Zhou, Ping; Zhang, Guoqing

    2014-01-01

    This study is to explore the correlation between the viral load of high-risk human papilloma virus (HPV) and the degree of cervical lesions, as well as the follow-up monitoring role of high-risk HPV measurements in the treatment of patients with cervical lesions. Hybrid capture-2 method was used to measure the amount of high-risk HPV load of 361 patients who were enrolled from January 2009 to December 2010 at the Affiliated Tumor Hospital of Xinjiang Medical University, including 76 cases of cervical squamous carcinoma, 119 cases of cervical intraepithelial neoplasia and 166 cases of cervicitis. The correlation between the viral load of high-risk HPV and the degree of cervical lesions was analyzed using correlation analysis. Patients with cervical intraepithelial neoplasia (CIN) and cervical squamous carcinoma were followed up until December 2013, with the follow-up time being 37-60 months. Statistically significant differences in the high-risk HPV load existed between cervicitis group, CIN group and cervical squamous carcinoma group (P = 0.000). In addition, the viral load was increased with the increase of the severity of cervical lesions, showing a positive correlation (r = 0.436, P = 0.000). During the follow-up, 6 cases of vaginal intraepithelial neoplasia, 3 cases of recurrence CIN and 1 case of vaginal squamous cell carcinoma of the vulva were found, which were shown to relate with the continuing high-risk HPV infection in vagina. Viral load of high-risk HPV were positively correlated with the severity of cervical lesions, playing an important role in the monitoring of patients with cervical lesions after treatment.

  6. Long-Lasting Increased Risk of Human Papillomavirus-Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study.

    Science.gov (United States)

    Ebisch, Renée M F; Rutten, Dominiek W E; IntHout, Joanna; Melchers, Willem J G; Massuger, Leon F A G; Bulten, Johan; Bekkers, Ruud L M; Siebers, Albert G

    2017-08-01

    Purpose The aim of this study was to determine the risk of human papillomavirus (HPV)-related carcinomas and premalignancies in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3). Knowledge of this risk is important to preventing the development and progression of other HPV-related premalignancies and carcinomas, by considering prophylactic HPV vaccination and/or by paying increased attention to other HPV-related carcinomas and premalignancies when CIN3 is identified. Methods Women diagnosed with a CIN3 between 1990 and 2010 were identified from the Dutch nationwide registry of histopathology and cytopathology (PALGA) and matched with a control group of women without CIN3. Subsequently, all cases of high-risk (hr) HPV-associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015 were extracted. Incidence rate ratios were estimated for carcinomas and premalignancies of the vulva, vagina, anus, and oropharynx. Results A total of 178,036 women were identified: 89,018 with a previous diagnosis of CIN3 and 89,018 matched control subjects without a history of CIN3. Women with a history of CIN3 showed increased risk of HPV-related carcinomas and premalignancies, with incidence rate ratios of 3.85 (95% CI, 2.32 to 6.37) for anal cancer, 6.68 (95% CI, 3.64 to 12.25) for anal intraepithelial neoplasia grade 3, 4.97 (95% CI, 3.26 to 7.57) for vulvar cancer, 13.66 (93% CI, 9.69 to 19.25) for vulvar intraepithelial neoplasia grade 3, 86.08 (95% CI, 11.98 to 618.08) for vaginal cancer, 25.65 (95% CI, 10.50 to 62.69) for vaginal intraepithelial neoplasia grade 3, and 5.51 (95% CI, 1.22 to 24.84) for oropharyngeal cancer. This risk remained significantly increased, even after long-term follow-up of up to 20 years. Conclusion This population-based study shows a long-lasting increased risk for HPV-related carcinomas and premalignancies of the anogenital and oropharyngeal region after a CIN3 diagnosis. Studies that

  7. Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Jiao, Shun [Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou (China); Li, Xin [Department of Obstetrics and Gynaecology, RenMin Hospital of Wuhan University, Wuhan (China); Banu, Hasina; Hamal, Shreejana [Department of Clinical Medicine, Medical School of Yangtze University, Jingzhou (China); Wang, Xianrong, E-mail: Dr.XianRong.Wang@hotmail.com [Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou (China)

    2015-11-06

    Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration of treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer. - Highlights: • We repurposed the antibiotic drug tigecycline for cervical cancer treatment. • Tigecycline is effectively against cervical cancer cells in vitro and in vivo. • Combination of tigecycline and paclitaxel is synergistic in targeting Hela cells. • Tigecycline acts on Hela cells through inhibiting Wnt/β-catenin signaling.

  8. Past cervical intraepithelial neoplasia grade 3, obesity, and earlier menopause are associated with an increased risk of vulval cancer in postmenopausal women.

    Science.gov (United States)

    Coffey, Kate; Gaitskell, Kezia; Beral, Valerie; Canfell, Karen; Green, Jane; Reeves, Gillian; Barnes, Isobel

    2016-08-23

    Vulval cancer predominantly affects postmenopausal women. A smaller proportion of vulval cancers, particularly at older ages, are now thought to be associated with human papillomavirus infection than previously reported, but other risk factors have not been well examined in prospective cohort studies. A total of 1.3 million women aged 49-65 years were followed for incident vulval cancer (ICD-10 C51). Adjusted Cox regression models were used to examine the relationship between reproductive and lifestyle factors and risk of vulval cancer. There were 898 vulval cancers registered in the cohort over an average of 14 years of follow-up; 70% were squamous cell carcinomas. Past registration of cervical carcinoma in situ (RR 2.68; 95% CI 1.71-4.18; Pobesity (RR 1.71; 95% CI 1.44-2.04; Pcancer. Past cervical pre-cancer, obesity, and earlier age at menopause are associated with an increased risk of vulval cancer at older ages.

  9. 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

    is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a......) 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...... conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P INK4a...

  10. CERVICAL INTRAEPITHELIAL NEOPLASIA TREATMENT. ANALYSIS OF THE DATA OF THE PATIENTS TREATED AT DEPARTMENT OF GYNECOLOGY AND OBSTETRICS IN LJUBLJANA DURING 1996–2000

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    Mili Lomšek

    2003-12-01

    Full Text Available Background. Successful diagnosis and management of cervical intraepithelial neoplasia (CIN prevent the occurrence of invasive cervical cancer, which is one of the important indicators of the national health care.Methods. The retrospective analysis studies patients at Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, who had in the period from January 1996 to December 2000 cervical biopsy due to CIN suspicion, based on abnormal PAP smear test and/or abnormal colposcopy. The patients, whose CIN diagnosis was confirmed with cervical biopsy sample histology, were treated by local methods (laser vaporisation, laser conization, large loop excision of the transformation zone (LLETZ, cold-knife conization, hysterectomy or just supervised with 4–6 month PAP smear and colposcopy follow-up. Our efficiency criteria were PAP smear one year after the treatment and excised tissue histology (for local excision methods and hysterectomy. We also compared the histology of the cervical biopsy sample and the excised tissue after excision methods of treatment and hysterectomy. The sources of our database were the patients’ records.Results. The study analyses 800 patients. In 195 women (24% CIN wasn’t confirmed by cervical biopsy sample histology. In the remaining 605 patients (76%, we diagnosed severe dysplasia (CIN III in 332 women (55%, moderate dysplasia (CIN II in 153 women (25% and light dysplasia (CIN I in 120 women (20%. CIN was most frequently diagnosed in the age between 30 and 34. CIN III was most frequently treated with cold-knife conization and CIN II with laser vaporisation. We also treated 120 patients (66% with CIN I, mostly with laser vaporisation. There were no substantive differences in therapeutic efficacy between the methods of treatment. Besides hysterectomy, the most successful method was cold-knife conization in 96,9%, and the least successful LLETZ in 91,7%. The histology between cervical biopsy sample and

  11. [Uterine cervical carcinoma and human papillomaviruses].

    Science.gov (United States)

    Sugase, M

    1992-06-01

    For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer.

  12. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in men who have sex with men infected with HIV.

    Science.gov (United States)

    Sendagorta, Elena; Romero, Maria P; Bernardino, Jose I; Beato, María J; Alvarez-Gallego, Mario; Herranz, Pedro

    2015-08-01

    Currently, screening for anal high-grade squamous intraepithelial lesions (anal HSIL) relies on anal cytology and high-resolution anoscopy. Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM infected with HIV, in comparison to DNA-HR-HPV and anal cytology. This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by means of the CLART® HPV2 assay (GENOMICA S.A.U., Madrid, Spain). E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33, and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy ĺEtoile, France). HR-HPV DNA and HPVE6/E7 mRNA were detected in 82% and 57% of the anal smears respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared to 100%, 31.5%, 55.4%, and 100% for HR-HPV-DNA testing and to 83%, 40.7%, 54.9%, 73.3% of cytology testing. In comparison with the other tests, HPVE6/E7 mRNA testing yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM infected with HIV. © 2015 Wiley Periodicals, Inc.

  13. The terminology of pre-invasive cervical lesions in the UK cervical screening programme.

    Science.gov (United States)

    Herrington, C S

    2015-12-01

    The terminology of non-invasive epithelial abnormalities associated with an elevated risk of having or developing invasive cervical carcinoma (pre-invasive lesions) has been modified frequently over time as understanding of the underlying biology, and approaches to disease management, have changed. The arguments are now converging on the conclusion that the most appropriate terminology for cervical squamous intraepithelial abnormalities should be two-tier rather than three-tier. Given the findings of the Lower Anogenital Squamous Terminology (LAST) project in the USA, which have recently been endorsed by the World Health Organisation classification of tumours of female reproductive organs, the recommended terms are low-grade and high-grade squamous intraepithelial lesion (SIL), with the option of including the relevant cervical intraepithelial neoplasia (CIN) grade in parentheses. Although, at first sight, this appears to represent only a small change, there is a fundamental conceptual difference between the systems. The CIN system requires, first, the identification of a CIN lesion and, second, the determination of its grade on a continuum, with subsequent division into three grades. The SIL system is based on the existence of two different forms of human papillomavirus (HPV) infection, with productive infection leading to low-grade SIL and transforming infection leading to high-grade SIL. © 2015 John Wiley & Sons Ltd.

  14. Clinical results of the liquid-based cervical cytology tool, Liqui-PREP, in comparison with conventional smears for detection of squamous cell abnormalities.

    Science.gov (United States)

    Canda, M Tunc; Demir, Namik; Sezer, Orcun; Doganay, Latife; Ortac, Ragip

    2009-01-01

    To compare the adequacy and efficacy of the liquid-based cytology tool Liqui-PREP (LP) with the conventional Papanicolaou smear (CS) test, for the screening of squamous cell abnormalities. Data for 2,000 subjects screened with CS and 4,000 different subjects screened with the LP test were compared. LP showed significant decrease in the rate of unsatisfactory smears (P<0.01) and the detection rate for atypical squamous cells was significantly higher (P<0.01). The rate of low-grade squamous intraepithelial lesion was also higher, but this did not reach statistical significance. The number of high-grade squamous intraepithelial lesions detected was increased with LP, and the histological correlation of LSIL lesions showed a higher positive-predictive value. The coexistence of abnormal colposcopic findings with abnormal smear results was higher for LP (P<0.004). Furthermore, high-risk HPV-DNA detection was found to be increased in atypical LP smears than in normal LP smears. The liquid-based cytology tool LP detected more squamous cell lesions than CS. Also it reduced the number of unsatisfactory results due to enhanced cell visualization, and improved screening for HPV-DNA.

  15. Elimination of high-risk human papillomavirus type HPV16 infection by 'Praneem' polyherbal tablet in women with early cervical intraepithelial lesions.

    Science.gov (United States)

    Shukla, Shirish; Bharti, Alok C; Hussain, Showket; Mahata, Sutapa; Hedau, Suresh; Kailash, Uma; Kashyap, Veena; Bhambhani, Suresh; Roy, Meera; Batra, Swaraj; Talwar, G P; Das, Bhudev C

    2009-12-01

    'Praneem', a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16. Twenty women molecularly diagnosed positive for HPV16 infection without or with low grade squamous intraepithelial lesion (LSIL) or inflammation were assigned to receive intra-vaginal, topical application of either Praneem tablet or placebo for 30 days excluding the days of menstrual period and were evaluated for persistence of HPV infection using HPV L1 consensus and HPV type 16-specific PCR as primary outcome. One course of Praneem treatment resulted in elimination of HPV in 6 out of 10 (60%) cases. A repeat treatment of four patients with persisting HPV infection resulted in clearance of HPV in two additional cases resulting in an overall 80% clearance of HPV 16 as against a spontaneous clearance of 10% (1/10) seen in the placebo arm. The elimination of HPV DNA was found to be accompanied by marked improvement in clinical symptoms and cytological abnormalities of Praneem-treated patients. Our results showed for the first time that a 30-day intra-vaginal application of the Praneem can result in elimination of HPV infection from the uterine cervix.

  16. Cancer of the vulva in a 25-year-old woman with VIN III and high-grade cervical SIL--case report.

    Science.gov (United States)

    González-Bosquet, E; Sunol, M; Hernandez, A; Callejo, J; Lailla, J M

    2007-01-01

    Human papillomavirus (HPV) infection is associated with an increase in intraepithelial lesions of the genital tract which are often multicentric. Following is a presentation of a case of vulvar cancer in a young woman (25 years of age) with multiple vulvar intraepithelial neoplasia (VIN III) lesions, a high-grade squamous intraepithelial cervical lesion, and a HPV type 16 infection at high risk of oncogenic transformation. This case offers an opportunity to discuss the risk factors that may favor the appearance of these lesions in young women, and their clinical management, diagnosis, and treatment.

  17. 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.

  18. Applicability of preoperative nuclear morphometry to evaluating risk for cervical lymph node metastasis in oral squamous cell carcinoma.

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    Masaaki Karino

    Full Text Available BACKGROUND: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma. METHODS: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio, and nuclear area coefficient of variation (NACV. Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis. RESULTS: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in node-negative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site. CONCLUSION: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma.

  19. Long-term results of the combined modality therapy for advanced cervical metastatic head and neck squamous cell carcinoma.

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    Preuss, S F; Klussmann, J P; Wittekindt, C; Damm, M; Semrau, R; Drebber, U; Guntinas-Lichius, O

    2007-04-01

    A consensus treatment strategy for advanced cervical metastatic head and neck squamous cell carcinoma has not been established. The aim of this retrospective study was to investigate the outcome of these patients uniformely using a strategy which consists of surgery for the primary tumor and the neck metastases followed by postoperative radio(chemo)therapy. We included a selected series of 518 patients with previously untreated head and neck squamous cell carcinoma. The overall survival (OS), the disease specific survival (DSS), the disease free survival (DFS), the local control (LC) and regional control (RC) estimates were calculated. The statistical relationship of various clinical and histopathological variables on the above mentioned estimates were analyzed. The overall survival probability was 73.2% for pN0 stage, 43% for pN>1 stages and 31% for pN2c/pN3 stages. The pN stage significantly influenced the survival probabilities in oropharyngeal (p=0.0001) and laryngeal tumors (p<0.0001) in univariate analyses. In multivariate analysis, age, pT stage, pN stage, M stage, and extranodal spreading were independent risk factors for decreased disease-specific survival. We could show that pN stage is an important independent prognostic factor in head and neck cancer. The presented multimodal treatment protocol provides excellent oncological outcomes and should therefore be standard of care for patients with operable advanced cervical metastatic head and neck squamous cell carcinoma.

  20. Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

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    Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

    2014-02-01

    Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

  1. High-grade cervical intraepithelial neoplasia in human papillomavirus self-sampling of screening non-attenders

    DEFF Research Database (Denmark)

    Lam, J U H; Elfström, K M; Ejegod, D. M.

    2017-01-01

    BACKGROUND: Self-sampling for human papillomavirus (HPV) offered to women who do not participate in cervical cancer screening is an increasingly popular method to increase screening coverage. The rationale behind self-sampling is that unscreened women harbour a high proportion of undetected...

  2. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, M. P.; van Leeuwen, A. M.; Hollema, H.; Quint, W. G.; Pieters, W. J.

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  3. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  4. Role of active and passive smoking in high-risk human papillomavirus infection and cervical intraepithelial neoplasia grade 2 or worse.

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    Feng, Rui Mei; Hu, Shang Ying; Zhao, Fang Hui; Zhang, Rong; Zhang, Xun; Wallach, Asya Izraelit; Qiao, You Lin

    2017-09-01

    We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999-2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10-1.91), for hr-HPV infection and 1.89 (95% CI=1.03-3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00-1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14-2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02-3.88) risk of CIN2+. Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+.

  5. Enzyme-linked immunosorbent assay for p16(INK4a) - a new triage test for the detection of cervical intraepithelial neoplasia?

    Science.gov (United States)

    Jentschke, Matthias; Lange, Victoria; Soergel, Philipp; Hillemanns, Peter

    2013-02-01

    To evaluate enzyme-linked immunosorbent assay (ELISA) for cyclin-dependent kinase inhibitor 2A protein (p16(INK4a) ) on self-collected cervicovaginal lavage samples as an additional triage test to identify women with high-grade cervical intraepithelial neoplasia (CIN). Retrospective feasibility, sensitivity and specificity study. University Medical School, Germany. One hundred and fifty-two patients from the colposcopy clinic were included. All women used a cervico-vaginal lavage device (Delphi Screener) for self-sampling and had gynecological examinations with Pap smears, cervical smears in ThinPrep PreservCyt solution and Cervatec medium for human papillomavirus (HPV) testing (Qiagen Hybrid Capture 2) and colposcopic examinations with biopsies if abnormalities were detected (72 women; 51%). All cytological samples were examined by p16(INK4a) ELISA. Sensitivity and specificity of p16(INK4a) ELISA for high-grade CIN. Complete data were available for 140 women. Among these, 62 women (46%) presented with an atypical Pap smear and 65 (46.4%) were high-risk HPV positive in the reference smear sample. Seventeen women (12%) had CIN 3+. Twenty-seven (19%) physician-collected samples were p16(INK4a) ELISA positive. In contrast, p16(INK4a) ELISA turned out to be positive in only one (1%) vaginal lavage sample. Our study shows that self-sampling with cervicovaginal lavage followed by p16(INK4a) ELISA is not suitable for the detection of high-grade CIN. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  6. Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions.

    Science.gov (United States)

    Bottari, F; Sideri, M; Gulmini, C; Igidbashian, S; Tricca, A; Casadio, C; Carinelli, S; Boveri, S; Ejegod, D; Bonde, J; Sandri, M T

    2015-07-01

    Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3.

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    Vlastos, Anne-Thérèse; West, Loyd A; Atkinson, E Neely; Boiko, Iouri; Malpica, Anais; Hong, Waun K; Follen, Michele

    2005-01-01

    Our purpose was to conduct a double-blinded randomized trial of difluoromethylornithine (DFMO) at 0.125, 0.5 gm/m2, versus placebo in the treatment of cervical intraepithelial neoplasia (CIN) grades 2 to 3. A promising phase I study has shown histopathologic responses at these dose levels. Patients with histopathologically confirmed CIN 2-3 lesions were recruited from a colposcopy clinic and underwent Papanicolaou testing, human papillomavirus testing, and colpophotography. They took oral contraception and DFMO or placebo elixir for 28 days and filled out the National Cancer Institute common toxicity calendars. They returned for follow-up and a repeat Papanicolaou smear, colpophotograph, and loop excision of the cervix. There were no statistically significant differences among the arms in histopathologic response. This could no be explained by any biases in risk factors. The prominent toxicities were diarrhea, dizziness, nausea, and headaches. There were no differences in the toxicities among arms. The Papanicolaou smear was a poor biomarker of response and correlated poorly with the histopathology. DFMO is no active at 0.125 and 0.5 gm/m2 for 28 days when given orally in CIN 2-3. Higher oral doses or longer administration is necessary, supporting data from breast trials. Alternatively, a trial of topical DFMO might merit attention as activity has been noted in trials of actinic keratoses.

