Anal squamous intraepithelial lesions in HIV+ MSM

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Siegenbeek van Heukelom, M.L.

2018-01-01

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

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

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

2010-02-01

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 Therefore, cryotherapy should not be withdrawn from such programs.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

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.

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

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

2012-01-01

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

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

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Maria do Socorro Nobre

2016-05-01

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

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

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

2015-08-01

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

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

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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...

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

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

2012-01-01

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

Fractal analysis of cervical intraepithelial neoplasia.

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Markus Fabrizii

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

Prevalence of Cervical Dysplasia among Women in Kano Municipal ...

African Journals Online (AJOL)

Fifty-seven women had cervical dysplasia giving a prevalence rate of 10.63%. Of the 57 women with cervical dysplasia, 21 (36.8%) had a low grade squamous intraepithelial lesions (LGSIL), while 36(63.2%) had a high grade squamous intraepithelial lesion (HGSIL). The disease was higher in grand multiparous clients ...

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

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

2011-06-01

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

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

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

2015-01-01

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

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

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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.

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

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

2017-12-15

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

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

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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...... was poor in Denmark. Our findings suggest that because of this poor adherence, recommendations for long-term annual follow-up after treatment of cervical intraepithelial neoplasia may not be highly effective. Shorter follow-up schedules using highly sensitive tests appear attractive....

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.

HPV-genotypes in high-grade intraepithelial cervical lesions in Danish women

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Kirschner, Benny; Schledermann, Doris; Holl, Katsiaryna

2013-01-01

A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women.......A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women....

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

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

2013-02-18

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

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

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Caroline Alves de Oliveira

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

Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

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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....

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

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

2018-04-01

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

Characteristic findings of cervical Papanicolaou tests from transgender patients on androgen therapy: Challenges in detecting dysplasia.

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Adkins, B D; Barlow, A B; Jack, A; Schultenover, S J; Desouki, M M; Coogan, A C; Weiss, V L

2018-02-28

The characteristic features of Papanicolaou (Pap) tests collected from female-to-male (FTM) transgender patients on androgen therapy have not been well defined in the literature. FTM transgender patients require cervical cancer screening with the same recommended frequency as cis-gender females. Dysplasia remains challenging to differentiate from atrophy. Without pertinent history, the atrophic findings in younger transgender patients can be misinterpreted as high-grade dysplasia. A review of all cervical Pap tests of transgender patients receiving androgen therapy (2010-2017) was performed. Bethesda diagnosis, cytomorphological features, HPV testing and cervical biopsy results were reviewed. Eleven transgender patients receiving androgen therapy were identified with 23 cervical Pap tests, 11 HPV tests and five cervical biopsies performed. A review of the Pap tests demonstrated: 57% negative for intraepithelial lesion; 13% unsatisfactory; 13% atypical squamous cells of undetermined significance; 13% atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion; and 4% high-grade squamous intraepithelial lesion. The rates of abnormal tests were higher than our age-matched cis-gender atrophic cohort rates of unsatisfactory (0.5%), atypical squamous cells of undetermined significance (7%), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (0%) and high-grade squamous intraepithelial lesion (0.5%). The cytological findings from liquid-based preparations included dispersed and clustered parabasal-type cells, scattered degenerated cells, smooth evenly dispersed chromatin, and occasional mild nuclear enlargement and irregularity. Dysplastic cells had larger nuclei, hyperchromatic clumped chromatin, and more irregular nuclear contours. The evaluation of dysplasia can be challenging on Pap tests from transgender patients on androgen therapy. The cohort evaluated had higher rates of unsatisfactory and abnormal Pap tests

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

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

2017-10-01

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

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

Science.gov (United States)

Stewart, Colin J R

2017-08-01

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

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.

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....

EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

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Kodali Venkataramana

2017-03-01

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

Cervical screening with Luviva machine for early detection of ...

African Journals Online (AJOL)

Cervical screening with Luviva machine for early detection of cervical dysplasia: ... glandular cell (AGC), Atypical glandular cell favouring neoplasia (AGC-FN), ... in low grade squamous intraepithelial lesion was recorded among the patients.

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

NARCIS (Netherlands)

Koeneman, M. M.; Kruse, Arnold-Jan; Kooreman, L. F. S.; zur Hausen, Axel; Hopman, Anton H N; Sep, S. J. S.; Van Gorp, T.; Slangen, B. F. M.; van Beekhuizen, H. J.; de Sande, Michiel A. J. van; Gerestein, Cornelis G.; Nijman, H. W.; Kruitwagen, R. F. M. P.

2017-01-01

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

EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

OpenAIRE

Kodali Venkataramana; Prasad Usha

2017-01-01

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

Risk Factors for Cervical Intraepithelial Neoplasia

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Estrella de la Caridad Armenteros Espino

2016-09-01

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

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.

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

Science.gov (United States)

2000-03-01

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

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

DEFF Research Database (Denmark)

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

2006-01-01

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

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

Science.gov (United States)

Wang, Zhen-Ming

2014-01-01

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

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

DEFF Research Database (Denmark)

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

2008-01-01

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

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%.

Human papillomavirus infection among Bangladeshi women with cervical intraepithelial neoplasia and chronic cervicitis

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Elisha Khandker

2016-01-01

Full Text Available Background and objectives: Cervical cancer is one of the leading causes of morbidity and mortality. Human papillomavirus (HPV is known to be associated with cervical intraepithelial neoplasia (CIN and cancer. The objective of the present study was to determine the rate of HPV infection among the Bangladeshi women with different grades of CIN and cancer. Methods: Women aged 20 to 55 years, diagnosed as a case of chronic cervicits, cervical intraepithelial neoplasia (CIN or invasive cancer by Papanicolaou (Pap smear and colposcopy directed biopsy were enrolled in the study. High and intermediate risk oncogenic HPV were detected in cervical samples by real time PCR (rt-PCR. Results: Seventy two women with chronic cervicitis and different grades of CIN were included in the study. Out of 72 cases, 28 (38.9% and 44 (61.1% had chronic cervicitis and CIN respectively. Overall, the HPV infection rate was 43.1% (95% CI= 32%-54% among the study population. CIN cases had significantly high (p<0.01 HPV infection (78.6%; 95% CI=60%-89% compared to cases with chronic cervicitis (18.2%; 95% CI=11.1%-34.5%. Women between the age of 20-30 years had the highest positive rate (50.0% followed by 31-40 years age group (43.6%. All CIN grade 2 and 3 had HPV infection. Conclusion: The study showed that HPV was strongly associated with different grades of CIN. Specific HPV types should be determined to find out the most prevalent HPV types among the Bangladeshi women with CIN and cervical cancers. IMC J Med Sci 2016; 10(1: 29-32

ATYPICAL MITOTIC FIGURES AND THE MITOTIC INDEX IN CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

VANLEEUWEN, AM; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

1995-01-01

We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation

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.

3-GROUP METAPHASE AS A MORPHOLOGIC CRITERION OF PROGRESSIVE CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

MOURITS, MJE; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

Three-group metaphase as a morphologic criterion of progressive cervical intraepithelial neoplasia

NARCIS (Netherlands)

Mourits, M. J.; Pieters, W. J.; Hollema, H.; Burger, M. P.

1992-01-01

OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

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

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Omar Clavero

2017-06-01

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

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.

Cold-knife and laser conization for cervical intraepithelial neoplasia

DEFF Research Database (Denmark)

Tabor, A; Berget, A

1990-01-01

In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice...

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.

ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

Science.gov (United States)

Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

2009-06-01

To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

International Nuclear Information System (INIS)

Kato, H.; Torigoe, T.

1977-01-01

A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

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

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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

Environmental exposure to cooking oil fumes and cervical intraepithelial neoplasm

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Wu, M.-T.; Lee, L.-H.; Ho, C.-K.; Wu, S.-C.; Lin, L.-Y.; Cheng, B.-H.; Liu, C.-L.; Yang, C.-Y.; Tsai, H.-T.; Wu, T.-N.

2004-01-01

The fumes from cooking oil, similar to cigarette smoke, contain numerous carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, nitro-polycyclic aromatic hydrocarbons, etc. In this study, we examined the association between exposure to cooking oil fumes and the risk of cervical intraepithelial neoplasm. The study population in this nested case-control study consisted of women above the age of 19 years living in Chia-Yi County, located in the southwestern Taiwan, who had received pap smear screening between October, 1999, and December, 2000 (n=32,466). The potential cases were women having lesions greater than cervical intraepithelium neoplasm II (≥CIN2) reconfirmed by cervical biopsy (n=116). The potential controls (case: control=1:2) were age-matched (±2 years) and residence-matched women who had normal pap smears within 6 months of the cases. In total, 100 cases and 197 controls were completely interviewed by public health nurses about cooking methods, ventilation, and other potential risk factors. Women who cooked at home in a kitchen (n=269) without the presence of a fume extractor at least once a week between the ages of 20 and 40 had a 2.29 times higher risk [95% confidence interval (CI)=1.08-4.87] of developing cervical intraepithelial neoplasm than those who did not cook once a week in such a kitchen during the same age span, after adjusting for other potential confounders. This finding was further strengthened by the finding that women who did not use the fume extractors had a 2.47 times higher risk (95% CI=1.15-5.32) of developing cervical intraepithelial neoplasm than women who cooked in kitchens with fume extractors that were always switched on while cooking. We also found a joint protective effect of fume extractor use among women older than 40 years (n=202) if they used the extractors during both age spans of their lives, ages 20-40 and >40 years. Comparing our findings on women more than 40 years old who used fume extractors during

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

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

2018-06-01

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

Cervical cytological abnormalities and human papilloma virus infection in women infected with HIV in Southern India.

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Thunga, Suchitra; Andrews, Anusmitha; Ramapuram, John; Satyamoorthy, Kapaettu; Kini, Hema; Unnikrishnan, B; Adhikari, Prabha; Singh, Prakhar; Kabekkodu, Shama Prasada; Bhat, Samatha; Kadam, Anagha; Shetty, Avinash K

2016-12-01

The aim of this study was to examine the association between CD4 count, human papilloma virus (HPV) infection, and the risk of cervical intraepithelial neoplasia among HIV-infected women. A cross-sectional study was conducted among 104 HIV-infected women attending an antiretroviral therapy clinic. They underwent Pap smear and cervical HPV DNA testing. The overall prevalence of HPV infection was 57.7%. HPV 16 was the commonest genotype found (38.5%); HPV 16 and 18 put together contributed to 73.3% of HPV infection; 27.5% of HIV-infected women had squamous cell abnormalities. Cervical intraepithelial neoplasia was less likely among women with CD4 count > 500/mm 3 (12%) and in those without opportunistic infections (17.8%). The prevalence of high-risk HPV infection was higher in women with high-grade squamous intraepithelial lesions or greater lesions (85.7%) as compared to women with normal cytology (52.1%). The high prevalence of HPV infection and cervical intraepithelial neoplasia in HIV-infected women warrants the need for regular Pap smear screening in these women and routine HPV vaccination for adolescents to reduce the burden of cervical cancer in India. © 2016 Japan Society of Obstetrics and Gynecology.

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

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

2016-01-01

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

Computational model for squamous cells characterization during cervical smear cytology

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Víctor Eduardo Martínez Abaunza

2005-07-01

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

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

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Xulian Lu

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

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

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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

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

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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.

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

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Newton Sérgio de Carvalho

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

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.

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

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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.

Treatment of cervical intraepithelial neoplasia in Denmark 1991 to 2007

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Barken, Sidsel Svennekjær

2010-01-01

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

Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

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Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

2008-05-01

To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

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

2006-01-01

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

Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia

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

2015-01-01

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

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

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

2014-04-01

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

Prevalence of anal cytological abnormalities in women with positive cervical cytology.

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Calore, Edenilson E; Giaccio, Claudia Maria Serafim; Nadal, Sidney R

2011-05-01

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty-nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high-grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re-infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323-327. © 2010 Wiley-Liss, Inc. Copyright © 2010 Wiley-Liss, Inc.