  8. Efficacy of human papillomavirus l1 protein vaccines (cervarix and gardasil in reducing the risk of cervical intraepithelial neoplasia: A meta-analysis

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    Mohammad Reza Haghshenas

    2017-01-01

    Full Text Available Human papillomavirus (HPV can induce cervical intraepithelial neoplasia (CIN. Vaccination against HPV can play an important role in CIN prevention. This study aims to estimate the efficacy of L1 protein vaccines (Cervarix and Gardasil in CIN 1, 2, 3 risk reduction using meta-analysis. Relevant articles were identified by two independent researchers searching international databanks. After application of inclusion/exclusion criteria and quality assessment, eligible articles were entered into the final meta-analysis. Inverse variance method and fixed effect model were used to combine the results of the primary studies. The heterogeneity between the results was assessed using Cochrane and I2 indices. Of 11,530 evidence identified during the primary search, three papers were found eligible for meta-analysis, including 7213 participants in the intervention groups and 7170 healthy controls. The efficacy (95% confidence interval of HPV 6, 11, 16, 18 monovalent and quadrivalent vaccines against CIN 1, CIN 2, and CIN 3 were estimated as of 95% (88–98, 97% (85–99, and 95% (78–99, respectively. This study showed that L1 protein vaccines Cervarix and Gardasil are highly protective vaccines playing an effective role in the prevention of HPV 6, 11, 16, 18 which are responsible for CIN 1, CIN 2, and CIN 3.

  9. Human papillomavirus infection-associated markers of the occurrence and progression of cervical intraepithelial neoplasias: from research developments to clinical practice

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    L. I. Korolenkova

    2010-01-01

    Full Text Available Cervical intraepithelial neoplasias (CIN, the stages of development in cancer of the cervix uteri (CCU during persisting infections caused by human papillomavirus (HPV, are a disease frequently occurring in young women. The carcinogenic process lasts 3-5 to 10-30 years during which timely detection and organ-saving treatment for the lesion are possible. The development of markers for the persis- tence of HPV infection and the transition of a productive to transforming phase of infection (from mild to severe CIN is a basis for the current approach to screening for CIN and BC and to a patient follow-up. The review paper presents the main areas of studies developing markers that are directly associated with HPV infection (HC2 viral load, virus typing, viral physical status, E6 and E7 mRNA, E2/E6 ratio and its mediated action on host cells (p16INK4a, hTERT. The pathogenetic effect of HPV early genes and their association with the expression of basic surrogate markers are considered in detail. The majority of the presented markers are being actively put into clinical practice in foreign countries.

  10. Vulvar intraepithelial neoplasia.

    Science.gov (United States)

    Preti, Mario; Scurry, James; Marchitelli, Claudia E; Micheletti, Leonardo

    2014-10-01

    Vulvar intraepithelial neoplasia (VIN) is a high-grade intraepithelial squamous lesion and precursor of invasive squamous cell carcinoma (SCC). The 2004 International Society for the Study of Vulvovaginal Disease (ISSVD) classification distinguished two types of VIN: usual type (human papillomavirus (HPV)-related) and differentiated type (not HPV-related). The incidence of usual-type VIN is higher in younger women, while differentiated-type VIN is more common in older patients with chronic dermatologic conditions. Differentiated-type VIN has a greater invasive potential and shorter time between diagnosis and SCC than usual-type VIN. The diagnosis of VIN is carried out by identifying a lesion by visual inspection and confirming by performing a biopsy. Screening tests are not available. Patients with usual-type VIN are at a higher risk of developing another HPV-related malignancy of the anogenital tract; therefore, examination from the cervix to the perianal area is mandatory. The therapeutic approach to VIN balances the invasive potential with the need to be as conservative as possible. Current prophylactic HPV vaccines offer protection against usual-type VIN and related invasive carcinoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. [Prevalence of epithelial squamous cell abnormalities and associated factors in women of a rural town of Colombia].

    Science.gov (United States)

    Grisales, Hugo; Vanegas, Angela Patricia; Gaviria, Angela M; Castaño, Jorge; Mora, Martín Alonso; Borrero, Mauricio; Rojas, Carlos; Arbeláez, María Patricia; Sánchez, Gloria I

    2008-06-01

    In spite of implementation of cytology-based cervical cancer screening in Colombia, mortality rates remain stable. The description of factors associated to cervical pre-neoplasic lesions is needed to establish strategies for mortality prevention. The prevalence of epithelial squamous cell abnormalities was determined to explore the association of cytology abnormalities with described risk factors. This population-based, cross-sectional study included 739 women randomly selected by age. A validated face-to-face questionnaire and conventional cervical cytology were used to collect the information. To establish the association between cervical abnormalities and some qualitative variables, the independent chi squared test was used. We also calculated prevalence ratio with their 95% confidence intervals. A logistic regression model was used to explore variables that potentially explain cytology abnormalities. The prevalence of squamous cell abnormality was 15.8%. Among women with abnormal cytology, 10% presented atypical squamous cells of undetermined significance, 3.9% low grade squamous intra-epithelial lesion and 1.9% high grade squamous intra-epithelial lesion. The adjusted logistical regression analysis showed that history of sexual transmitted disease, two or more sexual partners during entire life and previous abnormal cytology were associated with cytology abnormalities. The relation of epithelial squamous cell abnormalities with sexual behavior history reflexes the link between human papiloma virus infection and cervical cancer pre-neoplasic lesions. The frequency of use and knowledge about the purpose of cytology were factors that suggested other diagnostic limitations such as quality of cervical cytology or barriers to access health care. These latter factors may be the underlying basis for the high cervical cancer mortality rates.

  12. The status of cervical cytology in Swaziland, Southern Africa: A descriptive study

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    Okonda Sylvain

    2009-01-01

    Full Text Available Background: Cancer of the cervix is the most common cancer in women in Swaziland where most women never undergo cervical screening. The extremely high prevalence of HIV/AIDS in Swaziland complicates the management of preinvasive and invasive cervical cancer. The purpose of this study was to assess the current status of cervical cytology in Swaziland, its strengths and limitations. Methods: The study is a retrospective review of 12,188 conventional cervical smears received by the Central Public Health Laboratory in Swaziland from June 2004 to May 2006. Results: Review of results showed very high rates of cytologic abnormalities with 43.2% of smears screened reported as abnormal. The percentages of abnormalities were as follows: atypical squamous cells of undermined significance (ASC-US, 19.8%; atypical squamous cells, cannot exclude HSILs (ASC-H, 8.8%; low-grade squamous intraepithelial lesions (LSIL, 9.0%; high-grade squamous intraepithelial lesions (HSIL, 4.6%; squamous cell carcinomas, 0.5%; atypical endocervical cells, 0.6%; and atypical endometrial cells, 0.4%. Just over 5% of smears were inadequate. The highest rates of HSILs and invasive squamous carcinoma occurred in women aged 50-59 years. Conclusions: This study underscores the need to reduce the incidence of cervical cancer and its precursor lesions in Swaziland women. Based on studies of human papillomavirus (HPV types in other Southern African countries, current HPV vaccines would reduce the incidence and mortality from cervical cancer in the future, but cervical screening would still be required, both for women already infected with the HPV and for HPV subtypes not covered by current vaccines. The most cost-effective combination of screening modalities such as visual inspection, HPV DNA testing, and cytology should be investigated. Cervical cancer reduction needs to be managed within the greater framework of the HIV/AIDS epidemic.

  13. Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

    Science.gov (United States)

    Ma, Yuhua; Yang, Jie; Wang, Ruozheng; Zhang, Zegao; Qi, Xiaoli; Liu, Chunhua; Ma, Miaomiao

    2017-01-01

    Background Definitive radiation therapy (RT) (with or without cisplatin-based chemotherapy) is one of the most effective treatments for cervical squamous cell carcinoma (CSCC), but efficacy is limited due to resistance. In the present study, we investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA)and response to RT in patients with CSCC. Methods The expression of Aurora-A in biopsy specimens of untreated primary tumors in 129 Uyghur patients with CSCC was investigated immunohistochemically. Primary treatment in these patients was definitive radical RT, which consisted of pelvic RT plus brachytherapy (total point A dose:70–85 Gy) (with or without cisplatin-based chemotherapy). The prognostic value of tumoral Aurora-A expression and patients’ clinical outcomes were evaluated. Results Aurora-A expression was significantly associated with lymph node metastasis (P<0.001), large tumor size (P<0.001), low hemoglobin (Hb) level (P=0.011) and recurrence (P<0.001), but not other clinicopathological factors. Definitive RT was unfavorable in patients with high Aurora-A expression (P < 0.001). In 129 enrolled patients, lymph node metastasis, large tumor size, low Hb level, and AURKA overexpression were prognostic factors for both recurrent free survival (RFS) and overall survival (OS) in univariate analysis. However, only high AURKA expression was an adverse independent risk factor for both RFS (hazard ratio, 3.953; 95% CI, 1.473-10.638; P = 0.006) and OS (hazard ratio 9.091; 95%CI 2.597-32.258; P<0.001) in multivariate analyses. Conclusions Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance. PMID:28404933

  14. Clinical significance of hTERC gene detection in exfoliated cervical epithelial cells for cervical lesions.

    Science.gov (United States)

    Zheng, Xiuhui; Liang, Peihe; Zheng, Yingru; Yi, Ping; Liu, Qiang; Han, Jian; Huang, Yinhu; Zhou, Yuanguo; Guo, Jianxin; Li, Li

    2013-06-01

    To investigate the clinical significance of abnormal human telomerase RNA gene component (hTERC) gene amplification tested by fluorescence in situ hybridization in cervical lesions. In 373 patients with cytologic abnormalities, high-risk human papilomavirus (HR-HPV) was detected by the hybrid capture II method, and abnormal amplification of the hTERC gene in exfoliated cells was detected by fluorescence in situ hybridization. Cell smear findings suggested atypical squamous cells in 148 patients, low-grade squamous intraepithelial lesion in 62 patients, and high-grade squamous intraepithelial lesion in 107 patients, squamous cell carcinoma in 56 patients, and cervical biopsy-revealed inflammation in 89 patients, cervical intraepithelial neoplasia (CIN) I in 36 patients, CIN II in 43 patients, CIN III in 129 patients, and infiltrating carcinoma in 76 patients. In the inflammation, CIN I, CIN II, CIN III, and infiltrating carcinoma groups, the infection rates of HR-HPV were 29.21%, 52.78%, 74.42%, 92.25%, and 93.42% (P 0.05), but they differed significantly in the sensitivity, specificity, and positive predictive value (P < 0.01). Among the 3 methods, hTERC testing showed the highest specificity and positive predictive value, and HR-HPV testing showed the highest sensitivity. In 41 patients with untreated CIN I and CIN II, the sensitivity of detection of hTERC gene amplification to predict lesion progression was 88.89%, and the specificity was 93.75%. Detection of abnormal amplification of the hTERC gene can assist in screening cervical lesions and identifying CIN I/II patients with a high progression risk.

  15. Ultrastructural localization of human papilloma virus by nonradioactive in situ hybridization on tissue of human cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Multhaupt, H A; Rafferty, P A; Warhol, M J

    1992-01-01

    BACKGROUND: A nonradioactive in situ hybridization was developed to localize human papilloma virus (HPV) at the ultrastructural level. EXPERIMENTAL DESIGN: Cervical biopsies from human uterine cervices clinically suspicious of condyloma were embedded in Lowicryl K4M at low temperature....... Postembedding in situ hybridization was performed with DNA probes specific for HPV types 6/11, 16, and 18. The hybrids were detected by anti-horseradish peroxidase antibodies conjugated with 10 nm colloidal gold particles. RESULTS: Localization for HPV 16 and 18 both was to intranuclear and cytoplasmic sites....... Cytoplasmic detected HPV signals were between masses of intermediate filaments and in vacuoles; other organelles were devoid of positive signal. Within the nucleus the precise localization of the viral nucleic acid was episomal, vacuolar, and chromosomal. In situ hybridization with plasmid control DNA...

  16. Expression of Steroid Hormone Receptors of the Cervix in Cervical Intraepithelial Neoplasia Associated with Human Papillomavirus Infection in Infertile Women

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    E.O. Kindrativ

    2015-01-01

    When studying receptor status of cervical tissue in CIN, there are significant changes in the intensity of ER and PgR receptors expression. Immunohistochemical reaction in terms of identification of estrogen receptors is positive in 29.9 % of cases, negative — in 70.1 %. Positive PgR expression is set in 31.2 % of women with CIN, negative expression — in 68.8 %. In CIN and HPI, the redistribution of steroid receptors expression is marked, since ER is characterized by decrease of epithelial and appearance of stromal positive reaction. PgR expression differs by positive epithelial extinction with expressed nonspecific reaction in stromal component of the cervix. Estimation of hormone-receptor system of the cervix showed a significant decrease (p < 0.05 in ER volume content (twice in comparison with PgR (1.3 times. In CIN associated with HPI, a significant decrease in ER/PgR ratio is noted, with the lowest parameter in the group of patients with CIN-III (p < 0.05. Therefore, detection of the expression of steroid hormone receptors in cervical neoplasia associated with HPI in infertile women can be used as an additional criterion for determining the degree of dysplastic process in cervical epithelium.

  17. Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer Patients.

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    Christina S Fjeldbo

    Full Text Available Hypoxia is an adverse factor in cervical cancer, and hypoxia-related gene expression could be a powerful biomarker for identifying the aggressive hypoxic tumors. Reverse transcription quantitative PCR (RT-qPCR is a valuable method for gene expression studies, but suitable reference genes for data normalization that are independent of hypoxia status and clinical parameters of cervical tumors are lacking. In the present work, we aimed to identify reference genes for RT-qPCR studies of hypoxia in squamous cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia in cervical cancer, i.e. genes regulated by hypoxia in eight cervical cancer cell lines or correlating with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients, were excluded. Among the 182 genes, nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6 that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, were selected for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the optimal set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix and clinical parameters. The suitability of the three reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalization, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (P<0.001, n = 74 and ABrix (P<0.05, n = 32, and the STC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in squamous cervical cancer samples

  18. Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia

    Science.gov (United States)

    Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Paiva, Carlos Eduardo; Barroso, Eliane Marçon; de Camargos, Mayara Goulart; Tsunoda, Audrey Tieko; Longatto-Filho, Adhemar; Paiva, Bianca Sakamoto Ribeiro

    2017-01-01

    ABSTRACT Objective To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) to the Portuguese language. Methods A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. Results The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term “pelvic area”. The question CD5, “I worry about spreading the infection”, was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. Conclusion The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. PMID:28767912

  19. The impact of antiretroviral therapy on HPV and cervical intraepithelial neoplasia: current evidence and directions for future research

    Directory of Open Access Journals (Sweden)

    Sahasrabuddhe Vikrant V

    2010-05-01

    Full Text Available Abstract Increasing numbers of human immunodeficiency virus (HIV-infected women are now accessing life-prolonging highly active antiretroviral therapy (HAART in developing countries. There is a need for better understanding of interactions of human papillomavirus (HPV and HIV, especially in the context of increasing life expectancy due to HAART. The data regarding the impact of HAART on reducing the incidence and progression and facilitating the regression of HPV infection and cervical abnormalities is largely inconsistent. Published studies differ in their study designs (prospective or retrospective cohorts or record linkage studies, screening and diagnostic protocols, duration and type of HAART use, recruitment and referral strategies, and definitions of screening test and disease positivity. Due to the ethical and resource limitations in conducting randomized trials of the impact of HAART on incidence of HPV, CIN, and cervical cancer among HIV-infected women, it is important to consider innovative study designs, including quasi-experimental trials and operations research in sentinel populations to answer the critical research questions in this area.

  20. Development of in-house multiplex real time PCR for human papillomavirus genotyping in Iranian women with cervical cancer and cervical intraepithelial neoplasia.

    Science.gov (United States)

    Sohrabi, Amir; Mirab-Samiee, Siamak; Modarresi, Mohammad Hossein; Izadimood, Narges; Azadmanesh, Kayhan; Rahnamaye-Farzami, Marjan

    2014-01-01

    HPV related cervical cancer as one of the most common women cancers in developing countries. Regarding accessibility of commercial vaccines, any long or short term modality for integrating preventive immunization against HPV in a national program needs comprehensive information about HPV prevalence and its genotypes. The important role of selecting most accurate diagnostic technologies for obtaining relevant data is underlined by different assays proposed in the literature. The main objective of the present study was to introduce an in-house HPV typing assay using multiplex real time PCR with reliable results and affordable cost for molecular epidemiology surveys and diagnosis. 112 samples of formalin fixed paraffin embedded tissues and liquid based cytology specimens from patients with known different grades of cervical dysplasia and invasive cancer, were examined by this method and the result were verified by WHO HPV LabNet proficiency program in 2013. HPV was detected in 105 (93.7%) out of 112 samples. The dominant types were HPV 18 (61.6%) and HPV 16 (42.9%). Among the mixed genotypes, HPV 16 and 18 in combination were seen in 12.4% of specimens. According to acceptable performance, easy access to primers, probes and other consumables, affordable cost per test, this method can be used as a diagnostic assay in molecular laboratories and for further planning of cervical carcinoma prevention programs.

  1. Conservative approach to preneoplastic cervical lesions in postmenopause.

    Science.gov (United States)

    Vetrano, Giuseppe; Aleandri, Vincenzo; Ciolli, Paola; Scardamaglia, Paola; Pacchiarotti, Arianna; Verrico, Monica; Carboni, Simona; Corosu, Roberto

    2008-01-01

    To evaluate the recurrence rate of high-grade squamous intraepithelial lesions in postmenopausal women previously submitted to laser CO2 conization and the role of persistent oncogenic HPV types. Fifty-five patients with a cytological diagnosis of high-grade squamous intraepithelial lesions were triaged with a standard colposcopy. Hormonal replacement therapy was considered as significative in influencing cervical trophism. Vaginal smears for microbiological examination were obtained. H-R HPV test was performed by PCR. The follow-up checks including cytology, colposcopy and HVP test were performed for a minimum of 5 years. Histological analysis revealed 19 CIN2 (cervical intraepithelial lesions) and 36 CIN3 lesions. The cumulative failure rate at first treatment was 14%. HPV test was positive for HPV 16 type in all patients. Forty-two patients during the follow up checks resulted negative to cytology, colposcopy and HR HPV test. At the one-year follow-up check, 7 patients revealed normal cytological and abnormal colposcopical findings and persistent positive HR HPV test. At the five-year follow-up check, 14 patients with a normal cytological smear had a recurrence of CIN2/3 and positive HR HPV test. In postmenopause, the correct management of H-R squamous intraepithelial lesions is still debated. However, a satisfactory follow-up is the main requirement for the conservative management. HPV typing in the follow-up is important to detect persistent types to identify women at risk of developing cervical abnormalities. The incidence of cervical neoplasia does not decrease with increasing age. Since HPV positivity predicted subsequent infection, testing postmenopausal patients for the virus may be a cost-effective method of disease prevention.

  2. Variant-specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia.

    Science.gov (United States)

    Xi, Long Fu; Schiffman, Mark; Koutsky, Laura A; Hughes, James P; Hulbert, Ayaka; Shen, Zhenping; Galloway, Denise A; Kiviat, Nancy B

    2016-09-01

    In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high-risk (HR) variants] compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9-1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants. © 2016 UICC.

  3. The negative predictive value of p16INK4a to assess the outcome of cervical intraepithelial neoplasia 1 in the uterine cervix.

    Science.gov (United States)

    Hariri, Jalil; Øster, Anne

    2007-07-01

    The immunohistochemical expression of p16 in formalin-fixed and paraffin-embedded histological sections was evaluated in a retrospective study comprising a low-grade group of 100 cases of cervical intraepithelial neoplasia (CIN) 1, a high-grade group of 50 cases of CIN 2 to 3, and a benign group of 50 cases of normal tissue or benign lesions in the uterine cervix. The cases were consecutive within each group and had a minimum follow-up period of 5 years. Positive reaction for p16 was detected in all cases in the high-grade group and in only 3 cases in the benign group. In the low-grade group, a total of 9 cases had to be excluded. The remaining 91 cases in the low-grade group showed positive reaction for p16 in 65 cases (71%), including 23 cases that progressed to a high-grade lesion, 36 cases that revealed normal cytological and/or histological picture during the follow-up period, and 6 cases that persisted as CIN 1. A total of 26 cases (29%) in the low-grade group showed negative reaction for p16. All but one of these p16 negative cases in the low-grade group had a benign or normal outcome. This case showed a high-grade lesion in the follow-up period and was probably a high-grade lesion from the beginning and so underestimated as CIN 1. These results reveal that the negative predictive value of p16 to predict the outcome of the cases of CIN 1 is as high as 96%, which strongly suggest an important role of p16 in the assessment of this type of lesion.

  4. Residual Disease and HPV Persistence after Cryotherapy for Cervical Intraepithelial Neoplasia Grade 2/3 in HIV-Positive Women in Kenya

    Science.gov (United States)

    De Vuyst, Hugo; Mugo, Nelly R.; Franceschi, Silvia; McKenzie, Kevin; Tenet, Vanessa; Njoroge, Julia; Rana, Farzana S.; Sakr, Samah R.; Snijders, Peter J. F.; Chung, Michael H.

    2014-01-01

    Objective To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women. Design Follow-up study. Methods 79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells). Results At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4–85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2–15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9–70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively. Conclusions Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity. PMID:25343563

  5. A Non-Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing.

    Science.gov (United States)

    Cremer, Miriam; Paul, Proma; Bergman, Katie; Haas, Michael; Maza, Mauricio; Zevallos, Albert; Ossandon, Miguel; Garai, Jillian D; Winkler, Jennifer L

    2017-03-24

    Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the adapted CryoPen achieved the target depth

  6. Residual disease and HPV persistence after cryotherapy for cervical intraepithelial neoplasia grade 2/3 in HIV-positive women in Kenya.

    Directory of Open Access Journals (Sweden)

    Hugo De Vuyst

    Full Text Available To assess residual cervical intraepithelial neoplasia (CIN 2/3 disease and clearance of high-risk (hr human papillomavirus (HPV infections at 6 months after cryotherapy among HIV-positive women.Follow-up study.79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy and after cryotherapy (cells.At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI: 66.4-85.9. 18 women (22.8% had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2-15.0 among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9-70. The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively.Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.

  7. MicroRNA expression variability in human cervical tissues.

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    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  8. Increased intraepithelial CD3+ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping.

    Science.gov (United States)

    Jesinghaus, Moritz; Steiger, Katja; Slotta-Huspenina, Julia; Drecoll, Enken; Pfarr, Nicole; Meyer, Petra; Konukiewitz, Björn; Bettstetter, Marcus; Wieczorek, Kathrin; Ott, Katja; Feith, Markus; Langer, Rupert; Weichert, Wilko; Specht, Katja; Boxberg, Melanie

    2017-07-18

    Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis and additional therapeutic strategies must be implemented to optimize ESCC treatment. Meanwhile, the important biologic role and potential prognostic and therapeutic implications of a tumors immunologic microenvironment (IM) have been recognized in various cancers.In order to investigate the contexture and the prognostic relevance of the IM in ESCC, we immunohistochemically evaluated the extent of overall/intraepithelial TILs (CD3+/CD8+) and of PD-1 / PD-L1 expression in a cohort of 125 therapy-naive ESCCs, additionally assessing PD-L1 copy number status via fluorescence in-situ hybridization.High intraepithelial CD3+ TILs (CD3ihigh) and high PD-L1 expression on tumor cells (PD-L1high) were each significantly associated with improved overall- (OS) (CD3+: p = 0.019; PD-L1: p = 0.028), disease specific- (DSS) (CD3+: p = 0.05; PD-L1: p = 0.006) and disease free survival (DFS) (CD3+: p = 0.009; PD-L1: p < 0.001). CD3ihigh- and PD-L1high cases were significantly associated with one another (p < 0.001). Subgrouping of ESCC revealed decreased OS (p = 0.031), DSS (p = 0.012) and DFS (p < 0.001) for CD3ilow/PD-L1low cancers.Our data not only associate CD3ihigh- and PD-L1high ESCC with a beneficial outcome, but also demonstrate PD-L1high- and CD3ihigh status to be closely intertwined. Furthermore, our study demarcates a prognostically unfavorable, "non-immunoreactive" CD3ilow / PD-L1low ESCC-subgroup, potentially forming the basis for an immune-based stratification of ESCC.

  9. Risk of persistent and recurrent cervical neoplasia following incidentally detected adenocarcinoma in situ.

    Science.gov (United States)

    Munro, Aime; Codde, Jim; Spilsbury, Katrina; Steel, Nerida; Stewart, Colin J R; Salfinger, Stuart G; Tan, Jason; Mohan, Ganendra R; Leung, Yee; Semmens, James B; O'Leary, Peter; Williams, Vincent; Cohen, Paul A

    2017-03-01

    Adenocarcinoma in situ of the uterine cervix is a precursor to cervical adenocarcinoma and may coexist with both adenocarcinoma and high-grade squamous dysplasia (cervical intraepithelial neoplasia 2 and 3). Up to 60% of adenocarcinoma in situ lesions are detected incidentally following excisional biopsies performed for the treatment of cervical intraepithelial neoplasia 2/3. To date there are no data regarding risk factors for persisting or progressive cervical neoplasia in these patients. We sought to investigate patient outcomes following incidentally detected cervical adenocarcinoma in situ after loop electrosurgical excision procedure or cold knife cone biopsy performed for the treatment of high-grade cervical intraepithelial neoplasia. We conducted a retrospective, population-based cohort study of Western Australian patients with an incidental diagnosis of adenocarcinoma in situ from 2001 through 2012. Primary outcomes were persistent or recurrent cervical intraepithelial neoplasia 2/3 and or adenocarcinoma in situ, and invasive adenocarcinoma during follow-up (neoplasia 2/3, 23 (7.7%) had adenocarcinoma in situ, and 3 (1.0%) had adenocarcinoma diagnosed during the follow-up and surveillance periods. Age >30 years, pure adenocarcinoma in situ lesions, and larger lesions (>8 mm) were associated with a greater risk of disease persistence or recurrence. Following the incidental detection of adenocarcinoma in situ, age >30 years, pure adenocarcinoma in situ lesions, and lesions >8 mm were significantly associated with disease persistence/recurrence. In younger women, incidentally detected adenocarcinoma in situ that coexists with cervical intraepithelial neoplasia 2/3 and is <8 mm extent with clear margins may not require reexcision. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Corpora amylacea and molluscum contagiosum on a cervical pap smear.

    Science.gov (United States)

    Buckley, Kaila; Li, Zaibo

    2017-02-01

    When evaluating a Papanicolaou (Pap) smear, the cytology of the squamous epithelial cells is of utmost importance. This is what cytopathologists use to render a diagnosis, ranging from normal to atypical squamous cells of undetermined significance (ASCUS) to high grade squamous intraepithelial lesions, or even squamous cell carcinoma. However, occasionally the pathologist will run into microscopic noncellular material as in our case, such as corpora amylacea on the slides, or even uncommon viral inclusions such as Molluscum contagiosum (MCV). When these less common entities make their way on to a cervical Pap smear, it is important not only to correctly recognize them, but to understand their clinical implications as well. Diagn. Cytopathol. 2017;45:179-181. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. The Role of Polymerase Chain Reaction of High-Risk Human Papilloma Virus in the Screening of High-Grade Squamous Intraepithelial Lesions in the Anal Mucosa of Human Immunodeficiency Virus-Positive Males Having Sex with Males

    Science.gov (United States)

    Hidalgo-Tenorio, Carmen; Rivero-Rodriguez, Mar; Gil-Anguita, Concepción; Esquivias, Javier; López-Castro, Rodrigo; Ramírez-Taboada, Jessica; de Hierro, Mercedes López; López-Ruiz, Miguel A.; Martínez, R. Javier; Llaño, Juan P.

    2015-01-01

    Objectives To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). Methods This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. Results Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). Conclusions When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL. PMID:25849412

  12. The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

    Directory of Open Access Journals (Sweden)

    Carmen Hidalgo-Tenorio

    Full Text Available To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3 in HIV-positive men having sex with men (MSM.This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation.Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL, and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7% in HSIL screening, with similar positive (PPV and negative predictive value (NPV of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2 or low (<0.4. Area under the receiver operating characteristics (AUROC curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6. Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984, and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827. HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82.When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV suppression with treatment protects against the appearance of HSIL [corrected].

  13. Age and Pattern of Pap Smear Abnormalities: Implications for Cervical Cancer Control in a Developing Country.

    Science.gov (United States)

    Akinfolarin, Adepiti Clement; Olusegun, Ajenifuja Kayode; Omoladun, Okunola; Omoniyi-Esan, G O; Onwundiegu, Uche

    2017-01-01

    To characterize the age and pattern of Pap smear abnormalities in a major teaching hospital in Southwestern Nigeria. This is a review of medical records of patients that came for cervical cancer screening. The Pap smear results of women between May 2013 and April 2015 were retrieved. A total of 2048 Pap smear results were retrieved during the study period and analyzed with Statistical Package for Social Sciences (SPSS) version 20. A total of 252 (12.3%) samples were excluded from the analysis. The mean age of the women was 45.77 ± 9.9 years and the mode was 50 years. Normal Pap smear result was reported in 728 (40.6%) women. Only 20 women has had more than one more than one Pap smear done. The most common abnormality was inflammatory smear result as this was reported in 613 (29.9%) women. Atypical squamous cell of undetermined significance, low-grade squamous intraepithelial lesion (LGSIL), and high-grade squamous intraepithelial lesion (HGSIL) were reported in 117 (5.7%), 209 (10.2%), and 111 (5.4%) women, respectively. Atypical glandular cell and squamous cell carcinoma were reported in 12 (6.0%) and 3 (1.0%), respectively. There is a high incidence of abnormal Pap smear in this environment and women start cervical cancer screening late in their reproductive life, past the age at which cervical premalignant lesions peak. This may be a contributing factor to the high burden of cervical cancer in developing countries.

  14. Optical coherence tomography in vulvar intraepithelial neoplasia

    NARCIS (Netherlands)

    Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.

    2012-01-01

    Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate

  15. Optical Coherence Tomography in vulvar intraepithelial neoplasia

    NARCIS (Netherlands)

    Wessels, R.; Wessels, R.; de Bruin, D.M.; Faber, D.J.; van Boven, H.H.; Vincent, A.D.; van Leeuwen, Ton; van Beurden, M.F.B.; Ruers, Theo J.M.

    2012-01-01

    Abstract. Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to

  16. Polymorphism of Ag(+)-NORs in cervical smears from women with cervical cancer.

    Science.gov (United States)

    Cortés-Gutiérrez, E I; Leal-Elizondo, E; Cerda-Flores, R M; Leal-Garza, C H

    2001-02-01

    To evaluate Ag(+)-stained (Ag(+)-NOR) polymorphism in four groups of patients with various grades of cervical lesions and in a control group. Forty-five women were selected, diagnosed and classified on the bases of the Pap smear and colposcopy/biopsy at Hospital de Ginecologia y Obstetricia del Instituto Mexicano del Seguro Social in Monterrey, Mexico. Five categories were considered: (1) inflammatory, (2) low grade squamous intraepithelial lesions (LSILs), (3) high grade squamous intraepithelial lesions (HSILs), (4) invasive cervical cancer, and (5) normal. The cervical smears were stained by the Ag(+)-NOR method. One hundred cells per slide were counted and classified according to the polymorphism of Ag(+)-NOR dots: typical (spherical) and atypical (large, kidney shaped and clustered). The four shapes of Ag(+)-NORs were quantified by percentage and transformed using the arcsine root procedure. Statistical analysis showed a significant decrease in spherical shape according to neoplastic development. The three atypical shapes showed a significant increase in patients with HSIL and invasive carcinoma in respect to LSIL. Principal components analysis grouped the data at five locations in the plane formed by the first two principal components according to the diagnosis. These findings suggest the potential diagnostic and prognostic value of the determination of Ag(+)-NOR polymorphism in cervical cytology studies.

  17. Temporal Patterns of Cervical Cancer Screening Among Danish Women 55 Years and Older Diagnosed With Cervical Cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Hee, Lene; Blaakær, Jan

    2018-01-01

    OBJECTIVE: The aim of the study was to describe the screening history in postmenopausal women diagnosed with cervical cancer during 1990-2013 by age and screening period. MATERIALS AND METHODS: This hospital-based cohort study included women 55 years and older diagnosed with cervical cancer...... at Aarhus University Hospital, Denmark, during 1990-2013. Information on their previous history of cervical cancer screening was obtained from the Danish Pathology Databank. RESULTS: Overall, 47.0% (95% CI = 42.6-51.4) had no record of screening before their cervical cancer diagnosis. This proportion...... and in women aged 55 to 64 years. Of cases with a record of screening within 5 years, 84.6% (95% CI = 14.5-21.2) had a normal cytology result, whereas only 8.8% (95% CI = 2.9-14.7) had high-grade squamous intraepithelial lesion or worse. CONCLUSIONS: Cervical cancer in older women may partly be attributed...

  18. 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

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    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.

  19. Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

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    Garland, Suzanne M; Paavonen, Jorma; Jaisamrarn, Unnop; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Castellsagué, Xavier; Teixeira, Júlio C; Skinner, S Rachel; Hedrick, James; Limson, Genara; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Del Rosario-Raymundo, M Rowena; Catteau, Grégory; Descamps, Dominique; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

    2016-12-15

    We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. © 2016 UICC.

  20. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

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    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.

  1. Associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical diagnosticada pela histopatologia em mulheres infectadas pelo HIV Association between CD4+ T-cell count and intraepithelial cervical neoplasia diagnosed by histopathology in HIV-infected women

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    Juliana Barroso Zimmermmann

    2006-06-01

    Full Text Available OBJETIVO: avaliar a associação entre a contagem de linfócitos T CD4+ e a gravidade da neoplasia intra-epitelial cervical em pacientes HIV positivas. MÉTODOS: estudo transversal no qual foram incluídas 87 pacientes infectadas pelo HIV, confirmado por testes sorológicos prévios. Todas eram portadoras do HPV cervical, diagnosticado por meio da reação em cadeia da polimerase. Foram realizados anamnese, exame físico e colposcopia de todas em pacientes. A biópsia do colo uterino foi realizada quando indicada pelo exame colposcópico. Os resultados histopatológicos foram classificados com neoplasia intra-epitelial de baixo grau (NIC I ou de alto grau (NIC II e II. A associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão foi verificada por meio da comparação de médias utilizando a análise da variância (ANOVA. RESULTADOS: entre as 60 pacientes biopsiadas foram encontrados 24 casos (40,0% com NIC I, oito (13,3% NIC II, três (5% NIC III, 14 (23,3% pacientes somente com cervicite crônica e 11 (18,3% apresentando efeito citopático produzido pelo HPV, mas sem perda da polaridade celular. Isso equivale a 35 mulheres com lesão intra-epitelial de baixo grau (NIC I + HPV (58,3% e 11 (18,3% com lesão intra-epitelial de alto grau (NIC II + NIC III. A associação entre a média da contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial cervical não foi significativa (p=0,901. CONCLUSÕES: não houve associação entre a contagem de linfócitos T CD4+ e a gravidade da lesão intra-epitelial do colo uterino, diagnosticada pelo exame histopatológico.PURPOSE: to evaluate association between CD4+ cell count and cervical intraepithelial lesion severity in HIV-infected women. METHODS: cross-sectional study of 87 HIV-infected patients which were confirmed by previous serologic examinations. All had cervical HPV diagnosed by polymerase chain reaction (PCR. All patients underwent anamnesis, physical examinations and

  2. Argon plasma coagulation treatment of anal high-grade squamous intraepithelial lesions in men who have sex with men living with HIV: results of a 2-year prospective pilot study.

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    de Pokomandy, A; Rouleau, D; Lalonde, R; Beauvais, C; de Castro, C; Coutlée, F

    2018-02-01

    Men who have sex with men (MSM) living with HIV are at high risk for anal high-grade squamous intraepithelial lesions (HSILs) and cancer. The best management of anal HSIL remains unclear. Our objective was to assess whether argon plasma coagulation (APC) could be safe, well tolerated and efficient to treat anal HSILs in MSM living with HIV. A prospective phase II, open-label, pilot study was conducted to evaluate APC to treat anal HSILs in 20 HIV-positive MSM. Participants were followed for 2 years after their first treatment. Twenty men with persistent HSILs completed the 2-year study. Their baseline median CD4 count was 490 cells/μL and 85% had undetectable HIV viral loads. Overall, 65% (13/20) of participants were clear of HSILs at their 24-month visit. The initial response rates after the first, second and third APC treatments were 45%, 44% and 67%, respectively, but recurrences were common. The main side effect was pain during and within 1 week after the treatments. There were no long-term side effects, nor serious adverse events related to the procedure. Cost is a drawback. APC can be used to treat anal HSILs in HIV-seropositive MSM, and requires repeated treatment because of a high recurrence rate. As successful treatment of human papillomavirus (HPV) infection or eradication of the anal transitional zone remains impossible, HSIL treatment is challenging and requires long-term follow-up. © 2017 British HIV Association.

  3. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

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    Hernández-Montes Jorge

    2012-05-01

    Full Text Available Abstract Background Most infections with human papillomavirus (HPV are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL from low-grade squamous intraepithelial lesions (LSIL patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when

  4. Abnormal cervical cytology risk factors in the Western Black Sea Region and the importance of health insurance.

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    Sımavli, Serap; Kaygusuz, Ikbal; Cukur, Selma; Aksel, Ferda

    2014-01-01

    To evaluate the prevalence of abnormal cervical cytological findings in the Western Black Sea Region and investigate an association between socio-demographic risk factors and the presence of cytological abnormalities. The reports of 11,539 cervical smears diagnosed according to Bethesda System 2001 version in the Pathology Department between January 2011 and December 2012 were reviewed retrospectively from the hospital records and cytopathology reports. Repeated smear results, unsatisfactory smear results, patients with known gynecologic malignancy history, smear results of patients with hysterectomy and smear results of patients whose socio-demographic information could not be obtained were excluded from the evaluation. The results of 7,740 patients who met the criteria for the study were evaluated. The prevalence of cervical cytological abnormalities was 1.8 % in general. The prevalence rates for atypical squamous cells with undetermined significance (ASC-US), atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and atypical glandular cells (AGC) were 1.16%, 0.11%, 0.29%, 0.15%, and 0.03% respectively. The prevalence of cytologically diagnosed cervical invasive neoplasia was 0.025%. Advanced age, low education level (primary school or less) and not having health insurance were found as to be risk factors for preinvasive and invasive lesions. Women who had a high school education and previously had a smear test had decreased risk for developing preinvasive and invasive lesions. This study shows prevalence of abnormal cervical cytology findings and associated risk factors in the Western Black Sea Region of Turkey. The most important risk factor was identified as not having health insurance.