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

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Naomi Jay

2015-12-01

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

Frequency of cervical intraepithelial neoplasia treatment in a well-screened population

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Barken, Sidsel Svennekjaer; Rebolj, Matejka; Andersen, Erik Søgaard

2012-01-01

Treatment of cervical intraepithelial neoplasia (CIN) detectable at screening has helped reduce the incidence of cervical cancer, but has also led to overtreatment. The estimates of overtreatment have often focused on a particular grade of CIN or age group. The aim of this paper was to provide...... a nationwide population-based estimate of the frequency of CIN treatment per prevented cervical cancer case in a well-screened population. We retrieved the data from the Danish National Population, Patient, Health Insurance, Pathology, and Cancer Registers, and calculated annual age-standardized CIN treatment...... rates. We estimated the frequency of CIN treatment per prevented cervical cancer case by comparing the cumulative life-time risk of CIN treatment from 1996 onward, with the difference in the cumulative life-time risks of cervical cancer in the prescreening and the screening periods. Since 1996, more...

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

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Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

2018-01-01

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

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.

Cervical screening programme in Trabzon county

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Şafak Ersöz

2010-03-01

Full Text Available AIM: Cytological evaluation carries a great significance for the early detection and treatment of invasive cervical carcinoma precursors. Pap-smear test are considered as a quite effective screening method for this purpose. This screening can be easily performed at the first step health care centers without causing an economic burden if only selected patients were referred to second and third step medical care centers. In this program we aimed to perform a cross-sectional survey for cervix cancer in Trabzon center and surrounding area using cervical smears obtained at first step health care centers. MATERIAL-METHOD: A total number of 3000 cases with an age range of 25-64 were screened between March and May of 2007. This program was supported by USIDER. Smears obtained with cytological brushes were prepared with conventional methods and stained with Papanicolaou dye. Pap smears were reviewed by two pathologists according to 2001 Bethesda classification. RESULTS: A great majority of the smears (93.3 % were found to be satisfactory, while only 6.7 were found to be insufficient. Analysis of satisfactory cervical smears revealed cervical epithelial cell anomalies in 73 cases (2.4%; of these cases 57 (1.9% had atypical squamous cell of undetermined significance (ASC-US, 11 (0.4 % had low grade squamous intra-epithelial lesion (LSIL, 3 (0.1% high grade squamous intra-epithelial lesion (HSIL, and 2 (0.07 % had squamous cell carcinoma. CONCLUSION: Smears obtained at the first step health care centers were found to be satisfactory in a major proportion of the cases. Screening programs play a great role in the declining of cancer incidence. These screening programs should be included in national health politics. First step health care centers might be used for this purpose concerning the health economics.

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance

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Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

2015-01-01

Objective Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. Methods A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of ...

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

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.

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

2012-01-26

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

Increased burden of treatment of cervical intraepithelial neoplasia: Denmark 1991 to 2007

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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...

A comparative study of cervical smears in an urban Hospital in India and a population-based screening program in Mauritius

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Mulay Kaustubh

2009-01-01

Full Text Available Objective: To study cervical smear abnormalities in urban women in India and women in Mauritius and to compare the results in the two groups. Study Design: An analysis of 6010 cervical smears taken as part of routine check-ups in an urban hospital was done and an analysis of 10,000 cervical smears taken from women participating in a National Cancer Screening Program in Mauritius was done. Emphasis was put on cervical epithelial cell abnormalities and the results in the two populations are compared with that of similar studies in other parts of the world. Results: Non specific inflammation formed 19.6% and 25.34% of the smears in the Indian and Mauritian groups, respectively (with specific infection forming 6.05% and 15.08%. The epithelial abnormalities constituted 1.392% of the Indian group and 0.47% of the Mauritian group. The difference was statistically significant in the atypical squamous cells of uncertain significance (ASCUS and atypical glandular cells of uncertain significance (AGUS group. Conclusions: The prevalence of low-grade squamous intraepithelial lesions (LSIL and high-grade squamous intraepithelial lesions (HSIL is similar to that in the developed world.

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

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Darin Ruanpeng

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

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

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

2016-01-01

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

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

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

1991-01-01

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

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

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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

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

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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)....

A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science.

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Allameh, Tajossadat; Moghim, Sharareh; Asadi-Zeidabadi, Maryam

2011-12-01

Given the importance of epidemiological studies on the prevalence of human papilloma virus (HPV) and its subtypes to plan more effective strategies for cervical cancer prevention, the aim of this study was to determine the prevalence of HPV in women with cervical intraepithelial neoplasia and cancer in Isfahan. In this descriptive cross-sectional study, women referred to oncology clinic of Shahid Beheshti Hospital because of abnormal cytology of their cervices within the last year were studied. The 2001 Bethesda system was used for histologic classification. The distribution of different pathologies was as follows: squamous cell carcinoma (SCC) 34.7%, low-grade squamous intraepithelial lesions (LSIL) 30.5%, high-grade squamous intraepithelial lesions (HSIL) 22.8%, atypical squamous cell of undetermined significance (ASCUS) 8.4%, and adenocarcinoma (AC) 3.3%. There was no case of atypical glandular of undetermined significance or cases of adenocarcinoma associated with an early lesion. The presence of HPV infection and its subtypes including HPV 16, 18, 6 and 11 was assessed in different cytological categories of cervical neoplasia, by using polymerase chain reaction method. During this study, 130 patients were studied. Their median age was 52 years (range 29-73 years). HPV was detected in 118/130 patients (90.8%) with abnormal cervical cytology. The prevalence of positive HPV samples was 97.6, 80, 93.1, 92.3, and 66.6% in cases with SCC, AC, HSIL, LSIL, and ASCUS, respectively (P prevalence of HPV type 16 was not significantly different in various cytological categories of cervical neoplasia (P > 0.05). The prevalence of HPV type 16 and 18 was significantly higher than the HPV type 11 or 6 in cervical neoplastic lesions (P prevalence of HPV infection in all categories of cervical neoplasia. This emphasizes the importance of HPV screening and vaccination programs. In order to assess more effective screening programs in Isfahan and evaluate the cost-effectiveness of

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

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

2017-09-01

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

Prevalence of intraepithelial lesion in cervical screening cytology in a First-level Care Unit

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Solís, José Gabriel; Briones-Torres, Tomás Iván