  5. Cytologic features of stratified mucin producing intraepithelial lesion of the cervix--a case report.

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    Goyal, Abha; Yang, Bin

    2014-09-01

    Stratified mucin-producing intraepithelial lesion (SMILE) of the cervix is a human papilloma virus (HPV) associated high grade intraepithelial columnar cell neoplasm that is thought to arise from the reserve cells of the transformation zone. It is composed of immature stratified cells that display intracytoplasmic mucin and is commonly associated with high grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), and invasive carcinoma. Here, we describe the cytologic features of SMILE and discuss its pitfalls in cervical cytology. A 51-year-old woman was diagnosed with SMILE on a cervical biopsy. Histologically, the dysplastic epithelium showed enlarged nuclei with increased nuclear density and presence of mucin-producing columnar cells throughout its thickness. The slides from the last two Pap tests (ThinPrep) performed on the patient were reviewed and compared with the histology. Cytologically, groups of atypical endocervical glandular cells were seen on both Pap tests. These groups showed mild nuclear crowding, slightly enlarged nuclei, nuclear hyperchromasia, and indistinct nucleoli. The borders of these cell groups were relatively smooth. Original cytologic diagnosis was atypical squamous cells of undetermined significance (ASC-US) in both instances. HPV (Hybrid Capture 2) testing was positive on both occasions. Similar to the histology, cytologic features of SMILE are subtle. The features are not typical for AIS or for HSIL and could easily be misinterpreted as reactive. This report emphasizes that careful review of crowded groups of glandular cells in HPV positive women is absolutely critical. Based on our knowledge, this is the first description of the cytologic features of these lesions. Copyright © 2013 Wiley Periodicals, Inc.

  6. The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma

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    Yu Liu

    2015-01-01

    Full Text Available Background: Pelvic lymph node metastasis (LNM is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75-80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs, unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence. Methods: We performed a retrospective review of 296 patients diagnosed with Stage IA-IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People′s Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI, depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy. Results: The incidence of pelvic LNM was 20.27% (60/296 cases. Pelvic LNM (P = 0.00 was significantly correlated with recurrence. Pelvic LNM (P = 0.00, the number of positive pelvic LNs (P = 0.04 and a single group versus multiple groups of pelvic LNM (P = 0.03 had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00, depth of cervical stromal invasion (P = 0.00 and parametrial invasion (P = 0.03 were independently associated with pelvic LNM. Conclusions: Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI

  7. The favourable effects of long-term selenium supplementation on regression of cervical tissues and metabolic profiles of patients with cervical intraepithelial neoplasia: a randomised, double-blind, placebo-controlled trial.

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    Karamali, Maryam; Nourgostar, Sepideh; Zamani, Ashraf; Vahedpoor, Zahra; Asemi, Zatollah

    2015-12-28

    This study was conducted to assess the effects of long-term Se administration on the regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This randomised, double-blind, placebo-controlled trial was carried out among fifty-eight women diagnosed with CIN1. To diagnose CIN1, we used specific diagnostic procedures of biopsy, pathological diagnosis and colposcopy. Patients were randomly assigned to two groups to receive 200 μg Se supplements as Se yeast (n 28) or placebo (n 28) daily for 6 months. After 6 months of taking Se supplements, a greater percentage of women in the Se group had regressed CIN1 (88·0 v. 56·0 %; P=0·01) compared with those in the placebo group. Long-term Se supplementation, compared with the placebo, resulted in significant decreases in fasting plasma glucose levels (-0·37 (sd 0·32) v. +0·07 (sd 0·63) mmol/l; P=0·002), serum insulin levels (-28·8 (sd 31·2) v. +13·2 (sd 40·2) pmol/l; Pplacebo group, there were significant rises in plasma total antioxidant capacity (+186·1 (sd 274·6) v. +42·8 (sd 180·4) mmol/l; P=0·02) and GSH levels (+65·0 (sd 359·8) v. -294·2 (sd 581·8) μmol/l; P=0·007) and a significant decrease in malondialdehyde levels (-1·5 (sd 2·1) v. +0·1 (sd 1·4) μmol/l; P=0·001) among those who took Se supplements. Overall, taking Se supplements among patients with CIN1 led to its regression and had beneficial effects on their metabolic profiles.

  8. Managing atypical squamous cells of undetermined significance (ASCUS): human papillomavirus testing, ASCUS subtyping,or follow-up cytology?

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    Hughes, Sara A; Sun, Deqin; Gibson, Cheryl; Bellerose, Bronya; Rushing, Lynda; Chen, Hao; Harlow, Bernard L; Genest, David R; Sheets, Ellen E; Crum, Christopher P

    2002-03-01

    This study related morphologic subtype, human papillomavirus status, and a second cytologic examination to the follow-up biopsy-proven high-grade squamous intraepithelial lesion (HSIL; grade II or III cervical intraepithelial neoplasia) after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). Seven hundred four liquid-based cervical cytology specimens were classified as normal, "ASCUS, favor reactive" (AFR), "ASCUS, not otherwise specified," "ASCUS, favor low-grade squamous intraepithelial lesion," "ASCUS, favor HSIL" (AFHS), low-grade squamous intraepithelial lesion, and HSIL. Human papillomavirus typing used polymerase chain reaction-restriction fragment length polymorphism analysis. A longitudinal review of the cytologic and histologic records of ASCUS cases with > or =1 follow-up test or biopsy ascertained the frequency of a follow-up diagnosis of biopsy-proven HSIL (grade II or III cervical intraepithelial neoplasia). Three hundred eighty-six cases (208 ASCUS, 68 normal, 86 with low-grade squamous intraepithelial lesions, and 24 with HSIL) were evaluated. High-risk human papillomavirus (HRHPV positive) was lowest with normal cytology (13%), highest with HSIL (71%), and was present in 29.8% of ASCUS cases, ranging from 22.2% (AFR) to 75% (AFHS). Most ASCUS tests (64%) were followed by a negative cytologic or histologic examination. Overall, 3.8% and 11% of ASCUS and HRHPV-positive ASCUS had histologic outcomes of HSIL. AFHS had the highest (25%) and AFR had the lowest (1.1%) proportion of HSIL outcomes. Sensitivity, specificity, and positive predictive values of human papillomavirus testing for biopsy-proven HSIL were 87.5%, 72.5%, and 11.3%, respectively. HSIL and AFHS are distinguished by the highest frequency of HRHPV types and higher rates of HSIL outcome. The remaining categories of ASCUS are heterogeneous with respect to human papillomavirus type and HSIL risk, and the value of subclassification of these entities is

  9. Relative changes of MIB1 and PC10 labeling indexes in cell kinetics during radiotherapy for cervical squamous cell carcinoma

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    Oka, Kuniyuki [Dept. of Pathology, Mito Saiseikai General Hospital, Ibaraki (Japan)]|[National Inst. of Radiological Sciences, Chiba (Japan). Unit of Clinical Examinations]|[National Inst. of Radiological Sciences, Chiba (Japan). Div. of Radiation Medicine; Nakano, Takashi [National Inst. of Radiological Sciences, Chiba (Japan). Unit of Clinical Oncology]|[National Inst. of Radiological Sciences, Chiba (Japan). Div. of Radiation Medicine; Hoshi, Tanji [Tokyo Metropolitan Univ. (Japan). Inst. for Urban Studies]|[National Inst. of Radiological Siences, Chiba (Japan). Research Center of Charged Particle Therapy

    1997-12-31

    To assess the changes in cell kinetics during radiotherapy (RT) in terms of the MIB1 and PC10 labeling indexes of cancer cells, a total of 230 biopsy specimens taken from 76 consecutive patients with cervical squamous cell carcinoma treated with RT was investigated. The MIB1 and PC10 indexes represent the growth fraction and proliferative activity, respectively. The MIB1 index ranged from 11 to 67% (mean value: 38%) before RT, from 21 to 86% (50%) at 5.4 Gy, from 15 to 85% (53%) at 9 Gy, and from 0 to 69% (26%) at 27 Gy. The PC10 index ranged from 4 to 46% (23%) before RT, from 5 to 62% (26%) at 5.4 Gy, from 6 to 63% (23%) at 9 Gy, and from 0 to 35% (11%) at 27 Gy. The correlational relationships between the increment of both indexes during RT ({Delta} index) and the index before RT were analyzed on an individual basis. The {Delta} index was calculated by the index at various doses during RT minus the index before RT. Negative linear relationships were observed between the {Delta} MIB1 index at 9 Gy or {Delta} MIB1 index at 27 Gy and the MIB1 before RT, and also between the {Delta} PC10 index at 9 Gy or {Delta} PC10 index at 27 Gy and the PC10 index before RT. The linear regression coefficient values showed more than 0.5 (0.511 to 0.682) with statistical significance. According to these results, it was suggested that the cervical cancers of lower proliferative activity showed greater increases in growth fraction and proliferative activity by irradiation than those of higher proliferative tumors. These findings suggest that reversal patterns of changes in cell kinetics including growth fraction and proliferative activity took place in the early period of RT for cervical squamous cell carcinomas. The study of changes in cell cycle kinetics in human tumors during RT may have potential impact on the further development of RT. (orig.).

  10. Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis

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    Kou Y

    2017-09-01

    Full Text Available Yurong Kou,1,* Tengfei Zhao,2,* Shaohui Huang,2 Jie Liu,3 Weiyi Duan,2 Yunjing Wang,2 Zechen Wang,2 Delong Li,2 Chunliu Ning,2 Changfu Sun2 1Department of Oral Biology, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Centre of Science Experiment, China Medical University, Shenyang, Liaoning, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis.Materials and methods: Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3.Results: Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0–7.0. Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0–10.0. Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels.Conclusion: Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated

  11. Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma

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    Srivastava, Shruti; Singh, Shalini; Fatima, Naseem; Mittal, Balraj

    2017-01-01

    Introduction MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers. Aim The present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility. Materials and Methods The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. Results Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and miRNA 196a2 polymorphisms showed no association with cervical cancer. However, interaction of miRNA polymorphisms with smoking habit showed higher risk of cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no significant modification in the risk of cervical cancer was seen for other polymorphisms. Conclusion The results of the present study demonstrate that, miRNA 499 T/C polymorphism is significantly associated with genetic susceptibility to cervical cancer and may have a role in its pathogenesis. PMID:29207732

  12. Clinical Validation of Anyplex II HPV HR Detection Test for Cervical Cancer Screening in Korea.

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    Jung, Sunkyung; Lee, Byungdoo; Lee, Kap No; Kim, Yonggoo; Oh, Eun-Jee

    2016-03-01

    The Anyplex II HPV HR detection kit (Seegene Inc, Seoul, Korea) is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk (HR) human papillomavirus (HPV) types in a single tube. To evaluate the clinical performance of the HPV HR kit in predicting high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse in cervical cancer screening. We analyzed 1137 cervical samples in Huro Path medium (CelltraZone, Seoul, Korea) from Korean women. The clinical performance of the HPV HR kit was compared with Hybrid Capture 2 (Qiagen, Valencia, California) using the noninferiority score test in a routine cervical cancer screening setting. The intralaboratory and interlaboratory agreements of HPV HR were also evaluated. Overall agreement between the 2 assays was 92.4% (1051 of 1137) with a κ value of 0.787. Clinical sensitivity of HPV HR for high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse was 94.4% (95% confidence interval [CI], 89.2-99.7) and 92.5% (95% CI, 84.3-100.0), respectively. The respective values for Hybrid Capture 2 were 93.1% (95% CI, 87.2-98.9) and 87.5% (95% CI, 77.3-99.7). Clinical sensitivity and specificity of HPV HR were not inferior to those of Hybrid Capture 2 (P = .005 and P = .04, respectively). The HPV HR showed good intralaboratory and interlaboratory reproducibility at 98.0% (κ = 0.953) and 97.4% (κ = 0.940), respectively. The HPV HR demonstrates comparable performance to the Hybrid Capture 2 test and can be useful for HPV-based cervical cancer screening testing.

  13. Significance of survivin immunoreactivity and morphometric analysis of HPV-induced cervical dysplasia

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    Vukomanović-Đurđević Biserka

    2014-01-01

    Full Text Available Genomic integration of high-risk human papilloma virus in the nucleus of cervical epithelial mucosal cells leads to epithelial dysplasia. The aim of this study was to determine the relevance of correlation between epithelial survivin expression and the degree of human papilloma virus (HPV-induced cervical epithelial dysplasia, and to establish the significance of morphometric analysis of the nuclear area in the assessment of the degree of cervical dysplasia. This retrospective study included 99 women with primary, previously untreated lesions, and colposcopic findings indicating dysplasia, in whom a cytological test by Papanicolaou method was interpreted according to the Bethesda criteria as lowgrade squamous intraepithelial lesion (LSIL, high-grade squamous intraepithelial lesion (HSIL, and atypical squamous cells of undetermined significance (ASCUS. We performed human papilloma virus (HPV typing by PCR for evidence of viruse types 16, 18, 31, 33. After biopsy of the cervical mucosa, we performed hematoxylin-eosin (H-E and Periodic Acid Schiff (PAS staining, and immunohistochemical and morphometric analysis of tissue samples. The control group consisted of 12 women without dysplasia and without a verified infection of cervical high-risk HPV. A high statistical correlation between the degree of dysplasia and expression of survivin was found in patients with different types of cervical dysplasia (p = 0.003. We observed a high statistical difference between the area of nuclei at different degrees of cervical dysplasias (p = 0.000. The high-grade cervical dysplasia had a more than 2-fold higher level of ranking in comparison to low-grade dysplasia, and a more than 10-fold higher ranking than the control group without cervical dysplasia.

  14. Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions.

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    Goulart, Ana Paula Szezepaniak; Gonçalves, Manoel Afonso Guimarães; DA-Silva, Vinicius Duval

    2017-01-01

    to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers' expression, as for disease recurrence, was not statistically significant in the period evaluated. estudar a associação entre a graduação histológica das neoplasias intraepiteliais cervicais (NIC I, NIC II e NIC III) e a expressão imuno-histoquímica para p16ink4a, hTert e Ki67, assim como, avaliar a relação destes marcadores com o risco de recorrência após tratamento cirúrgico. estudo de coorte histórica de 94 mulheres portadoras de lesões intraepiteliais NIC I (baixo grau), NIC II e NIC III (altos graus), submetidas à conização ou à excisão eletrocirúrgica da zona de transformação. Todas as

  15. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

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    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.

  16. Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis

    Science.gov (United States)

    Chen, Mei; Zhang, Yuan; Zheng, Peng-Sheng

    2017-01-01

    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. PMID:28489874

  17. 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.

  18. Penile Analogue of Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: The First Described Case. A Diagnostic Pitfall.

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    Michal, Michael; Michal, Michal; Miesbauerova, Marketa; Hercogova, Jana; Skopalikova, Barbora; Kazakov, Dmitry V

    2016-05-01

    The authors report a case where undifferentiated (classic) penile intraepithelial neoplasia was associated with the presence of goblet cells throughout the full epithelial thickness and which later progressed into an invasive carcinoma. The lesion evolved in three consecutive biopsies from only surface epithelium occupying numerous goblet cells in the first to variably sized solid nodules in the dermis composed of atypical squamous and/or basaloid cells intermixed with numerous goblet cells in the third biopsy. Both cellular components expressed CK7 and p16 protein. Human Papillomavirus (HPV) genotyping revealed high risk HPV type 16. To the best of our knowledge, this is the first description of such a lesion occurring on the penis, which can be considered the penile analogue of cervical stratified mucin-producing intraepithelial lesion (SMILE). The correct diagnosis was rendered retrospectively, after recognition of the existence of a vulvar lesion resembling cervical SMILE. The initial biopsy was misinterpreted as extramammary Paget disease, which also constitutes the main pitfall in the differential diagnosis. Another important differential diagnosis is penile/vulvar mucinous metaplasia. The finding of atypical squamous epithelial cells positive for p16 associated with mucinous cells present throughout the full epithelial thickness is a clue to the diagnosis of penile SMILE.

  19. TLR9 gene polymorphism -1486T/C (rs187084) is associated with uterine cervical neoplasm in Mexican female population.

    Science.gov (United States)

    Martínez-Campos, Cecilia; Bahena-Román, Margarita; Torres-Poveda, Kirvis; Burguete-García, Ana I; Madrid-Marina, Vicente

    2017-12-01

    The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample. Genotyping was performed using predesigned 5' endonuc lease assays and the association of the polymorphisms with the diagnosis groups were assessed by performing multinomial regression models. The relative expression of TLR9 in peripheral blood mononuclear cells was evaluated by real-time polymerase chain reaction and the association of the level of TLR9 expression with the diagnosis was evaluated by performing multinomial regression models. The serum concentration of TLR9 was evaluated in a subsample of patients diagnosed with uterine cervical neoplasm by ELISA. The results showed that genotype TT in the -1486 locus of TLR9 was significantly associated with HPV infection (OR = 3.25, 95% CI 1.12-9.46), squamous intraepithelial cervical lesion (OR = 3.76, 95% CI 1.36-10.41), and uterine cervical neoplasm (OR = 5.30, 95% CI 1.81-15.55). Moreover, the highest level of TLR9 expression was significantly associated with a greater risk for developing squamous intraepithelial cervical lesion and uterine cervical neoplasm. The serum TLR9 concentration was higher in patients with uterine cervical cancer than in controls. Our findings indicate that genotype TT in the -1486 locus of the TLR9 gene could comprise a risk genotype for HPV infection, squamous intraepithelial cervical lesion, and uterine cervical neoplasm in Mexican female population. Further studies with larger samples are needed to evaluate if the peripheral expression of TLR9 could be

  20. Cervical lymphnode metastasis in oral squamous cell carcinoma: Correlation of manual palpation, ultrasonographic, and histopathological findings

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    Sathya P Dongade

    2017-01-01

    Full Text Available Introduction: The staging of cervical lymphadenopathy is an important consideration in the management of oral cancer as it determines the patients' prognosis. Ultrasound is used to image the cervical lymph nodes for staging because it is noninvasive and there is no radiation exposure to the patient. Aim: To investigate the applicability and diagnostic relevance of sonography in staging cervical lymphnode metastases. Materials and Methods: Cervical lymphnodes of the patients were subjected to manual palpation and ultrasound evaluation for its size, number, shape, borders, internal echoes, echogenic hilus, and central necrosis. The manual palpation findings and ultrasound features of the lymphnodes were compared with the histological features for malignant and nonmalignant nodes. Results: When short axis of node is more than 10 mm, 86% were metastatic, nodes with irregular borders were metastatic in 84%, in the absence of the echogenic hilus, 93% were metastatic, 81% were metastatic with heterogeneous nodes, and nodes with central necrosis showed 90% metastasis. Conclusion: By using ultrasound no single parameter showed high sensitivity, specificity, and accuracy.

  1. Human Papillomavirus Types 52 and 58 Are Prevalent in Uterine Cervical Squamous Lesions from Japanese Women

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    Kazuhiro Takehara

    2011-01-01

    Full Text Available Objective. To estimate the prevalence and genotypes of high-risk human papillomavirus (HPV focusing HPV 16, 18, 52, and 58 in Japan. Methods. Liquid-base cytology specimens were collected from Japanese women (n=11022, aged 14–98. After classifying cytodiagnosis, specimens were analyzed for HPV DNA by the multiplex polymerase chain reaction method, where 1195 specimens were positive for cervical smear, except adenomatous lesions. Result. HPV genotypes were detected in 9.5% of NILM and 72.2% of ASC-US or more cervical lesions. In positive cervical smears, HPV genotypes were HPV 52 at 26.6%, HPV 16 at 25.2%, HPV 58 at 21.8%, and HPV 18 at 7.1%. Most patients infected with HPV 16 were between 20–29 years old, decreasing with age thereafter. As for HPV 52 and 58, although the detection rate was high in 30- to 39-year-olds, it also was significant in the 50s and 60s age groups. Conclusion. In Japan, as a cause of abnormal cervical cytology, HPV52 and 58 are detected frequently in addition to HPV 16. In older age groups, HPV 52 and 58 detection rates were higher than that observed for HPV 16. After widespread current HPV vaccination, we still must be aware of HPV 52 and 58 infections.

  2. "ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE: A CYTOHISTOLOGIC STUDY"

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    N. Izadi Mood A. Haratian

    2004-09-01

    Full Text Available Although the diagnostic category of atypical squamous cells of undetermined significance (ASCUS has been known since 1988, its use and appropriate clinical follow up and management still remains controversial. This study was carried out to evaluate the diagnostic value of ASCUS, using cytohistologic correlation. A retrospective review of archival materials in our cytology laboratory files was performed for cervicovaginal smears diagnosed as ASCUS from March 1999 to February 2002. In 8551 cervicovaginal smears examined, ASCUS was reported in 236 (2.76% cases, with histologic follow up in 98 (41.2%. During the follow up period of patients with ASCUS, 51 patients (52% had benign/reactive lesions, 43 patients (43.9% were diagnosed as having a squamous intraepithelial lesion (SIL, 2 (2.1% specimen were insufficient and finally two cases (2% proved to be invasive cervical carcinoma on histology. Of cases diagnosed as SIL, 22 (22.4% were interpreted as flat condyloma, 9(9.1% cervical intraepithelial neoplasia (CIN 1, 2 (2.1% CIN 1-2, 3 (3.1% high grade SIL, 6 (6.1%basal cell abnormality of undetermined significance, and 1 (1% had features of CIN 1 in presence of severe inflammation. Patients whose smears fall into the category of ASCUS may exhibit a spectrum of findings, ranging from benign/reactive lesions to frequent SIL and rarely to invasive carcinoma. Therefore, patients with a diagnosis of ASCUS justify careful follow-up and investigation.

  3. Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

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    Kim, S H; Lee, J M; Yun, H G; Park, U S; Hwang, S U; Pyo, J-S; Sohn, J H

    2017-02-01

    The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients. © 2016 John Wiley & Sons Ltd.

  4. Detection of gene amplification in MYCN, C-MYC, MYCL1, ERBB2, EGFR, AKT2, and human papilloma virus in samples from cervical smear normal cytology, intraepithelial cervical neoplasia (CIN I, II, III), and cervical cancer

    OpenAIRE

    Dabeiba Adriana García; Ignacio Briceño; Marcos Castillo; Fabio Ancizar Aristizábal

    2011-01-01

    Introducción: El cáncer cervical es el segundo cáncer más importante en mujeres a nivel mundial y es la segunda causa de muerte por cáncer en mujeres. Se ha demostrado que el proceso de carcinogénesis cervical presenta componentes tanto genéticos como epigenéticos y medio ambientales. En la actualidad, hay gran interés en la búsqueda de marcadores moleculares asociados con la progresión de esta enfermedad, uno de los posibles mecanismos y que además está poco estudiado en cáncer cervical es l...

  5. Folate deficiency and FHIT hypermethylation and HPV 16 infection promote cervical cancerization.

    Science.gov (United States)

    Bai, Li-Xia; Wang, Jin-Tao; Ding, Ling; Jiang, Shi-Wen; Kang, Hui-Jie; Gao, Chen-Fei; Chen, Xiao; Chen, Chen; Zhou, Qin

    2014-01-01

    Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (χ2=36.64, Pcancer progression. This suggests that FHIT may be an effective target for prevention and treatment of cervical cancer.

  6. Transoral robotic surgery for management of cervical unknown primary squamous cell carcinoma: Updates on efficacy, surgical technique and margin status.

    Science.gov (United States)

    Geltzeiler, Mathew; Doerfler, Sean; Turner, Meghan; Albergotti, William Greer; Kubik, Mark; Kim, Seungwon; Ferris, Robert; Duvvuri, Umamaheswar

    2017-03-01

    Management of cervical unknown primary squamous cell carcinoma (CUP) has evolved with the introduction of transoral robotic surgery (TORS). 1. To describe the efficacy of TORS lingual and palatine tonsillectomy in identifying the primary site of malignancy. 2. To explore how the extent of surgery affects diagnostic yield. 3. To report margin status of TORS resections. A retrospective, single-center cohort study utilizing a prospectively collected database of CUP patients in a high-volume tertiary referral center. Patient underwent operative laryngoscopy plus TORS as clinically indicated. Primary end point was successful identification of the primary. The extent of surgery and margin status were also examined. From 2010-2016, 64 patients with CUP were treated. The primary tumor was found in 51 patients (80%). Fourteen patients (22%) were identified with operative laryngoscopy alone. Fifty patients underwent TORS lingual tonsillectomy ± palatine tonsillectomy with 37 primary tumors identified (74%). The primary was located in the lingual tonsil in 32 patients (86%) and palatine tonsil in 5 patients (10%, p<0.001). Negative margins were achieved in 19 patients (51%). The deep margin was the most commonly positive margin (47%, p=0.049). Operative laryngoscopy with TORS is efficacious, localizing the primary in 80% of patients. If a margin was positive, it was most commonly the deep margin. This study provides valuable information that can help standardize surgical technique, further increasing the diagnostic yield and decreasing the negative margin rate of TORS for CUP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Multifocal microinvasive squamous cell carcinoma with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, vagina, and left salpinx diagnosed five years after conization of cervical CIS.

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    Yang, S W; Kim, W Y; Cho, S H; Yoon, S H; Lim, J Y; Leet, S J

    2014-01-01

    Multifocal microinvasive squamous cell carcinoma (SCC) with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, salpinx, and vagina is extremely unusual. The authors present a case of 69-year-old woman with hydrometra who was found to have multifocal microinvasive SCC in the endometrium. The CIS had spread superficially throughout the entire endometrium up to the fundus, completely replacing the epithelium. The uterine cervix, vaginal surface and left salpingeal mucosa were involved. She had previously undergone conization due to cervical CIS five years prior. The pathologic reports showed clear resection margins at that time. The present case suggests that CIS in the endometrium spread back to the cervix and vagina, although the definite origin of the first CIS was not determined.

  8. The clinical application of HPV E6/E7 mRNA testing in triaging women with atypical squamous cells of undetermined significance or low-grade squamous intra-epithelial lesion Pap smear: A meta-analysis

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    Li Yang

    2017-01-01

    Conclusion: A positive HPV E6/E7 mRNA testing result suggested the women with ASCUS, or LSIL Pap smear was in a truly dangerous position, which is an adverse prognostic factor. It suggested that cervical lesions stay in a progressing status and these women should be referred for colposcopy and strengthen follow-up promptly. Whereas, women with a negative HPV E6/E7 mRNA testing result can increase follow-up interval, by comprehensively considering their situation, thus, avoiding unnecessary colposcopy and reducing the rate of colposcopy and biopsy.

  9. Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands

    NARCIS (Netherlands)

    Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Daemen, Toos CAHH; Postma, Maarten J.

    2016-01-01

    In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of

  10. Vaginal intraepithelial neoplasia: a therapeutical dilemma.

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    Frega, Antonio; Sopracordevole, Francesco; Assorgi, Chiara; Lombardi, Danila; DE Sanctis, Vitaliana; Catalano, Angelica; Matteucci, Eleonora; Milazzo, Giusi Natalia; Ricciardi, Enzo; Moscarini, Massimo

    2013-01-01

    Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics.

  11. Cervical acid phosphatase detection: A guide to abnormal cells in cytology smear screening for cervical cancer

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    Deb Prabal

    2008-01-01

    Full Text Available Background: Cervical acid phosphatase-Papanicolaou (CAP-PAP test has recently been described for detection of acid phosphatase enzyme in abnormal squamous cells, and has been proposed as a biomarker-based technology for the screening of cervical cancer. Materials and Methods: Eighty-one consecutive cervical smears were subjected to routine Papanicolaou (Pap staining as well as CAP-PAP, which combined cytochemical staining for acid phosphatase with modified Pap stain. Statistical evaluation of its utility was examined. Results: Of 81 smears, 16 (19.75% showed the presence of mature squamous cells with acid phosphatase by CAP-PAP technique and were considered positive. Of these 16, atypical squamous cells of undetermined significance (ASCUS or above were initially diagnosed in five of the corresponding routine Pap smears. After re-evaluation with CAP-PAP, eight of the routine Pap smears were considered to have ASCUS or above. Of these eight, three were reported as low-grade squamous intraepithelial lesions and five as ASCUS on conventional Pap smears. The remaining 8/16 CAP-PAP-positive cases were negative for atypical squamous cells on the corresponding Pap smears. None of the CAP-PAP-negative smears were positive on routine Pap smear screening. Conclusions: This study highlights the efficacy of CAP-PAP in quality assurance of cervical smear screening. It is also an inexpensive method for segregating smears for subsequent re-screening. In the absence of trained cytologists in peripheral laboratories, this technique can be adopted for identifying smears that would require proper evaluation.

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

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    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.

  13. Functional variant of the P2X7 receptor gene is associated with human papillomavirus-16 positive cervical squamous cell carcinoma

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    Yang, Yuh-Cheng; Chang, Tzu-Yang; Chen, Tze-Chien; Lin, Wen-Shan; Chang, Shih-Chuan; Lee, Yann-Jinn

    2016-01-01

    Human papillomavirus (HPV) infection and the fate of HPV infected cervical epithelial cells are strictly associated with cervical cancer development. P2X7 receptor has been implicated in both the regulation of immune responses and apoptosis of cervical cancer cells. The study aims to investigate if polymorphisms in the P2RX7 gene are associated with the risk of cervical cancer in Taiwanese women. P2RX7 253 T/C, 835 G/A, and 1513 A/C loss-of-function polymorphisms were genotyped in a hospital-based study of 507 women with cervical squamous cell carcinoma (CSCC) and 1619 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. The frequency of 253 C/C genotype was found to increase significantly in patients with HPV-16 positive CSCC compared with controls (odds ratio = 10.2, 95% confidence interval 1.39–87.8, Pc = 0.03). No significant associations were found for other 2 polymorphisms. Analysis of haplotypes also revealed no significant differences among women with CSCC, those with HPV-16 positive CSCC and controls. In conclusion, inheritance of the C/C genotype at position 253 in the P2RX7 gene may contribute to the risk of HPV-16 associated CSCC in Taiwanese women. PMID:27779103

  14. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

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    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  15. Desempenho do exame colpocitológico com revisão por diferentes observadores e da captura híbrida II no diagnóstico da neoplasia intra-epitelial cervical graus 2 e 3 Performance of cervical cytology with review by different observers and hybrid capture II in the diagnosis of cervical intraepithelial neoplasia grades 2 and 3

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    André Luís Ferreira Santos

    2003-08-01

    Full Text Available Para avaliar o desempenho da colpocitologia (CO de encaminhamento e daquela coletada no serviço de referência, com revisão por diferentes técnicas e observadores, e da captura híbrida II (CH II no diagnóstico da neoplasia intra-epitelial cervical (NIC de alto grau, foram incluídas 105 mulheres atendidas entre agosto de 2000 e junho de 2001 por atipias pré-neoplásicas na CO. Todas foram submetidas à coleta de nova CO e CH II para detecção do DNA-HPV. Foi realizada biópsia cervical em 91, sendo o diagnóstico histológico considerado padrão ouro. Foram descritas a sensibilidade, especificidade e razão de verossimilhança positiva (RVP dos métodos propedêuticos com intervalo de confiança de 95% (IC95%. A sensibilidade e especificidade da CO de encaminhamento foi de 57% e 82% para o diagnóstico de NIC 2 e 3, e a RVP de 3,2 (IC95%: 1,5-6,8. A CO do serviço mostrou uma sensibilidade e especificidade 79% e 84%, respectivamente e RVP de 5,0 (IC95%: 2,5-10,0. A sensibilidade (86%, especificidade (80% e RVP (4,3 foram semelhantes com a revisão lenta realizada pelo segundo observador, havendo uma queda significativa da sensibilidade (64% à revisão rápida pelo terceiro observador. A CH II mostrou alta sensibilidade (100%, baixa especificidade (43% e baixa RVP (1,7, IC95%: 1,4-2,2.To evaluate the performance of initial cervical cytology and that collected at the reference service with a review conducted by different observers and techniques, as well as hybrid capture II, in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN, 105 women attended from August 2000 to June 2001 for preneoplastic atypia upon cervical cytology were included. A new cervical cytology and hybrid capture II for DNA-HPV were conducted in all the patients. Cervical biopsies were taken in 91 women. Performance of the investigative procedures was described by estimating the sensitivity, specificity, and positive likelihood ratio (PLR, with a 95

  16. Repeat cytology and human papillomavirus screening strategies in detecting preinvasive cervical lesions.

    Science.gov (United States)

    Li, Kemin; Yin, Rutie

    2015-02-01

    The aim of the present study was to determine the value of human papillomavirus (HPV) testing in screening patients with preinvasive cervical lesions. Seven hundred thirty-four women diagnosed with atypical squamous cells of undetermined significance (ASCUS+) cervical cytology during routine screening had additional cytologic testing and HPV DNA testing within 6 months of their diagnosis, after which all women who tested positive were referred for colposcopy and biopsy. The test findings were then used to determine the screening value of HPV for diagnosing preinvasive cervical lesions. Cytology and HPV testing were compared by conventional cytology. The odds ratio (OR) of sensitivity using ASCUS+ or low-grade squamous intraepithelial neoplasia (LSIL+) as a cutoff for detecting cervical intraepithelial neoplasia (CIN) II+ was, respectively, 0.78 (0.72, 0.85) and 0.82 (0.70, 0.95) (P ASCUS+ or LSIL+ as the cutoff (P ASCUS+, LSIL+, or high-grade squamous intraepithelial neoplasia (HSIL+) as the cutoff (P ASCUS+ or LSIL+ as the cutoff for the detection of CIN II+ was 1.97 (1.68, 2.31) and 1.10 (1.02, 1.18), respectively (P ASCUS+ or LSIL+ was used as the cutoff (P ASCUS+, LSIL+, or HSIL+ was used as the cutoff (P < 0.01). Cytology and HPV testing and cytology for triage improved the specificity of detecting CIN II+, but this did not improve the sensitivity. Additionally, cytology or HPV testing improved the sensitivity of detecting CIN II+ but not the specificity.

  17. [Effect of extracellular signal-regulated kinas 1/2 expression and HPV16 infection and their interaction in progression of cervical cancerization].

    Science.gov (United States)

    Fan, S L; Ding, L; Ren, Z Y; Chen, X; Sun, X S; Li, C C; Liu, C L; Jia, W L; Li, Q L; Wang, J T

    2017-01-10

    Objective: To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis. Methods: A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 57 cases with cervical intraepithelial neoplasm Ⅱ/Ⅲ (CIN Ⅱ/Ⅲ) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014. The information about their demographic characteristics and risk factors associated with cervical cancer was collected with structural questionnaire, and cervical tissue samples were collected from each subject. HPV16 infection was detected by PCR, and phosphorylation of ERK1/2 (p-ERK1/2) protein expression levels were detected by immunohistochemistry. Meanwhile, cervical cancer cell lines Siha (HPV16 positive) and C33A (HPV negative) were treated with ERK inhibitor U0126 in vitro. Cell proliferation was determined by living cell count, cell cycle and apoptosis was detected by flow cytometry. Results: The HPV16 infection rate (trend χ(2)=17.99, Pcancer. And there might be synergistic actions between the two factors in the progression of cervical cancer. The effect of ERK1/2 activation to HPV16 infection cells might be more significant in the process of cervical cancer cell proliferation and apoptosis.

  18. 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

  19. Infecção por Chlamydia em pacientes com e sem lesões intra-epiteliais cervicais Chlamydia infection in patients with and without cervical intra-epithelial lesions

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    Micheline de Lucena Oliveira

    2008-12-01

    and without intraepithelial cervical lesions attended at specialized ambulatory in Recife (2007 and its association with biologic and demographic variables, habits, reproductive, clinical and gynecologic characteristics. METHODS: A cross-sectional study was conducted including 70 women (35 with cytological cervical lesions and 35 with normal smears. Colposcopy and biopsy when necessary were performed and Chlamydia infection was determined by direct immunofluorescence. Analysis variables were age, race, precedence, schooling, marital status, menarche, age at first sexual intercourse, parity, number of sexual partners, vaginal discharge, previous Pap smear, STD episodes, cervical cauterization, contraceptive methods, familial antecedents of cervical cancer, alcohol intake, use of illicit and immunosuppressive drugs, Papanicolaou result and cervical Chlamydia l infection. To determine the strength of association prevalence ratio (PR and its 95% confidence interval were calculated. Multivariate analysis was performed for controlling potentially confounding variables. RESULTS: the frequency of Chlamydia l infection was significantly greater in patients with intraepithelial cervical lesions (80.0% vs. 14.3%; PR = 5.60; 95% CI = 2,44 - 12,82. When the factors associated with Chlamydia l infection were analyzed, the only variable that remained significantly associated after multivariate analysis was previous episode of STD (OR=63,47; 95% CI = 13,93 - 289,09. CONCLUSION: Chlamydia trachomatis infection is associated with intraepithelial cervical lesions and history of STD should be considered for treatment and follow-up of these patients.

  20. Identificação de tipos de papilomavirus e de outros fatores de risco para neoplasia intra-epitelial cervical Identification of papillomavirus types and other risk factors for cervical intraepithelial neoplasia

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    Terezinha Tenório da Silva

    2006-05-01

    infecção por HPV oncogênico, com os tipos 16, 18, 33, 35, 51, 52, 58 e 83. Dentre as portadoras de lesões de alto grau, houve predomínio de HPV-16 ou variante 16. Nas pacientes com colo morfologicamente normal, também foram identificados os tipos oncogênicos 51, 58 e variante 51.PURPOSE: to identify risk factors for cervical intraepithelial neoplasia (CIN and human papillomavirus (HPV types among women with CIN, and to compare with HPV types among patients with normal cervix. METHODS: a total of 228 patients were studied, of whom 132 with CIN (cases and 96 with normal cervix (controls. In the two groups consisting of women selected among outpatients attended in the same hospital, living near the place of the research, mean ages were similar (34.0±8.3 years and there was a predominance of married women. Possible risk factors for CIN were investigated with the application of a questionnaire surveying age, marital status, level of schooling, age at first coitus, number of pregnancies, number of sexual partners, method of used contraception, reference of previously sexually transmitted diseases (STDs and smoking habits, with a comparison between the studied groups. Samples were collected for oncologic colpocytology and HPV search through polymerase chain reaction (PCR, using MY09/MY11 primers; then colposcopic and histopathological examinations were performed. For statistical analysis of the association between risk factors and CIN, odds ratio with 95% confidence interval and chi2 and Fisher tests were used at a significance level of 0.05. The logistic regression method with the significance expressed by the p value with maximum likelihood was also applied. RESULTS: the following variables remained in the logistic regression model: HPV infection of high oncogenic risk (OR=12.32; CI 95%: 3.79-40.08, reference of previous STDs (OR=8.23; CI 95%: 2.82-24.04, early age at first coitus (OR=4.00; CI 95%: 1.70-9.39 and smoking habit (OR=3.94; CI 95%: 1.73-8.98. PCR was

  1. Cervical cytopathological changes among women with vaginal discharge attending teaching hospital.

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    Salih, Magdi M; AlHag, Fatma Tage El Sir; Khalifa, Mohammed Ahmed; El Nabi, Abdulla H

    2017-01-01

    To find cytology changes among women attending obstetrics and gynaecology clinic with complaints of vaginal discharges. This descriptive hospital-based cytological study was conducted at the outpatient clinic of the obstetrics and gynaecology department. Two hundred women with complaints of vaginal discharge were selected. Their detailed histories were documented on a special request form. Pap smears were then obtained and sent for cytological examination to the cytopathology department. All low-grade squamous intraepithelial lesion (LSIL) cases were advised to follow-up with Pap smears in the next 6-12 months. Those with high-grade squamous intraepithelial lesion (HSIL) were further investigated by a cervical biopsy and managed accordingly. The statistical analysis was performed using, the Statistical Package for Social Science (SPSS). Chi-square and cross-tabulation were used in this study. The cytological examination of Pap smears showed no changes (i.e. negative findings) in 88 (44%) cases, while Candida species infection was the most prevalent, which was found in 67 (33.5%) of the cases. Bacterial vaginosis was found in 39 women (19.5%); 6 women (3%) were reported with dyskaryotic changes. Two cases were found to have LSIL and 4 women had HSIL. Infection is common among the illiterate group of women. Women with vaginal discharges should undergo screening tests for evaluation by cervical smear for the early detection of cervical precancer conditions. There is an urgent need to establish a screening program for cervical cancer in Sudan.