2018-01-01

Cervical cancer represents the second leading cause of malignant neoplasm mortality in women globally. Cervical cytology is the most important screening study. It is therefore of interest to know the prevalence of cytological alterations in the Mexican population. In this study the objective was to calculate the prevalence of intraepithelial lesion in cervical screening cytology. An observational, descriptive and cross-sectional study was developed; the sample was 379 patients from 21 to 64 years of age; we included patients who underwent cervical screening cytology registered in the Detección Oportuna de Cáncer Cervicouterino (DOC-CACU) program database. A descriptive analysis of the data was performed. A prevalence of intraepithelial lesion of 4.49% was found. The 3.17% corresponded to LIEBG and 1.32% to LIEAG. No reports of invasive carcinoma were found. Of these patients, 64.71% corresponded to the age group from 41 to 60 years. 52.94% had had their last cytology in the previous 3 years or more and 35.29% were in postmenopause. A prevalence consistent with what was described in the literature was found. More than half of the affected patients had their last cytology in the previous 3 or more years and corresponded to the age group from 41 to 60 years. A high proportion of patients were in postmenopause.

Photodynamic therapy of cervical intraepithelial neoplasia

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Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

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Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

2016-02-01

Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

Viral load and genomic integration of HPV 16 in cervical samples from HIV-1-infected and uninfected women in Burkina Faso.

Science.gov (United States)

Rousseau, Marie-Noelle Didelot; Costes, Valérie; Konate, Issouf; Nagot, Nicolas; Foulongne, Vincent; Ouedraogo, Abdoulaye; Van de Perre, Philippe; Mayaud, Philippe; Segondy, Michel

2007-06-01

The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV 16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and cervical cytology were studied among women enrolled in a cohort of female sex workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV 16 viral load in cervical samples was determined by real-time PCR. Integration ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers. Integrated HPV16 viral load was defined as the product of HPV 16 viral load by the integration ratio. High HPV 16 viral load and high integration ratio were more frequent among women with squamous intraepithelial lesions compared with women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among women with high-grade squamous intraepithelial lesions compared with women without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs. 11%, respectively). High HPV 16 DNA load, but not high integration ratio, was also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%, respectively). The absence of statistical significance of these differences might be explained by the small study sample size. High-integrated HPV 16 DNA load was significantly associated with the presence of high-grade squamous intraepithelial lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may be considered as a useful marker of high-grade cervical lesions in HPV 16-infected women. (c) 2007 Wiley-Liss, Inc.

Freqüência de Neoplasia Intra-epitelial Cervical em Portadoras do Vírus da Imunodeficiência Humana Frequency of Cervical Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Women

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Antonio Pedro Flores Auge

2000-10-01

Full Text Available Objetivo: verificar a freqüência de neoplasia intra-epitelial cervical (NIC em mulheres infectadas pelo vírus da imunodeficiência humana (HIV. Métodos: foram estudadas 99 mulheres HIV-soropositivas; o diagnóstico da infeccão pelo HIV foi realizado por meio de dois testes ELISA, complementados por teste Western blot ou de imunofluorescência indireta. Como grupo controle foram analisadas 104 mulheres que não apresentavam positividade no teste ELISA. Em ambos os grupos o rastreamento de NIC foi realizado por meio da associação de colpocitologia oncológica e colposcopia. Nos casos em que a colposcopia revelou existência de zonas de transformação anormal, o diagnóstico de NIC foi realizado mediante biopsia dirigida, complementada ou não por conização. Resultados: em 15 das 99 pacientes do grupo de estudo (15,2% foi encontrada neoplasia intra-epitelial cervical, sendo dez casos de NIC I, um de NIC II e quatro de NIC III. Entre as 104 mulheres do grupo controle, quatro (3,8% eram portadoras de neoplasia intra-epitelial cervical, encontrando-se um caso de NIC I e três de NIC III. Conclusão: a análise comparativa dos resultados evidenciou que a freqüência de neoplasia intra-epitelial cervical foi significantemente mais elevada entre as pacientes infectadas pelo HIV.Purpose: to verify the frequency of cervical intraepithelial neoplasia in human immunodeficiency virus (HIV ¾ infected women. Methods: ninety-nine HIV-seropositive women were studied. The diagnosis of the HIV infection was established through two ELISA tests complemented by Western blot test or indirect immunofluorescence test. As control group, 104 women whose ELISA test was not positive were analyzed. The investigation of cervical intraepithelial neoplasia was achieved by association of Pap smear and colposcopy in both groups. In the cases where colposcopy revealed existence of abnormal transformation zones, NIC diagnosis was obtained through colposcopy-guided biopsy

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

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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...

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

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Florin STAMATIAN

2010-09-01

Full Text Available Objectives: Interleukin 4 plays a critical role in T helper 2 responses to HPV infection and angiogenesis. The present study aim to study the association between the IL4 promoter polymorphism – 590 C>T, respectively VNTR intron 2 polymorphism and cervical intraepithelial neoplasia. Material and method: We have realized a prospective case controls study that included 128 cases of intraepithelial neoplasia positive for HPV HR testing and 111 controls negative for intraepithelial lesion and also negative for HPV HR. Clinical examination was performed on each patient; blood and cervical sample were obtained. Cervical probes were analyzed regarding cytology and HPV HR testing. From peripheral blood DNA sample was obtain followed by genotype analysis for IL4 -590 C>T using PCR RFLP, respectively IL4 70 bp VNTR determined by PCR. Results: The absolute frequency of genotypes for IL4 -590 C>T was T/T-5, C/T-42, C/C-81 in the cases group respectively T/T-2, C/T-32, C/C-77 in the control group. The chi-square test had a value of 0.983 (p=0.321 while considering the presence of a minimum one single variant allele as a risk factor for cervical cancer, respectively 0.926 (p=0.336 for homozygous variant genotype. Odds ratio was 0.761 (95%CI [0.443-1.306] while considering C/T+T/T respectively 2R/3R, 2R/2R as a risk factor, and 0.451 (95%CI 95% [0.086-2.374] - TT respectively 2R/2R as a risk factor. Conclusion: No linear statistical significant association has been found between IL4 polymorphism and cervical neoplasia (p = 0.322.

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

NARCIS (Netherlands)

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

2018-01-01

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

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

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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

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...