  2. High proportion of abnormal pap smear tests and cervical dysplasia in women with cystic fibrosis.

    Science.gov (United States)

    Rousset-Jablonski, Christine; Reynaud, Quitterie; Nove-Josserand, Raphaëlle; Ray-Coquard, Isabelle; Mekki, Yahia; Golfier, François; Durieu, Isabelle

    2017-12-09

    Insufficient gynecological follow-up and cervical screening has been reported in women with cystic fibrosis (CF). Some of these patients will require a pulmonary transplantation, known to be associated with a higher risk of cervical dysplasia. The aim of this study was to explore the results of cervical screening in adult women with CF, and to report the prevalence of abnormal pap smear tests in this population. We retrospectively analyzed medical records of sexually active women with CF who attended a gynecological consultation in Lyon University CF referral center between June 2014 and December 2015. The primary outcome was the result of the pap smear test. Forty-seven women (32 non-transplanted and 15 transplanted) were included in the study. The median age of the patients was 28 (range 18-53). The clinical examination revealed that 20 (42.5%) women presented an abnormality (inflammatory cervix, cervical or vulvovaginal condyloma). An abnormal pap smear was found in 8/32 (25%) non transplanted women and in 5/15 (33.3%) transplanted women, with no significant difference between the two groups (p=0.75): seven atypical squamous cells of undetermined significance (ASC-US), five low grade squamous intraepithelial lesion (LSIL), one atypical glandular cells (AGC). Six (12.8%) (four non transplanted, and two transplanted) women had an histologically proven dysplasia (four Cervical Intraepithelial Neoplasia (CIN)1, one CIN2, and one endocervical adenocarcinoma in situ). Overall, ten (21.3%) women had a Human Papilloma Virus (HPV) related disease (cervical and/or vulvovaginal). A high proportion of transplanted and non-transplanted women with CF had abnormal pap smear tests and cervical dysplasia. A regular gynaecological follow-up, periodic cervical screening, and routine HPV vaccination are strongly recommended in this population. Copyright © 2017. Published by Elsevier B.V.

  3. Anal intraepithelial neoplasia in HIV+ men

    OpenAIRE

    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 therapy (cART).1 The incidence of anal cancer among HIV+ MSM is now much higher than the incidence of cervical cancer in HIV- negative women before standard cytological screening was introduced, a...

  4. The Common Human Papillomavirus Genotypes among Cervical pre-cancerous and cancerous samples in Kermanshah Province (2013

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    Tayebeh Vaezi

    2017-05-01

    Full Text Available Introduction: It is important to have data on human papillomavirus (HPV from different geographical regions of Iran for health policymakers to make decisions on national programs of HPV vaccination. Because no study was found on HPV genotyping in Kermanshah Province, this study appeared necessary. Methods: Fifty-three paraffin-embedded cervical tissue samples were collected. All samples were evaluated by polymerase chain reaction (PCR or nested-polymerase chain reaction assays with specific primers designed for L1 gene. Positive samples were subjected to sequence and phylogenic tree analysis. Results: Thirty-one out of 53 samples (58.5% were found to be HPV positive. Prominent HPV genotype was HPV16 followed by HPV6, 31 and 53. Based on the histology of cervicitis, only HPV16 was found both in cervicitis and adenocarcinoma while HPV6 and 16 were found in cervical intraepithelial neoplasia I, and HPV6 and 53 were found in cervical intraepithelial neoplasia II. HPV16 and 31 were also found in squamous cell carcinoma. Discussion: Findings from this study support a strong correlation of HPV16 as a leading cause of cervical cancer in this region. It appears that HPV vaccines could drastically reduce the incidence of cervical cancer.

  5. Esvaziamento cervical no carcinoma epidermóide da tonsila Neck dissection in squamous cell carcinoma of the tongue

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    Ali Amar

    2005-02-01

    Full Text Available Avaliar o significado prognóstico dos níveis linfáticos acometidos por metástases nos carcinomas epidermóides da região tonsilar. OBJETIVO: Definir o tipo de esvaziamento cervical eletivo mais apropriado. FORMA DE ESTUDO: Série de casos. MATERIAL E MÉTODO: 51 pacientes com tumor de região tonsilar tratados entre 1992 e 2001. A incidência de metástases foi avaliada nos diferentes níveis linfonodais, bem como sua relação com a extensão do tumor primário para os subsítios anatômicos adjacentes. RESULTADOS: Nos pacientes cN0 foram encontradas metástases apenas nos níveis I e II. Entre os pacientes pN+ com metástases no nível I, 6/7 apresentavam extensão da lesão para a cavidade oral. CONCLUSÃO: O esvaziamento supraomohioideo (níveis I, II e III mostrou ser o mais adequado para o tratamento eletivo do pescoço nos tumores da região tonsilar que se estendem para a cavidade oral. Nos casos N0 restritos à orofaringe, o esvaziamento apenas dos níveis II e III mostrou-se a melhor indicação terapêutica.AIM: The purpose of this study was to assess the prognosis of patients with tonsillar squamous cell carcinoma with different stages of lymph node involvement and to determine the best elective neck dissection for those cases. STUDY DESIGN: Case series. MATERIAL AND METHOD: 51 patients with tonsillar tumors were treated between 1992 and 2001. The incidence of different tumor-node-metastasis stages was evaluated according to primary tumor extension. RESULTS: cN0 patients had metastases in stages I and II only. Among pN+ subjects with stage I metastases, 6/7 had primary tumor extending to oral cavity. CONCLUSION: Supraomohyoid neck dissection (stages I, II and III is the elective treatment of choice when tonsillar primary tumor extends to oral cavity. When primary tumors are limited to the oropharynx, selective neck dissection of stages II and III proved to be more adequate.

  6. Automated classification of Pap smear images to detect cervical dysplasia.

    Science.gov (United States)

    Bora, Kangkana; Chowdhury, Manish; Mahanta, Lipi B; Kundu, Malay Kumar; Das, Anup Kumar

    2017-01-01

    The present study proposes an intelligent system for automatic categorization of Pap smear images to detect cervical dysplasia, which has been an open problem ongoing for last five decades. The classification technique is based on shape, texture and color features. It classifies the cervical dysplasia into two-level (normal and abnormal) and three-level (Negative for Intraepithelial Lesion or Malignancy, Low-grade Squamous Intraepithelial Lesion and High-grade Squamous Intraepithelial Lesion) classes reflecting the established Bethesda system of classification used for diagnosis of cancerous or precancerous lesion of cervix. The system is evaluated on two generated databases obtained from two diagnostic centers, one containing 1610 single cervical cells and the other 1320 complete smear level images. The main objective of this database generation is to categorize the images according to the Bethesda system of classification both of which require lots of training and expertise. The system is also trained and tested on the benchmark Herlev University database which is publicly available. In this contribution a new segmentation technique has also been proposed for extracting shape features. Ripplet Type I transform, Histogram first order statistics and Gray Level Co-occurrence Matrix have been used for color and texture features respectively. To improve classification results, ensemble method is used, which integrates the decision of three classifiers. Assessments are performed using 5 fold cross validation. Extended experiments reveal that the proposed system can successfully classify Pap smear images performing significantly better when compared with other existing methods. This type of automated cancer classifier will be of particular help in early detection of cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. The Application of Classification and Regression Trees for the Triage of Women for Referral to Colposcopy and the Estimation of Risk for Cervical Intraepithelial Neoplasia: A Study Based on 1625 Cases with Incomplete Data from Molecular Tests

    Science.gov (United States)

    Karakitsou, Efrossyni; Chrelias, Charalampos; Pappas, Asimakis; Panayiotides, Ioannis; Kyrgiou, Maria; Paraskevaidis, Evangelos

    2015-01-01

    Objective. Nowadays numerous ancillary techniques detecting HPV DNA and mRNA compete with cytology; however no perfect test exists; in this study we evaluated classification and regression trees (CARTs) for the production of triage rules and estimate the risk for cervical intraepithelial neoplasia (CIN) in cases with ASCUS+ in cytology. Study Design. We used 1625 cases. In contrast to other approaches we used missing data to increase the data volume, obtain more accurate results, and simulate real conditions in the everyday practice of gynecologic clinics and laboratories. The proposed CART was based on the cytological result, HPV DNA typing, HPV mRNA detection based on NASBA and flow cytometry, p16 immunocytochemical expression, and finally age and parous status. Results. Algorithms useful for the triage of women were produced; gynecologists could apply these in conjunction with available examination results and conclude to an estimation of the risk for a woman to harbor CIN expressed as a probability. Conclusions. The most important test was the cytological examination; however the CART handled cases with inadequate cytological outcome and increased the diagnostic accuracy by exploiting the results of ancillary techniques even if there were inadequate missing data. The CART performance was better than any other single test involved in this study. PMID:26339651

  8. The Application of Classification and Regression Trees for the Triage of Women for Referral to Colposcopy and the Estimation of Risk for Cervical Intraepithelial Neoplasia: A Study Based on 1625 Cases with Incomplete Data from Molecular Tests

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    Abraham Pouliakis

    2015-01-01

    Full Text Available Objective. Nowadays numerous ancillary techniques detecting HPV DNA and mRNA compete with cytology; however no perfect test exists; in this study we evaluated classification and regression trees (CARTs for the production of triage rules and estimate the risk for cervical intraepithelial neoplasia (CIN in cases with ASCUS+ in cytology. Study Design. We used 1625 cases. In contrast to other approaches we used missing data to increase the data volume, obtain more accurate results, and simulate real conditions in the everyday practice of gynecologic clinics and laboratories. The proposed CART was based on the cytological result, HPV DNA typing, HPV mRNA detection based on NASBA and flow cytometry, p16 immunocytochemical expression, and finally age and parous status. Results. Algorithms useful for the triage of women were produced; gynecologists could apply these in conjunction with available examination results and conclude to an estimation of the risk for a woman to harbor CIN expressed as a probability. Conclusions. The most important test was the cytological examination; however the CART handled cases with inadequate cytological outcome and increased the diagnostic accuracy by exploiting the results of ancillary techniques even if there were inadequate missing data. The CART performance was better than any other single test involved in this study.

  9. Reliability of the CINtecTM p16INK4a immunocytochemical test in screening cervical precancerous lesions

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    Jović Milena

    2008-01-01

    Full Text Available Background/Aim. Overexpression of p16INK4a has been found to be linked with genomic integration of high-risk human papillomavirus (HPV and the developement of precancerous cervical intraepithelial lesions. The aim of this study was to examine is there a higher positive level of correlation between grade of histological dysplasia and p16INK4a level of expression in cervical smear, compared to results of Papanicolaou test. We also examined the correlation between HPV type, p16INK4a expression and Papanicolau test results. Methods. A total of 48 women with precanceorous cervical lesions and HPV cervicitis and 10 healthy women were enrolled in the study. Papanicolaou test, CINtecTM p16INK4a citological immunohistochemical test, polymerase chain reaction (PCR HPV 16, 18, 31, 33 analysis and histopathology of the lesion were performed in all the patients. Results. Comparing the results of Papanicoulaou test and the grade of histological dysplasia, low-grade squamous intraepithelial lesion (LSIL was confirmed in 38%, and high-grade squamous intraepithelial lesion (HSIL in 69.2% of the patients (p > 0.05. Significant positive correlation was found between p16 overexpression and grade of histological dysplasia (p = 0.000. Overexpression p16 was found in 70% of LSIL and 94.4% of HSIL. Positive correlation was found between p16 overexpression and grade of dysplasia in Papanicolaou test (p = 0.011. In 38% of LSIL and 15% of HSIL cases p16 was not expressed. The most frequently found HPV type in PCR analysis was HPV16. Analysing the results of p16 test according to HPV status and Papanicolaou test rather heterogenous results were obtained. Conclusion. In the patients with precancerous cervical lesions a higher level of correlation was found between the grade of histological dysplasia and p16INK4a level of expression in the cervical smear, compared to the results of Papanicolaou test.

  10. Usual vulval intraepithelial neoplasia in HIV-positive women - a case series.

    Science.gov (United States)

    Toby, M; Conway, K; Sethi, G; Lewis, F

    2016-12-01

    Usual or undifferentiated type vulval intraepithelial neoplasia (VIN) is more common in young women and is usually associated with high-risk human papillomavirus infection. It is associated with the development of basaloid or warty squamous cell carcinoma. Studies have shown that HIV-positive women have an increased risk of VIN and invasive vulval carcinoma, but there is a paucity of data about this cohort of women. The objective of this study was to describe the clinical features and treatment responses of HIV-positive women diagnosed with VIN in a specialist vulval dermatology clinic. HIV-positive women diagnosed with VIN from 2007 to 2013 were retrospectively identified. Data were collected on demographics, clinical features, treatments and outcomes. Seven cases were retrospectively identified. The median CD4 cell count at presentation was 500 cells/mm3 (range 59-761). Five had multifocal VIN. Five were treated with imiquimod alone, one had surgical excision and one patient was treated with imiquimod and surgery. Five of the seven had complete resolution of disease. HIV-positive patients with VIN had good responses to treatment with imiquimod. They were likely to be stable on combination antiretroviral therapy at presentation, have multifocal disease and concurrent vaginal, anal or cervical intraepithelial neoplasia. © The Author(s) 2016.

  11. Age and pattern of Pap smear abnormalities: Implications for cervical cancer control in a developing country

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    Adepiti Clement Akinfolarin

    2017-01-01

    Full Text Available Aim: To characterize the age and pattern of Pap smear abnormalities in a major teaching hospital in Southwestern Nigeria. Design: This is a review of medical records of patients that came for cervical cancer screening. Materials and Methods: The Pap smear results of women between May 2013 and April 2015 were retrieved. A total of 2048 Pap smear results were retrieved during the study period and analyzed with Statistical Package for Social Sciences (SPSS version 20. A total of 252 (12.3% samples were excluded from the analysis. Results: The mean age of the women was 45.77 ± 9.9 years and the mode was 50 years. Normal Pap smear result was reported in 728 (40.6% women. Only 20 women has had more than one more than one Pap smear done. The most common abnormality was inflammatory smear result as this was reported in 613 (29.9% women. Atypical squamous cell of undetermined significance, low-grade squamous intraepithelial lesion (LGSIL, and high-grade squamous intraepithelial lesion (HGSIL were reported in 117 (5.7%, 209 (10.2%, and 111 (5.4% women, respectively. Atypical glandular cell and squamous cell carcinoma were reported in 12 (6.0% and 3 (1.0%, respectively. Conclusion: There is a high incidence of abnormal Pap smear in this environment and women start cervical cancer screening late in their reproductive life, past the age at which cervical premalignant lesions peak. This may be a contributing factor to the high burden of cervical cancer in developing countries.

  12. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

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    Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Yusuf, Mehran [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Cash, Elizabeth [Department of Otolaryngology, University of Louisville, Louisville, Kentucky (United States); Silverman, Craig [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States); Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin [Department of Otolaryngology, University of Louisville, Louisville, Kentucky (United States); Perez, Cesar [Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky (United States); Bert, Robert [Department of Diagnostic Radiology, University of Louisville, Louisville, Kentucky (United States); Redman, Rebecca [Division of Medical Oncology, Department of Medicine, University of Louisville, Louisville, Kentucky (United States); Dunlap, Neal [Department of Radiation Oncology, University of Louisville, Louisville, Kentucky (United States)

    2016-10-01

    Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain

  13. [Combining high-risk human papillomavirus DNA test and cytological test to detect early cervical dysplasia].

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    Qian, De-ying; Cen, Jian-min; Wang, Ding; Zeng, Ren-hai; Lin, Ai-hua; Shu, Yan-hong; Hong, Dan-hua; Huang, Zhi-hong

    2006-01-01

    To assess the value of combining high-risk human papillomavirus (HPV) DNA test and cytological test in detection of early cervical dysplasia. During January 2003 to June 2004, a total of 5210 women were screened by combining high-risk HPV DNA test (hybrid capture II, HC-II) and cytological test (liquid-based ThinPrep cytology test), and the abnormal cytological or HPV DNA findings were further biopsied under the colposcope. The age of the patients was between 17 to 80, the average was 34 +/- 9. Final pathological diagnosis was HPV infection in 890 cases, cervical intraepithelial neoplasia (CIN) I in 83 cases, CIN II in 73 cases, CIN III in 80 cases, invasive cervical cancer in 54 cases, endometrial cancer in 5 cases, vaginal intraepithelial neoplasia in 1 case and cervical tuberculosis in 1 case. Based on the criteria of histology and pathology, the sensitivity, specificity, positive-predictive value and negative-predictive value of high-risk HPV DNA test for detecting all cases of CIN II, III were 92.22%, 74.71%, 5.19% and 99.84% respectively. In detecting all cases of CIN II, III by cytological test, for atypical squamous cell of undetermined signification (ASCUS), the sensitivity, specificity, positive-predictive value and negative-predictive value were 90.00%, 80.34%, 11.94% and 99.63% respectively; for low-grade squamous intraepithelial lesion (LSIL), the sensitivity, specificity, positive-predictive value and negative-predictive value were 70.13%, 91.58%, 11.11% and 99.51% respectively; for high-grade squamous intraepithelial lesion (HSIL), the sensitivity, specificity, positive-predictive value and negative-predictive value were 48.05%, 98.46%, 31.90% and 99.21% respectively. By the combination of high-risk HPV DNA test and cytological test, the sensitivity, specificity, positive-predictive value and negative-predictive value for detecting all cases of CIN II, III were 98.70%, 73.08%, 5.21% and 100.00% respectively. The infection rate of HPV in cervical

  14. Knowledge of Patients' Human Papillomavirus Status at the Time of Cytologic Review Significantly Affects the Performance of Cervical Cytology in the ATHENA Study.

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    Wright, Thomas C; Stoler, Mark H; Aslam, Shagufta; Behrens, Catherine M

    2016-09-01

    With human papillomavirus (HPV) testing, patients' HPV status may be known when reviewing cytology specimens. 41,955 women 25 years or older had cytology and HPV screening. Originally, cytology was reviewed blinded to HPV status. We re-reviewed unblinded to HPV status a subset of 428 cytology slides from women with cervical intraepithelial neoplasia grade 2 + (CIN2+) and 1,287 from women without CIN2+. Of the original interpretations of atypical squamous cells of undetermined significance (ASC-US), 33.7% were downgraded to negative after unblinded review, and 8.7% were upgraded to atypical squamous cells, cannot rule out a high-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Of the original interpretations of ASC-US, 66.7% were downgraded on unblinded review in HPV-negative women and 30.2% were upgraded in HPV 16+/HPV 18+ women. Unblinding increases the sensitivity for cervical intraepithelial neoplasia grade 3+ of cotesting from 54.1% to 62.4% (P = .0015) and the sensitivity of HPV primary screening from 72.2% to 77.1% (P = .0029). With cotesting, specificity with unblinding is improved, whereas with HPV primary screening, there would be a small decrease in specificity. Unblinded cytology increases overall sensitivity with either cotesting or HPV primary screening; specificity is either slightly improved or is not affected by unblinding. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Distribution of human papillomavirus genotypes in women with cervical alterations from north Argentina

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    G D Deluca

    2013-01-01

    Full Text Available Background: Cervical cancer remains a major public health problem in northern Argentina, showing the highest mortality rate in the country (approximately 22 cases/100000 women. Objective: The aim of this study was to provide epidemiological data on the prevalence and type distribution of human papillomavirus (HPV in women with pre-neoplastic lesions before the massive introduction of HPV vaccination in the country. Materials and Methods: Exfoliated cervical cells were collected to screen for HPV using the widely known MY09/11 PCR, followed by the restriction fragment-length polymorphism (RFLP technique from a total of 714 women with previously diagnosed atypical squamous cells of undetermined significance (ASCUS, low-grade squamous intraepithelial lesion (LG-SIL and high-grade squamous intraepithelial lesion (HG-SIL. Results: Overall HPV prevalence was 48.2% in ASCUS (24 different HPV types detected, 66.5% in LG-SIL (37 HPV types detected and 82.6% in HG-SIL (16 HPV types detected. HPV-16 was the most prevalent type among all cases. With respect to multiple HPV infections, 9.6% were observed in ASCUS, 14.3% in LG-SIL and 11.4% in HG-SIL. Conclusion: The major strength of our study is the assessment of a large series of women with cytological alterations in this region. The information attained will be useful as a regional baseline for future epidemiological vigilance, in the context of the national HPV vaccination program.

  16. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

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    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

  17. Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia.

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    Vasiljević, Nataša; Carter, Paul D; Reuter, Caroline; Warman, Rhian; Brentnall, Adam R; Carton, James R; Cuzick, Jack; Lorincz, Attila T

    2017-08-15

    Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter-reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (i) p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high-risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was run on mRNA extracted from formalin-fixed paraffin-embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high-resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61-77) for 85% (95%CI 77-91%) sensitivity. The four-point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71-0.82), compared with 0.71 (95%CI 0.64-0.77) for p16-mRNA and 0.67 (95%CI 0.60-0.74) for Digital IHC. Spearman rank-order correlations were: visual to p16-mRNA 0.41, visual to digital 0.49 and p16-mRNA to digital: 0.22. The addition of p16-mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16-mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  18. Risk of persistent or recurrent neoplasia in conservatively treated women with cervical adenocarcinoma in situ with negative histological margins.

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    Munro, Aime; Codde, Jim; Spilsbury, Katrina; Stewart, Colin J R; Steel, Nerida; Leung, Yee; Tan, Jason; Salfinger, Stuart G; Mohan, Ganendra R; Semmens, James B; Cohen, Paul A

    2017-04-01

    Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins. A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as neoplasia in women who had initial conservative management of AIS with negative histopathological margins. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  19. Screening of cervical cancer in Catalonia 2006–2012

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    de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F. Xavier

    2015-01-01

    The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008–2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden. PMID:25987901

  20. Human papillomavirus genotypes in invasive cervical squamous cell carcinoma in Trinidad Genotipos de virus de los papilomas humanos en carcinoma cervicouterino escamocelular invasor en Trinidad

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    Felicia Hosein

    2013-04-01

    Full Text Available OBJECTIVE: To determine the relative contribution of known high-risk human papillomavirus (HPV genotypes to the occurrence of cervical cancers in Trinidad. METHODS: The distribution of HPV genotypes in cases of invasive cervical squamous cell carcinoma in Trinidad was investigated. This study was a follow-up to an investigation of HPV genotypes in 310 nonsymptomatic women in Trinidad. The latter study showed that cervical HPV prevalence and heterogeneity of genotypes were high in the study population; notably, the genotypes targeted by the available HPV prophylactic vaccines were not the most common types. RESULTS: The current study of 85 cases of invasive cervical squamous cell carcinomas demonstrated that the previously observed heterogeneity in HPV genotype distribution is lost in cases of invasive cervical cancer, with the vaccine-targeted HPV types HPV 16 and HPV 18 becoming the most prevalent. CONCLUSIONS: HPV 16 and HPV 18 were the primary HPV genotypes associated with cases of invasive squamous cell carcinoma in the current Trinidad study. This strong association leads us to conclude that the HPV vaccines targeting HPV 16 and HPV 18 may contribute to reducing the cervical cancer burden in Trinidad.OBJETIVO: Determinar la contribución relativa de los diferentes genotipos de virus de los papilomas humanos (VPH conocidos como de alto riesgo para la aparición de cáncer cervicouterino en Trinidad. MÉTODOS: Se investigó la distribución de los genotipos de VPH en casos de carcinoma cervicouterino escamocelular invasor en Trinidad. Este estudio fue la continuación de una investigación de los genotipos de VPH presentes en 310 mujeres asintomáticas en Trinidad. Este último estudio reveló altas prevalencia de VPH en el cuello uterino y heterogeneidad de los genotipos en la población del estudio; cabe destacar que los genotipos a los que se dirigen las vacunas preventivas de la infección por VPH disponibles no fueron los tipos m

  1. Laser conization for the treatment of cervical intraepithelial neoplasia: the experience of the Colposcopy and Laser Surgery Unit, Department of Obstetrics and Gynecology, Conegliano Hospital

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    Fantin, Gian P.; Grasso, Alessandra; Tasinazzo, Raffaella; Bortolozzi, Giorgio

    1998-01-01

    From November 1990 to December 1995 eighty patients were treated with laser conization. They were high grade CIN extending to the endocervical canal and/or with purely ectocervical lesions and patients with low grade endocervical CIN persisting more than one year or cyto- histological discrepancy. Before surgery all the patients had colposcopy, cytology and guided cervical biopsies. Seventy-six out of eighty underwent local anaesthesia and in three cases a general anaesthetic was required although one case was treated without any anaesthesia. Complementary vaporization of the cone bed was performed in every single case. All specimens were judged fully evaluable by the pathologist. The accuracy of the preconization histology as evaluated in 79 patients. Exact agreement or a one degree discrepancy between punch biopsies and cone specimens was found in 96.25%. We did not find any unexpected invasive carcinoma. The apex of the specimen was free of disease in 93.75% of cases. A high grade lesion on the endocervical margin was found in 4 out of 5 cases with an apex involvement. Stenosis of the external cervical os occurred in 7 cases, 3 of which were symptomatic. In our experience laser conization is an effective and safe treatment of CIN with the results comparable to the literature.

  2. 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

    2017-10-19

    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.

  3. Dysplastic Ichthyosis Uteri-like changes of the entire endometrium associated with a squamous cell carcinoma of the uterine cervix

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    Fadare Oluwole

    2006-05-01

    Full Text Available Abstract Ichthyosis uteri is an exceedingly rare condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. Originally described as an endometrial response to iatrogenically-introduced caustic substances, similar changes have since been described in association with a variety of inflammatory conditions of the endometrium. We describe herein a heretofore undescribed example of a moderately differentiated squamous cell carcinoma of the uterine cervix associated with extensive ichthyosis uteri-like changes of the entire adjacent endometrium. Additionally, the squamous epithelium of the latter also showed multifocal changes diagnostic of a low-grade squamous intraepithelial lesion. The potential genesis of this composite of findings is discussed, as is the neoplastic potential of ichthyosis uteri. It is concluded that a squamous cell carcinoma of the cervix extended proximally into the endometrium, and that there was a colonization of a pre-existing ichthyosis uteri by associated human papillomavirus. The possibility of significant cervical pathology should be considered when plaques of squamous epithelium with low grade dysplastic changes are identified in an endometrial biopsy or curettage.

  4. [Interaction between folate deficiency and aberrant expression related to fragile histidine triad gene in the progression of cervical cancerization].

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    Chen, Xiao; Wang, Jintao; Bai, Lixia; Ding, Ling; Wu, Tingting; Bai, Lan; Xu, Juan; Sun, Xuesong

    2015-04-01

    To explore the interaction between folate deficiency and aberrant expression related to fragile histidine triad (FHIT) gene in the progression of cervical cancerization. A total number of 80 patients with histological diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm I (CIN I), 55 cervical intraepithelial neoplasm II/III (CIN II/III) and 64 cervical squamous cell carcinoma (SCC) were included in this study. Levels of serum folate were detected by microbiological assay method and the methylation status of FHIT gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki (HPV16-positive) was treated with different concentrations of folate. Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of FHIT protein expression were measured in each group. All analyses were performed with SPSS (version 17.0) statistical software. Differences among groups were assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the interaction effects were evaluated by additive model. The levels of serum folate (H = 59.08, P cancer and cervix precancerous lesions, and thus play a synergistic action in the progression of cervical cancerization.

  5. Cervicitis

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    ... a sexually transmitted infection, such as chlamydia or gonorrhea. Cervicitis can develop from noninfectious causes, too. Successful ... result from common sexually transmitted infections (STIs), including gonorrhea, chlamydia, trichomoniasis and genital herpes. Allergic reactions. An ...

  6. Cervicitis

    Science.gov (United States)

    ... virus ( genital herpes ) Human papilloma virus ( genital warts ) Trichomoniasis Other things that can cause cervicitis include: A ... the discharge under a microscope (may show candidiasis , trichomoniasis , or bacterial vaginosis) Pap test Tests for gonorrhea ...

  7. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    Science.gov (United States)

    2017-08-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  8. A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3

    Science.gov (United States)

    Greenfield, William W; Stratton, Shawna L; Myrick, Rebecca S; Vaughn, Rita; Donnalley, Lisa M; Coleman, Hannah N; Mercado, Maria; Moerman-Herzog, Andrea M; Spencer, Horace J; Andrews-Collins, Nancy R; Hitt, Wilbur C; Low, Gordon M; Manning, Nirvana A; McKelvey, Samantha S; Smith, Dora; Smith, Michael V; Phillips, Amy M; Quick, C Matthew; Jeffus, Susanne K; Hutchins, Laura F; Nakagawa, Mayumi

    2015-01-01

    PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted. PMID:26451301

  9. Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis.

    Science.gov (United States)

    Ramachandran, Balaji

    2017-04-01

    Repeated parity and usage of oral contraceptives have demonstrated an increased risk of cervical cancer (CC) in HPV-infected women. These lifestyle observations raise the likelihood that oestrogens and HPV infection might act synergistically to affect cancers of the cervix. In vivo studies have indicated the requirement of oestrogens and ERα in the development of atypical squamous metaplasia followed by cervical intraepithelial neoplasia (CIN) I, II and III. CIN II and III are precancerous cervical lesions that can progress over time to CC as an invasive carcinoma. Recently, there has been evidence suggesting that ERα signalling in the tumour epithelium is a preliminary requisite during cancer initiation that is subsequently lost during tumorigenic progression. Conversely, continued expression of stromal ERα gains control over tumour maintenance. This review summarises the current information on the association between oestrogens and HPV infection in contributing to CC and the possibility of SERMs as a therapeutic option. © 2017 Society for Endocrinology.

  10. Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

    Science.gov (United States)

    Frega, A; Manzara, F; Schimberni, M; Guarino, A; Catalano, A; Bianchi, P; Marziani, R; Cozza, G; Milazzo, G N; French, D; Caserta, D

    2016-09-01

    The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

  11. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN).

    Science.gov (United States)

    Srodon, Monica; Stoler, Mark H; Baber, Gwen B; Kurman, Robert J

    2006-12-01

    It has been proposed that low-grade vulvar and vaginal lesions (VIN 1 and VaIN 1) are flat condylomas and should be designated as such. Moreover, their relationship to high-grade lesions (VIN 3 and VaIN 3) is unclear. Accordingly, this study was undertaken to address these issues by comparing the distribution of human papillomavirus (HPV) types in vulvar and vaginal intraepithelial lesions. We identified 33 cases of VIN 1, 34 cases of VIN 3, 17 cases of VaIN 1, and 16 cases of VaIN 3. In addition, 36 cases of low-grade squamous intraepithelial lesion (LSIL) in the cervix and 116 cases of cervical high-grade squamous intraepithelial lesion were used for comparison. Polymerase chain reaction analysis was performed using both the Roche PGMY and DDL SPF 10 systems. In cases where HPV was detected, the majority of low-grade and high-grade lesions contained a single HPV type. However, a minority of cases were found to have multiple HPV types. Of the VIN 1 cases, a low-risk virus was seen in 22 (67%), with HPV 6 or 11 accounting for 14 (42%). A high-risk virus was detected in 14 (42%) of cases of which 2 (6%) contained HPV 16. Of the VIN 3 cases, all had high-risk HPV of which 31 (91%) were found to have HPV 16. Of the VaIN 1 cases, 6 (35%) were found to have low-risk HPV types. HPV 6 or 11 were not found in these cases. High-risk virus was seen in 13 (76%) VaIN 1 cases, with 1 (6%) containing HPV 16. HPV was detected in 15 of 16 (94%) VaIN 3 lesions, all of which had high-risk types. HPV 16 was found in 8 (50%). In contrast, 2 (6%) of cervical LSIL had low-risk HPV (HPV 6 and 11), whereas 34 (94%) of LSIL cases had high-risk HPVs. Of the cervical high-grade squamous intraepithelial lesion cases, 100% had high-risk HPVs of which 87 (75%) were found to have HPV 16. The findings demonstrate that a significant number of low-grade vulvar and vaginal lesions contain high-risk HPV types, supporting their designation as low-grade intraepithelial lesions rather than flat

  12. Assessment of cervical lymph node metastasis for therapeutic decision-making in squamous cell carcinoma of buccal mucosa: a prospective clinical analysis

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    Essig Harald

    2012-11-01

    Full Text Available Abstract Background Cervical metastasis has a tremendous impact on the prognosis in patients with carcinomas of the head and neck and the frequency of such spread is greater than 20% for most squamous cell carcinomas. With emerging evidence, focus is shifting to conservative neck procedures aimed at achieving good shoulder function without compromising oncologic safety. The purpose of this study was to analyze the pattern of nodal metastasis in patients presenting with squamous cell carcinoma of buccal mucosa. Materials and methods This was a prospective clinical analysis of patients who were histologically diagnosed with squamous cell carcinoma of the buccal cavity and clinically N1 and had not received treatment anywhere else. Patients were analyzed for age and sex distribution, tumor staging, location, and metastasis. Results The incidence of metastatic lymph node in T4 (n=44 was the highest, that is, level I was 100% (44/44, level II was 43.18% (19/44, level III was 15.90% (7/44, and level IV was 4.5% (2/44. Level V was free of metastasis. Among T3 (n=10 lesions, incidence of metastasis in level I was 100% (10/10, level II was 20% (2/10, and level III, IV, and V were free of metastasis. Among T2 (n=6 lesions, incidence of lymph node metastasis in level I was 100% (6/6 and all other levels of lymph nodes were found free of metastasis. Conclusion Lymphatic spread from carcinoma of the buccal mucosa is low. Involvement of level IV is seen in only 3% of patients. A more conservative approach to the neck in patients with carcinoma of the buccal mucosa is recommended.

  13. [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.

  14. Abnormal Cervical Cancer Screening Test Results

    Science.gov (United States)

    ... Viewing of the cervix, vulva, or vagina under magnification with an instrument called a colposcope. Conization: A ... the cervix and vagina and examined under a microscope. Squamous Intraepithelial Lesion (SIL): A term used to ...

  15. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    Science.gov (United States)

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    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. PMID:21760701

  16. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    OpenAIRE

    Ana Cristina Macêdo Barcelos; Márcia Antoniazi Michelin; Sheila Jorge Adad; Eddie Fernando Candido Murta

    2011-01-01

    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, A...

  17. Morphological MRI criteria improve the detection of lymph node metastases in head and neck squamous cell carcinoma: multivariate logistic regression analysis of MRI features of cervical lymph nodes

    Energy Technology Data Exchange (ETDEWEB)

    Bondt, R.B.J. de; Bakers, F.; Hofman, P.A.M. [Maastricht University Medical Center, Department of Radiology, Maastricht (Netherlands); Nelemans, P.J. [Maastricht University Medical Center, Department of Epidemiology, Maastricht (Netherlands); Casselman, J.W. [AZ St. Jan Hospital, Department of Radiology, Bruges (Belgium); Peutz-Kootstra, C. [Maastricht University Medical Center, Department of Pathology, Maastricht (Netherlands); Kremer, B. [Maastricht University Medical Center, Department of Otolaryngology/ Head and Neck Surgery, Maastricht (Netherlands); Beets-Tan, R.G.H. [Academic Hospital Maastricht, Department of Radiology, Maastricht (Netherlands)

    2009-03-15

    The aim was to evaluate whether morphological criteria in addition to the size criterion results in better diagnostic performance of MRI for the detection of cervical lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). Two radiologists evaluated 44 consecutive patients in which lymph node characteristics were assessed with histopathological correlation as gold standard. Assessed criteria were the short axial diameter and morphological criteria such as border irregularity and homogeneity of signal intensity on T2-weighted and contrast-enhanced T1-weighted images. Multivariate logistic regression analysis was performed: diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) and areas under the curve (AUCs) of receiver-operating characteristic (ROC) curves were determined. Border irregularity and heterogeneity of signal intensity on T{sub 2}-weighted images showed significantly increased DORs. AUCs increased from 0.67 (95% CI: 0.61-0.73) using size only to 0.81 (95% CI: 0.75-0.87) using all four criteria for observer 1 and from 0.68 (95% CI: 0.62-0.74) to 0.96 (95% CI: 0.94-0.98) for observer 2 (p < 0.001). This study demonstrated that the morphological criteria border irregularity and heterogeneity of signal intensity on T2-weighted images in addition to size significantly improved the detection of cervical lymph nodes metastases. (orig.)

  18. Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

    Science.gov (United States)

    2017-12-11

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

  19. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology

    Directory of Open Access Journals (Sweden)

    María del R González-Losa

    Full Text Available Integration of human papillomavirus (HPV DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57% and HPV58-positive samples (61%. Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%, followed by samples from low-grade squamous intraepithelial lesions (63% and, finally, samples from invasive cervical cancer (35%. Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555 or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024. In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58.

  20. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology.

    Science.gov (United States)

    González-Losa, María Del R; Puerto-Solis, Marylin; Tenorio Ruiz, Juan; Rosado-López, Ariel I; Hau-Aviles, Oscar; Ayora-Talavera, Guadalupe; Cisneros-Cutz, Isidro; Conde-Ferráez, Laura

    2016-12-01

    Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57%) and HPV58-positive samples (61%). Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%), followed by samples from low-grade squamous intraepithelial lesions (63%) and, finally, samples from invasive cervical cancer (35%). Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555) or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024). In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58.

  1. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.