Neoplasia intra-epitelial cervical: diagnóstico e tratamento Cervical intraepithelial neoplasia: diagnosis and treatment

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Sophie Françoise Mauricette Derchain

2005-07-01

Full Text Available O câncer do colo uterino é hoje doença passível de prevenção secundária. Os métodos de detecção das lesões precursoras e da infecção pelo papilomavírus humano, tais como a citologia oncológica e biologia molecular, são de uso mundialmente difundido. Entretanto, ainda há muita controvérsia em relação à aplicação destes métodos na prática ginecológica. Qual o melhor exame ou a melhor associação de exames que podem ser utilizados, com que intervalo e em quais mulheres permanecem questões que com freqüência geram ansiedade nos consultórios ou nas unidades de saúde. Por outro lado, uma vez detectada a infecção viral ou a neoplasia intra-epitelial cervical, o tratamento dessas mulheres ainda não é consensual e muitos fatores interferem na definição da conduta ótima. O tipo de infecção, gravidade da neoplasia intra-epitelial, tipo histológico encontrado, todos estes aspectos tendem a dificultar o planejamento terapêutico. Esta revisão tem como objetivo abordar, dentro do conhecimento atual e baseado nos consensos vigentes no país, vários aspectos relacionados ao rastreamento das lesões cervicais e as possíveis condutas terapêuticas vigentes.Cervical cancer is nowadays a disease amenable to secondary prevention. Methods for the detection of its precursor lesions and human papillomavirus infection, such as cervical cytology and molecular biology, achieved widespread use worldwide. However, there is still too much controversy regarding the use of these methods in gynecological practice. Which is the best examination or the best association of examinations, and the most adequate time intervals to proceed with screening, are still pending questions, generating anxiety in patients and doctors. On the other hand, the management of women who have been diagnosed with viral infection and/or cervical intraepithelial neoplasia is not yet consensual, and several factors may affect the clinical decision on how to

Immunostaining of p16INK4a/Ki-67 and L1 Capsid Protein on Liquid-based Cytology Specimens Obtained from ASC-H and LSIL-H Cases

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Byun, Seung Won; Lee, Ahwon; Kim, Suyeon; Choi, Yeong Jin; Lee, Youn Soo; Park, Jong Sup

2013-01-01

Background: Atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) are ambiguous diagnostic entities for the prediction of high-grade cervical lesion. Objective and reproducible tests for predicting high-grade cervical lesions are needed to reduce unnecessary colposcopic referrals or follow-ups. Objective: We aimed to identify an adequate set of adjunctive ...

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

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Ibáñez Raquel

2012-01-01

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

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

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

2018-02-01

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

Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

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Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

2007-01-01

Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH

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

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.

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

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

2018-01-01

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

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

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Wong, O G; Ho, M W; Tsun, O K; Ng, A K; Tsui, E Y; Chow, J N; Ip, P P; Cheung, A N

2018-03-26

To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions. © 2018 John Wiley & Sons Ltd.

Near-infrared Raman spectroscopy for assessing biochemical changes of cervical tissue associated with precarcinogenic transformation.

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Duraipandian, Shiyamala; Mo, Jianhua; Zheng, Wei; Huang, Zhiwei

2014-11-07

Raman spectroscopy measures the inelastically scattered light from tissue that is capable of identifying native tissue biochemical constituents and their changes associated with disease transformation. This study aims to characterize the Raman spectroscopic properties of cervical tissue associated with the multi-stage progression of cervical precarcinogenic sequence. A rapid-acquisition fiber-optic near-infrared (NIR) Raman diagnostic system was employed for tissue Raman spectral measurements at 785 nm excitation. A total of 68 Raman spectra (23 benign, 29 low-grade squamous intraepithelial lesions (LSIL) and 16 high grade squamous intraepithelial lesions (HSIL)) were measured from 25 cervical tissue biopsy specimens, as confirmed by colposcopy-histopathology. The semi-quantitative biochemical modeling based on the major biochemicals (i.e., DNA, proteins (histone, collagen), lipid (triolein) and carbohydrates (glycogen)) in cervical tissue uncovers the stepwise accumulation of biomolecular changes associated with progressive cervical precarcinogenesis. Multi-class partial least squares-discriminant analysis (PLS-DA) together with leave-one tissue site-out, cross-validation yielded the diagnostic sensitivities of 95.7%, 82.8% and 81.3%; specificities of 100.0%, 92.3% and 88.5%,for discrimination among benign, LSIL and HSIL cervical tissues, respectively. This work suggests that the Raman spectral biomarkers have identified the potential to be used for monitoring the multi-stage cervical precarcinogenesis, forming the foundation of applying NIR Raman spectroscopy for the early diagnosis of cervical precancer in vivo at the molecular level.

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

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

2013-01-01

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

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

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

2018-07-01

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

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

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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

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

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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

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

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McIntyre James A

2008-07-01

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

The detection of hTERC amplification using fluorescence in situ hybridization in the diagnosis and prognosis of cervical intraepithelial neoplasia: a case control study

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Yin Geping

2012-08-01

Full Text Available Abstract Background Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN and cervical cancer are Thinprep cytology test (TCT and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients’ prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC in the diagnosis and prognosis of CIN. Methods The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11 or radical surgery (n = 14. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH, and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. Results The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% ± 4.6% and 44.4% (12/27 respectively in patients with CIN I; 16.0% ± 14.4% and 85.1% (46/54 in patients with CIN II/III; 19.7% ± 13.3% and 88.3% (15 /17 in patients with carcinoma in situ; 47.0% ± 25.2% and 100% (28/28in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P Conclusion The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.

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

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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

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

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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.

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

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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

Vulvær intraepithelial neoplasi

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

2018-01-01

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

LOCALIZATION OF HUMAN PAPILLOMAVIRUS TYPE-16 DNA USING THE POLYMERASE CHAIN-REACTION IN THE CERVIX UTERI OF WOMEN WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

NARCIS (Netherlands)

Cornelissen, M. T.; van den Tweel, J. G.; Struyk, A. P.; Jebbink, M. F.; Briët, M.; van der Noordaa, J.; ter Schegget, J. T.

1989-01-01

The localization of human papillomavirus type 16 (HPV-16) DNA throughout the cervix uteri of women with cervical intraepithelial neoplasia (CIN) was studied by utilizing the polymerase chain reaction technique directly on histologically defined sections of paraffin-embedded cervical tissue obtained

Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ▿

OpenAIRE

Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-01-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CI...

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.

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

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Demarco, Maria; Lorey, Thomas S; Fetterman, Barbara; Cheung, Li C; Guido, Richard S; Wentzensen, Nicolas; Kinney, Walter K; Poitras, Nancy E; Befano, Brian; Castle, Philip E; Schiffman, Mark

2017-10-01

The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India

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Jaya Chakravarty

2016-01-01

Full Text Available Background & objectives: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART Centre in a tertiary care hospital in eastern India. Methods: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Results: Of the 216 HIV-positive women screened, 58 (26.85% were HPV-positive; 56 (25.9% were of high-risk (HR HPV type. The most prevalent HPV type was HPV-16 (7.9%; non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR, 2.56 (1.26-5.19], illiteracy [OR, 2.30 (1.19-4.46], rural residence [OR, 3.99 (1.27-12.56] and CD4 ≤350/µl [OR, 2.46 (1.26-4.83] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33% patients had normal/ negative for intraepithelial lesions (NILM cytology, three (1.60% had atypical squamous cells of undetermined significance (ASCUS, 32 (17.11% had low-grade squamous intraepithelial lesions (LSIL, 10 (5.35% had high-grade squamous intraepithelial lesions (HSIL and three (1.60% had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49] and CD4 ≤350/µl [OR, 2.84 (1.30-6.20] were risk factors for abnormal cytology. Interpretation &conclusions: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India.

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Chakravarty, Jaya; Chourasia, Ankita; Thakur, Minaxi; Singh, Abhishek Kumar; Sundar, Shyam; Agrawal, Nisha Rani

2016-01-01

India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤ 350/µl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤ 350/µl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

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

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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...

HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

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Oscar Peralta-Zaragoza

2013-01-01

Full Text Available Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

E6-associated transcription patterns in human papilloma virus 16-positive cervical tissues.

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Lin, Kezhi; Lu, Xulian; Chen, Jun; Zou, Ruanmin; Zhang, Lifang; Xue, Xiangyang

2015-01-01

The change in transcription pattern induced by post-transcriptional RNA splicing is an important mechanism in the regulation of the early gene expression of human papilloma virus (HPV). The present study was conducted to establish a method to specifically amplify HPV-16 E6-associated transcripts. The E6-related transcripts from 63 HPV-16-positive cervical tumor tissue samples were amplified, consisting of eight cases of low-risk intraepithelial lesions, 38 cases of high-risk intraepithelial lesions and 17 cases of cervical cancer (CxCa). The appropriate amplified segments were recovered following agarose gel electrophoresis, and subjected to further sequencing and sequence alignment analysis. Six groups of E6 transcription patterns were identified from HPV-16-positive cervical tumor tissue, including five newly-discovered transcripts. Different HPV-16 E6-associated transcription patterns were detected during the development of CxCa. Over the course of the progression of the low-grade squamous intraepithelial lesions to CxCa, the specific HPV-16 E6-associated transcription patterns and the dominant transcripts were all different. As indicated by this study, the transcription pattern of the E6 early gene of HPV-16 was closely associated with the stages of cervical carcinogenesis, and may also be involved in the development of CxCa.

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

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

2014-01-01

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

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

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

2014-05-01

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

Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.

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Hannah P Yang

Full Text Available Cervical intraepithelial neoplasia grade 3 (CIN3, the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.CIN3 cases varied substantially by size (1-10 LEEP segments and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.

Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix.

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Aires, G M A; Meireles, J R C; Oliveira, P C; Oliveira, J L; Araújo, E L; Pires, B C; Cruz, E S A; Jesus, N F; Pereira, C A B; Cerqueira, E M M

2011-01-01

We evaluated micronucleus and apoptosis occurrence among women with normal smears and women with different kinds of cervical abnormalities, i.e., inflammatory processes and low- and high-grade squamous intraepithelial lesions (N = 12, N = 10 and N = 27, respectively). The sample included 59 women who were seen at a public medical service for cervical cancer prevention in Feira de Santana, Bahia, Brazil. The diagnosis was established by means of cytological, colposcopic, and histopathological examination. Cytogenetic analysis was performed on 2000 cells from each woman and included assessment of micronuclei and nuclear degenerative abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed chromatin). Micronucleus frequency was significantly higher in the women with high-grade squamous intraepithelial lesions than in the women without cervical abnormalities or inflammatory processes (P 0.50), and significantly lower in women without cervical abnormalities and in women showing high-grade squamous intraepithelial lesions than in women showing inflammatory processes or low-grade squamous intraepithelial lesions (P cancer. The assessment of nuclear degenerative abnormalities indicative of apoptosis increased the sensitivity of this test.

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

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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.......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...

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

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

2018-01-01

precancer lesions. Here, we compare the cervical intraepithelial neoplasia grade 2 or worse (⩾CIN2) detection rate between non-attenders who participated in self-sampling and women attending routine screening. METHODS: A total of 23 632 women who were qualified as non-attenders in the Copenhagen Region were......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...... higher detection rates for ⩾CIN2 than routine cytology-based screening, and similar detection rates as HPV and cytology co-testing. This reinforces the importance of self-sampling for screening non-attenders in organised cervical cancer screening.British Journal of Cancer advance online publication, 14...

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

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Mei Chen

Full Text Available Tafazzin (TAZ is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27, high-grade squamous intraepithelial lesions (HSIL, n = 26 and squamous cervical carcinoma (SCC, n = 41 by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

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

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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

Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

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Cléber Sergio da Silva

2010-01-01

Full Text Available OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas. The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3, 35.5 (± 9.5, and 50 (± 11.2 years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3, cytotoxic lymphocytes (CD8, B lymphocytes (CD20, macrophages (CD68 and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control, at the intraepithelial lesion (CIN cases, and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05 in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05. CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma

NARCIS (Netherlands)

Sier, Cornelis F. M.; Zuidwijk, Kim; Zijlmans, Henry J. M. A. A.; Hanemaaijer, Roeland; Mulder-Stapel, Adri A.; Prins, Frans A.; Dreef, Enno J.; Kenter, Gemma G.; Fleuren, Gert Jan; Gorter, Arko

2006-01-01

Tumor progression and recurrence of cervical cancer is associated with upregulation of matrix metalloproteinase 2 (MMP-2). We evaluated the location, origin and activity of MMP-2 in cervical squamous cell carcinomas in comparison with MT1-MMP (MMP-14), TIMP-2 and extracellular matrix

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

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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

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

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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.

Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

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Ana Cristina Macêdo Barcelos

2011-01-01

Full Text Available Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL, or high-grade squamous intraepithelial lesion (HSIL. If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%, being 38 (54.2% reactive ASCUS and 32 (45.71% neoplastic ASCUS; 62 (88.5% ASC-US and 8 (11.41% ASC-H. ASCUS (Regione Protocol, respectively 1-5: 15 (21.4%, 19 (27.1%, 3 (27.1%, 16 (22.8%, and 1 (1.4%. A higher number of cases of cervical intraepithelial neoplasia (CIN II/III in the biopsies of patients with ASC-H compared to ASC-US (P=.0021. High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P=.031. Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

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

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

2018-04-13

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

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

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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

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.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

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De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

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

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

2016-10-01

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

Neoplasia intraepitelial cervical de alto grau durante a gestação: experiência de um serviço do Sul do Brasil High-grade cervical intraepithelial neoplasia during pregnancy: experience in a service in southern Brazil

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Vinícius Basso Preti

2009-12-01

Full Text Available 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 período gestacional e após o parto. Foram avaliados os diagnósticos de regressão e progressão das lesões. RESULTADOS: das 30 pacientes, 3 foram excluídas por não-confirmação do diagnóstico de lesão intraepitelial escamosa de alto grau (LEAG pela colposcopia com biópsia. Quatro pacientes foram submetidas ao tratamento durante a gestação, e uma delas apresentou parto pré-termo na 32ª semana de gestação. Vinte e três pacientes foram submetidas a tratamento expectante, realizando-se nova colposcopia e biópsia, sendo então submetidas à conização ou cirurgia de alta frequência em média na 11ª semana de gestação. Em 7,4% dos casos houve regressão da lesão na peça cirúrgica, embora a biópsia evidenciasse lesão de alto grau após o término da gestação. CONCLUSÕES: toda paciente com diagnóstico de lesão intraepitelial escamosa de alto grau (LEAG deve ser submetida à colposcopia e biópsia para excluir lesão invasiva. A conduta expectante para as lesões intraepiteliais é o tratamento de escolha e mais seguro pela possibilidade de regressão destas lesões no período pós-parto.PURPOSE: to evaluate the results of treatment to which patients with high grade intraepithelial cervical neoplasia (HSIL are submitted, as well as their follow-up during pregnancy. METHODS: retrospective study based on the review of the medical report of 30 patients with diagnosis of high-grade squamous intraepithelial lesions (HSIL during

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

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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

Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

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Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

2014-01-01

Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an

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

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Sonia Andersson

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

[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

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Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.

Characterization of a group of patients with cervical intraepithelial neoplasia diagnosed by diathermic loop biopsy

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Torriente Hernandez, Santa; Valdes Alvarez, Orlando; Villarreal Martinez, Aracelis; Lugo Sanchez, Ana

2011-01-01

A retrospective, longitudinal and descriptive study was conducted in 2 696 medical records corresponding to patients diagnosed with cervical intraepithelial neoplasia (CIN) and invasive cancer of cervix uteri (CCU) seen in the mother hospital of Guanabacoa municipality over above mentioned period. The information processing was from the data retrieval from medical records and biopsy control registry entering in a database in Microsoft Excel and the statistic processing using the SPSS package version 15 and EPIDAT

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

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

2018-01-01

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.

Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

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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...

[Factors associated with abnormal cervical cytology in pregnant women].

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Fan, Ling; Zou, Li-ying; Wu, Yu-mei; Zhang, Wei-yuan

2010-02-01

To investigate the risk factors associated with abnormal cervical cytology findings in pregnant women. From Sep. 2007 to Sep. 2008, 12,112 pregnant women who underwent their antenatal examinations at 12-36 gestational weeks in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. They were all excluded from the following pathologic obstetrics factors including threatened abortion, premature rupture of membranes or placental previa. Thinprep cytology test (TCT) were given at their first examination, meanwhile, a personal clinic file was established to record her occupation, education, address, family income, nationality, age of first intercourse, number of sex partners, contraception, marriage and pregnancy, current gynecologic diseases, family history of gynecologic tumors, history of gynecologic diseases and smoking and result of pelvic examination. Those risk factors leading to abnormal cervical cytology were analyzed. The complete clinical data were collected from 11 906 cases (98.30%, 11,906/12,112). It was found that 10,354 women were shown with normal TCT result, however, 1134 women (9.52%, 1134/11,906) with atypical squamous cells of undetermined significance (ASCUS), 112 women (0.94%, 112/11,906) with atypical glandular cells of undetermined significance (AGUS), 229 women (1.92%, 229/11,906) with low grade squamous intraepithelial (LSIL), 74 women (0.62%, 74/11,906) with high grade squamous intraepithelial (HSIL). Multiple factorial non-conditioned logistic regression analysis showed that age of first sexual intercourse (OR(ASCUS) = 2.90, OR(AGUS) = 7.32), number of sex partners (OR(ASCUS) = 1.49, OR(AGUS) = 2.02), number of abortion (OR(ASCUS) = 1.68, OR(AGUS) = 3.50) were correlated with ASCUS and AGUS. In LSIL group and HSIL group, age of first sexual intercourse (OR(LSIL) = 6.34, OR(HSIL) = 9.26), number of sex partners (OR(LSIL) = 1.69, OR(HSIL) = 1.65), number of abortion (OR(LSIL) = 1.53, OR(HSIL) = 5.33), smoking (OR(LSIL) = 1

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

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José E. Levi

Full Text Available 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% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

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

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Levi José E.