    Science.gov (United States)

    Lehtinen, Matti; Paavonen, Jorma; Wheeler, Cosette M; Jaisamrarn, Unnop; Garland, Suzanne M; Castellsagué, Xavier; Skinner, S Rachel; Apter, Dan; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Kitchener, Henry; Teixeira, Júlio C; Hedrick, James; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; De Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Mindel, Adrian; De Sutter, Philippe; Bosch, F Xavier; David, Marie-Pierre; Descamps, Dominique; Struyf, Frank; Dubin, Gary

    2012-01-01

    Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58

  2. Preditores de não aderência ao seguimento preconizado para mulheres com lesão intraepitelial escamosa de alto grau (HSIL Predictors of non-adherence to the prescribed follow-up in women with high-grade squamous intraepithelial lesion (HSIL

    Directory of Open Access Journals (Sweden)

    Maria Isabel do Nascimento

    2009-06-01

    with non-adherence to the prescribed follow-up in women with high-grade squamous intraepithelial lesions (HSIL, attending a public health care service in the "Baixada Fluminense", Rio de Janeiro, Brazil. This was a retrospective cohort study including women screened through cytology, entering the health care service between 01/01/2002 and 12/31/2005 and submitted to a colposcopy. Data collection ended on 12/31/07. Through the revision of 1496 medical records, 641 eligible women with a histopathological diagnosis of HSIL obtained after excision of the transformation zone were identified. After application of the exclusion criteria, the study population comprised 537 (84% women, classified into two groups: "non-adherent" (29.4%, who abandoned the follow-up procedures and "adherent" (70.6% who remained in follow-up along the required period. Statistical analysis was carried out though qui-square and t-tests and logistic regression. The final model contained the variables smoker (OR 1.72, not having a job outside the house (OR 1.56, having the examination carried out with a videocolposcopy (OR 1.80, age (OR 0.97 and history of three or more gestations (OR 0.49. The study disclosed a vulnerability profile pointing to individual and organizational-level determinants. Strategies to attain better follow-up must be aimed to modifiable life style factors as smoking and to structural characteristics of health care services in the studied area.

  3. HPV status and favourable outcome in vulvar squamous cancer.

    Science.gov (United States)

    Wakeham, Katie; Kavanagh, Kim; Cuschieri, Kate; Millan, David; Pollock, Kevin G; Bell, Sarah; Burton, Kevin; Reed, Nicholas S; Graham, Sheila V

    2017-03-01

    It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently, it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p = 0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p = 0.02). © 2016 UICC.

  4. Correlation of Cervical Pap Smear with Biopsy in the Lesion of Cervix.

    Science.gov (United States)

    Dhakal, R; Makaju, R; Sharma, S; Bhandari, S; Shrestha, S; Bastakoti, R

    Background Cervical cancer can be controlled to a greater extent by screening to improve morbidity and mortality. Pap smear is important screening method, which has proven to be highly effective in reducing the number of cases and the mortality from cervical carcinoma. Any abnormality detected in pap smear has to be confirmed with cervical biopsy, which remains the reference investigation. Objective To find the changes of cervical cytology by pap smear, to classify cervical lesions into malignant and benign groups on cytological and histopathological basis and to correlate the changes observed in cervical cytology with cervical biopsy. Method This is a prospective cross sectional study done in between July 2014 and July 2015 in Dhulikhel Hospital, Kathmandu University Hospital. During the period, all the samples requested for pap smear were studied. The cases who had undergone both pap smear and cervical biopsy were compared. Clinical data were obtained from requisition submitted along with the cytology and tissue specimens received in the department. Result During the study period, total 1922 pap smears were performed and out of them 75 patients were advised to do cervical biopsy. On cytology, out of total 1922 number of cases, 67.90% were normal, 27.90% were inflammatory smears, 3.80% were unsatisfactory (inadequate) and 0.40% were high grade intraepithelial lesions. Highest numbers of patients screened for pap smear ranged from 31 to 40 years. On histopathology, 78.70% had chronic cervicitis, 8% had normal findings, 1.30% had moderate and 6.70% had severe squamous intraepithelial lesions. The frank malignancy was found in 5.30%. The mean age ± SD for carcinoma was 52.75±6.29. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value of pap smear were 77.80%, 100%, 100% and 97% respectively considering cervical biopsy as the gold standard Conclusion This study revealed a good correlation of cervical cytology with cervical biopsy

  5. Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort.

    Science.gov (United States)

    Koskimaa, Hanna-Mari; Paaso, Anna E; Welters, Marij J P; Grénman, Seija E; Syrjänen, Kari J; van der Burg, Sjoerd H; Syrjänen, Stina M

    2014-02-13

    Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet. We used overlapping 30-35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed. HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children. Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection.

  6. Tumor size, depth of invasion, and grading of the invasive tumor front are the main prognostic factors in early squamous cell cervical carcinoma.

    Science.gov (United States)

    Kristensen, G B; Abeler, V M; Risberg, B; Trop, C; Bryne, M

    1999-08-01

    The objective of this study was to evaluate the prognostic significance of clinical and histopathologic factors, including a new grading system focusing on the invasive tumor front. A retrospective analysis of 125 surgically treated patients with squamous cell cervical carcinoma FIGO stage IB was conducted. For each tumor, the degree of keratinization, nuclear polymorphism, pattern of invasion, and degree of lymphoid infiltration at the invasive tumor front were graded and given scores between 1 and 4. Clinical tumor size, depth of invasion, and grading of the invasive front had prognostic significance in multivariate analysis, while lymph vascular space involvement, lymph node status, and grade of differentiation did not. Based on clinical tumor size, depth of invasion, and grading of the invasive tumor front, patients could be separated into three groups: One group with minimal risk of recurrence (5-year disease-free survival (DFS) of 100%) consisting of 24% of the patients, an intermediate group with a fairly low risk of recurrence (5-year DFS of about 92%), and a high risk group with a 5-year DFS of 45%. This latter group contained 26% of the patients with 78% of all relapses occurring in the total group of patients. The invasive tumor front grading was reliably reproducible, with inter- and intraobserver agreement of 79 to 87% and kappa values of 0.47 to 0.66. Clinical tumor size, depth of invasion, and grading of the invasive tumor front were the main predictors of prognosis in patients with stage IB squamous cell cancer of the cervix. Copyright 1999 Academic Press.

  7. 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.

  8. Multiple Adaptive Neuro-Fuzzy Inference System with Automatic Features Extraction Algorithm for Cervical Cancer Recognition

    Directory of Open Access Journals (Sweden)

    Mohammad Subhi Al-batah

    2014-01-01

    Full Text Available To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL and high-grade squamous intraepithelial lesion (HSIL. The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy.

  9. Multiple adaptive neuro-fuzzy inference system with automatic features extraction algorithm for cervical cancer recognition.

    Science.gov (United States)

    Al-batah, Mohammad Subhi; Isa, Nor Ashidi Mat; Klaib, Mohammad Fadel; Al-Betar, Mohammed Azmi

    2014-01-01

    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy.

  10. [Presence of high risk human papilomaviruses (HPV) in the low grade cervical lesion].

    Science.gov (United States)

    Iljazović, Ermina; Mustadenagić-Mujanović, Jasminka; Karasalihović, Zinaida; Cickusić, E; Avdić, S

    2006-01-01

    Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells undetermined significance (ASCUS) are the most frequent verified cellular abnormalities. Their management are still highly controversial mostly caused by uncertainty about their histology and nature of originate. Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show the association of the benign cellular changes, ASCUS and LGSIL with oncogenic types of HPV and to prove the necessity of more intensive screening of this group of patients. Cytology and pathomorphology analyses were performed first. Identification of the presence of human papiloma virus was carried out by the Digene Hybride Capture II test for all patients. Identification of different HPV types for the particular number of patients was carried out by RFLP (Rsetriction Fragments Length of Polymorphism). Out of the 101 patients in the first group 92 (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV, and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first examined period. The combination of smears with the detection of high risk HPV types increases the triage sensitivity especially at patients with mild.

  11. Can an inadequate cervical cytology sample in ThinPrep be converted to a satisfactory sample by processing it with a SurePath preparation?

    Science.gov (United States)

    Sørbye, Sveinung Wergeland; Pedersen, Mette Kristin; Ekeberg, Bente; Williams, Merete E Johansen; Sauer, Torill; Chen, Ying

    2017-01-01

    The Norwegian Cervical Cancer Screening Program recommends screening every 3 years for women between 25 and 69 years of age. There is a large difference in the percentage of unsatisfactory samples between laboratories that use different brands of liquid-based cytology. We wished to examine if inadequate ThinPrep samples could be satisfactory by processing them with the SurePath protocol. A total of 187 inadequate ThinPrep specimens from the Department of Clinical Pathology at University Hospital of North Norway were sent to Akershus University Hospital for conversion to SurePath medium. Ninety-one (48.7%) were processed through the automated "gynecologic" application for cervix cytology samples, and 96 (51.3%) were processed with the "nongynecological" automatic program. Out of 187 samples that had been unsatisfactory by ThinPrep, 93 (49.7%) were satisfactory after being converted to SurePath. The rate of satisfactory cytology was 36.6% and 62.5% for samples run through the "gynecology" program and "nongynecology" program, respectively. Of the 93 samples that became satisfactory after conversion from ThinPrep to SurePath, 80 (86.0%) were screened as normal while 13 samples (14.0%) were given an abnormal diagnosis, which included 5 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 2 atypical glandular cells not otherwise specified, and 1 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion. A total of 2.1% (4/187) of the women got a diagnosis of cervical intraepithelial neoplasia 2 or higher at a later follow-up. Converting cytology samples from ThinPrep to SurePath processing can reduce the number of unsatisfactory samples. The samples should be run through the "nongynecology" program to ensure an adequate number of cells.

  12. Can an inadequate cervical cytology sample in ThinPrep be converted to a satisfactory sample by processing it with a SurePath preparation?

    Directory of Open Access Journals (Sweden)

    Sveinung Wergeland Sorbye

    2017-01-01

    Full Text Available Background: The Norwegian Cervical Cancer Screening Program recommends screening every 3 years for women between 25 and 69 years of age. There is a large difference in the percentage of unsatisfactory samples between laboratories that use different brands of liquid-based cytology. We wished to examine if inadequate ThinPrep samples could be satisfactory by processing them with the SurePath protocol. Materials and Methods: A total of 187 inadequate ThinPrep specimens from the Department of Clinical Pathology at University Hospital of North Norway were sent to Akershus University Hospital for conversion to SurePath medium. Ninety-one (48.7% were processed through the automated “gynecologic” application for cervix cytology samples, and 96 (51.3% were processed with the “nongynecological” automatic program. Results: Out of 187 samples that had been unsatisfactory by ThinPrep, 93 (49.7% were satisfactory after being converted to SurePath. The rate of satisfactory cytology was 36.6% and 62.5% for samples run through the “gynecology” program and “nongynecology” program, respectively. Of the 93 samples that became satisfactory after conversion from ThinPrep to SurePath, 80 (86.0% were screened as normal while 13 samples (14.0% were given an abnormal diagnosis, which included 5 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 2 atypical glandular cells not otherwise specified, and 1 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion. A total of 2.1% (4/187 of the women got a diagnosis of cervical intraepithelial neoplasia 2 or higher at a later follow-up. Conclusions: Converting cytology samples from ThinPrep to SurePath processing can reduce the number of unsatisfactory samples. The samples should be run through the “nongynecology” program to ensure an adequate number of cells.

  13. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    Directory of Open Access Journals (Sweden)

    Takatori E

    2016-09-01

    Full Text Available Eriko Takatori, Tadahiro Shoji, Anna Takada, Takayuki Nagasawa, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Iwate, Japan Objective: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group with patients who underwent RH without NAC (Ope group. Patients and methods: The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS and overall survival (OS between the groups. Results: There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days in the NAC group and 25 days (21–34 days in the Ope group; the patients in the NAC group were discharged earlier (P=0.032. The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91, and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028. Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24, and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101. Conclusion: NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous

  14. Cost-effectiveness of the conventional papanicolaou test with a new adjunct to cytological screening for squamous cell carcinoma of the uterine cervix and its precursors.

    Science.gov (United States)

    Taylor, L A; Sorensen, S V; Ray, N F; Halpern, M T; Harper, D M

    2000-08-01

    To estimate costs and outcomes of conventional annual Papanicolaou (Pap) test screening compared with biennial Pap test plus speculoscopy (PPS) screening for cervical neoplasms. A Markov model compared cost-effectiveness and outcomes of annual Pap tests with biennial PPS. The model includes direct costs of screening, diagnostic testing, and treatment for squamous intraepitheial lesions and invasive cancers; indirect costs (eg, lost productivity because of cervical cancer); and newer management practices, including human papillomavirus DNA testing. Women aged 18 to 64 years. Screening for cervical neoplasms with either annual Pap smear test or biennial PPS. Marginal cost per life-year gained. The probability of women having squamous intraepithelial lesions, cervical cancer, or death from cervical cancer was lower among women undergoing PPS biennially. A total of 12 additional days of life per woman was gained with biennial PPS during the 47-year model period. Total average cumulative direct medical costs per patient were $1419 for biennial PPS compared with $1489 for annual Pap tests. Total costs, including direct medical costs and indirect costs, were $2185 for PPS compared with $3179 for Pap tests alone. Increased savings and patient outcomes were observed in high-risk populations. Our simulations indicate that biennial screening with PPS is expected to provide cost savings for women older than 18 years compared with annual Pap test screening, especially for those in high-risk populations.

  15. The overtreatment risk of see-and-treat strategy in management of abnormal cervical cytology.

    Science.gov (United States)

    Kim, Ji Ye; Lee, Doo Haeng; Kang, Jun Hyeok; Kim, Kye Hyun; Lee, Kyo Won; Kim, Woo Young

    2014-01-01

    To evaluate the feasibility of conization without a prior punch biopsy for patients with abnormal cytology. A retrospective review was performed for 700 patients who underwent conization at a single institution from January 2003 to August 2012. Each of these patients was assigned to one of two groups, either the 'see-and-treat' group or the 'three-step' group, depending on whether the patient had undergone a punch biopsy before conization or not. The final histologic results of two groups were compared. The overtreatment risk was higher in the 'see-and-treat' group in patients with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASCUS/LSIL) cytology (64.7% in the 'see-and-treat' group vs. 36.5% in the 'three-step' group; p = 0.001). There was no significant statistical difference in the rate of cervical dysplasia or invasive carcinoma in patients with high-grade squamous intraepithelial lesion (HSIL) cytology between groups (91.8% in the 'see-and-treat' group vs. 93.5% in the 'three-step' group; p = 0.793). The patients with HSIL on cytology can be managed by a 'see-and-treat' strategy with a low risk of overtreatment. On the other hand, the 'three-step' management is more appropriate in patients with ASCUS/LSIL cytology. © 2014 S. Karger AG, Basel.

  16. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Mendoza-Catalán Miguel A

    2012-03-01

    Full Text Available Abstract Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL, 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766. Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression.

  17. Human papillomavirus infection in HIV-1 infected women in Catalonia (Spain: implications for prevention of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Valeria Stuardo

    Full Text Available BACKGROUND: High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. METHODS: We enrolled 479 HIV-1-infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. RESULTS: Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL was 3.8%. The most common genotypes were 16(23%, 53(20.3%, and 52(16.2%. The factor associated with HR-HPV infection was age 500 cells/mm(3 (OR,8.4; 95%CI,3.7-19.2, HIV-1 viral load >10,000 copies/mL versus <400 copies/mL (OR,2.1; 95%CI,1.0-4.4, and use of oral contraceptives (OR,2.0; 95%CI,1.0-3.9. Sixty percent of HIV-1-infected women had had one Pap smear within the last 2 years. CONCLUSIONS: The high prevalence of HPV infection and cervical lesions in the HIV-1-infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1-infected women.

  18. [Correlation between high risk type human papillomavirus E6/E7 mRNA and cervical cancer].

    Science.gov (United States)

    Wang, X H; Qian, Y M; Miao, L; Le, Y; Du, J

    2016-07-01

    To investigate the correlation between the positive rate of high risk human papillomavirus(HPV)mRNA E6/E7 and cervical cancer, and provide evidence for the prevention and treatment of cervical cancer. A total of 100 cervical cancer cases and 100 healthy controls were selected in our hospital from January 2015 to December 2015. The fluorescence quantitative PCR and pathological examination on HPV E6/E7 mRNA were carried out. The correlation between HPV E6/E7 mRNA and cervical squamous epithelial lesions were analyzed. In case group, the positive rate of HPV E6/E7 mRNA was 76.0%(76/100). In control group, the positive rate was 13.0%(13/100). The positive rate in case group was significantly higher than that in control group, and the difference was statistically significant(χ(2)=24.522, P0.05). The positive rate of HPV E6/E7 mRNA was significantly higher than high-grade squamous intraepithelial lesion(SIL)rate(26.1%), low-grade SIL rate(17.6%)and atypical squamous cell hyperplasia rate(6.7%), the difference was statistically significant(χ(2)=7.615, P= 0.001; χ(2) =9.114, P=0.001; χ(2)=18.241, Pdetection rate of HPV E6/E7 mRNA in cervical cancer patients was high. And with the increased severity of cervical squamous epithelial lesions, the positive rate of HPV E6/E7 mRNA increased.

  19. Report on a cryotherapy service for women with cervical ...

    African Journals Online (AJOL)

    Background: In low-resource settings, cryotherapy can be cost-effective, affordable, and a first-line treatment for cervical intraepithelial neplasia (CIN) of any grade. Objectives: To report the acceptability, safety and effectiveness of cryotherapy for women with cervical intraepithelial neoplasia (CIN) in Western Kenya.

  20. Incidence of Anal Dysplasia in a Population of High-Risk Women: Observations at a Cervical Pathology Unit.

    Science.gov (United States)

    Oliver-Pérez, María de Los Reyes; Bravo Violeta, Victoria; Legorburu Alonso, Beatriz; Betancor Pérez, Diana; Bebia Conesa, Vicente; Jiménez López, Jesús S

    2017-10-01

    This study aimed to evaluate the incidence of anal dysplasia in women at high risk of developing those lesions and to assess the relationships between positive anal cytology and different risk factors. We performed an observational cross-sectional study involving a patient survey and chart review. The study was conducted at the cervical pathology unit at the Hospital Universitario 12 de Octubre, Madrid, Spain, from 2011 to 2015. Patients were 215 women aged 18 to 65 years old with risk factors for anal dysplasia, for whom anal evaluation was indicated. Anal cytology was performed in all patients. High-resolution anoscopy and anal biopsy were used to investigate abnormalities. All patients completed a survey regarding sexual practices. The patients' demographic and clinical data were collected by using a retrospective chart review. The main outcome measure was the incidence of anal dysplasia in this population. Of the 215 patients, 45 (21.0%) presented with cytological abnormalities (atypical squamous cells of undetermined significance, 13.5%; low-grade squamous intraepithelial lesion, 5.6%; high-grade squamous intraepithelial lesion, 1.9%). Anoscopy was performed in 31 patients (14.4%) and 2 patients (0.9%) had abnormal findings. One case (0.5%) of low-grade anal intraepithelial neoplasia was identified. Only immunosuppression (p = .01) and smoking status (p = .02) were significantly correlated with positive anal cytology results. Limitations of the study include the small single-center sample, a lack of controls, the retrospective design, potential survey response biases, and the nonstandardized survey. The incidence of abnormal cytological findings was 21.0%, whereas low-grade anal intraepithelial was confirmed in 0.5% of the patients. There is a higher incidence of cytological abnormalities among immunosuppressed women and smokers.

  1. Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

    Directory of Open Access Journals (Sweden)

    Maha Imam Ahmed

    2004-01-01

    Full Text Available Matrix metalloproteinases (MMPs, a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA, and tissue polypeptide – specific antigen (TPS in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA, we analyzed 50 patients with cervical carcinoma (CC and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR and 95% confidence interval (CI for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between p