2002-01-01

Full Text Available 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% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia

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Lu Zhouping

2011-07-01

Full Text Available Abstract Background D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN has not been evaluated. Methods In this study, the immunoreactive patterns of D2-40, compared with p16INK4A, which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16INK4A immunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining. Results Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100% and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%. However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2% and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%. On the other hand, diffuse immunostaining for p16INK4A was shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16INK4A immunoreactivity. Conclusions Immunohistochemical analysis of D2-40 combined with p16INK4A may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.

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

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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)....

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

International Nuclear Information System (INIS)

Garcia-Iglesias, Trinidad; Daneri-Navarro, Adrian; Toro-Arreola, Alicia del; Albarran-Somoza, Benibelks; Toro-Arreola, Susana del; Sanchez-Hernandez, Pedro E; Ramirez-Dueñas, Maria Guadalupe; Balderas-Peña, Luz Ma. Adriana; Bravo-Cuellar, Alejandro; Ortiz-Lazareno, Pablo C

2009-01-01

Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression

The value of lymphoscintigraphy for cervical sentinel lymph node detection in patients with clinically N0 oral squamous cell carcinoma

International Nuclear Information System (INIS)

Liu Sheng; Jiang Ningyi; Lu Xianping; Liang Jiugen

2005-01-01

Objective: To evaluate the value of lymphoscintigraphy for cervical sentinel lymph node (SLN) detection in patients with oral squamous cell carcinoma. Methods: Twenty-one patients with clinically N 0 oral squamous carcinoma underwent preoperative lymphoscintigraphy and intraoperative methylene blue location. The results were compared with pathological findings. Results: 1) The sensitivity of lymphoscintigraphy for detecting SLN was 100%(21/21), and methylene blue was 85% (17/20). 2)Both SLN biopsy and cervical ablative dissection confirmed that 33.3% (7/21) patients were with cervical lymph node metastasis. Fourteen non-metastatic SLNs comfirmed by biopsy were also proved with the findings of neck dissection, and the specificity was 100%. Conclusion: Lymphoscintigraphy can detect the cervical SLN and accurately predict cervical lymph node metastasis in patients with oral squamous cell carcinoma.(authors)

Evaluation of a low-cost liquid-based Pap test in rural El Salvador: a split-sample study.

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Guo, Jin; Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Felix, Juan C

2014-04-01

We sought to test the diagnostic efficacy of a low-cost, liquid-based cervical cytology that could be implemented in low-resource settings. A prospective, split-sample Pap study was performed in 595 women attending a cervical cancer screening clinic in rural El Salvador. Collected cervical samples were used to make a conventional Pap (cell sample directly to glass slide), whereas residual material was used to make the liquid-based sample using the ClearPrep method. Selected samples were tested from the residual sample of the liquid-based collection for the presence of high-risk Human papillomaviruses. Of 595 patients, 570 were interpreted with the same diagnosis between the 2 methods (95.8% agreement). There were comparable numbers of unsatisfactory cases; however, ClearPrep significantly increased detection of low-grade squamous intraepithelial lesions and decreased the diagnoses of atypical squamous cells of undetermined significance. ClearPrep identified an equivalent number of high-grade squamous intraepithelial lesion cases as the conventional Pap. High-risk human papillomavirus was identified in all cases of high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and cancer as well as in 78% of low-grade squamous intraepithelial lesions out of the residual fluid of the ClearPrep vials. The low-cost ClearPrep Pap test demonstrated equivalent detection of squamous intraepithelial lesions when compared with the conventional Pap smear and demonstrated the potential for ancillary molecular testing. The test seems a viable option for implementation in low-resource settings.

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

OpenAIRE

Eli D. Ehrenpreis; Dylan G. Smith

2018-01-01

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

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia

International Nuclear Information System (INIS)

Ogino, Ichiro; Kitamura, Tatsuo; Okajima, Hiroyuki; Matsubara, Sho

1998-01-01

Purpose: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). Methods and Materials: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. Results: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. Conclusions: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy

Co-Testing of Cervical Screening Tests in Detection of High Grade Cervical Intraepithelial Neoplasia

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Smita Asthana

2017-10-01

Full Text Available Introduction: Co-testing performance for detection of high grade Cervical Intraepithelial Neoplasia (CIN has not been adequately addressed from Low Resource Countries (LRCs. Where isolated tests do not have adequate performance, further explorations are recommended. Aim: To evaluate the co-testing of conventional cervical screening tests such as Papanicolaou (Pap and Visual Inspection Cervix with Acetic Acid (VIA, with care HPV on Cervical Samples (CHPV or on Vaginal Samples (VHPV in the detection of high grade CIN. Materials and Methods: The cross-sectional study was conducted on ever married women of age 30 to 59 years in a rural community of Dadri. Women were screened by CHPV, VHPV, and Pap and VIA methods. Confirmation of screen positives was done by histology. Sensitivity, Specificity and likelihood ratios of different combinations of test determined to evaluate the performance. Results: Total eligible women, 66.2% (5032/7604 responded for screening. Analysis was performed on 4658, after excluding those who did not complete all screenings. Co-testing of CHPV (OR=246 or VHPV (OR=278 with Pap had highest association. Positive likelihood ratios of CHPV and VHPV with Pap in CIN II+ detection rates were 13.0 and 11.8 and in CIN III+ the detection rates were 18.0 and 16.0 respectively. Higher sensitivities and specificities were observed in co-testing for CIN III+ detection as against CIN II+ lesions. Conclusion: Choice of co-testing in a pair of tests for detection of high grade CIN is likely to depend on whether screening is targeted for developed or low resource country. VIA in isolation might not yield optimal results for LRCs.

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...

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

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......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...... the same HPV infections. Here, we determined the characteristics of the concordant (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30-65 years (n=2859) and in a concurrent referral population from the same...

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

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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.

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.

HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.

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Mark F Evans

Full Text Available 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: P<0.0001. These data are consistent with productive phase HPV 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

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.

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.

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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.

HPV 11, 16 and 18 DNA sequences in cervical swabs from women with cervical dysplasia: prevalence and associated risk of progression

DEFF Research Database (Denmark)

Hørding, U.; Daugaard, S.; Bock, J.E.

1991-01-01

Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

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.

Detection of human papillomavirus by hybrid capture and real time PCR methods in patients with chronic cervicitis and cervical intraepithelial

Directory of Open Access Journals (Sweden)

Elisha Khandker

2016-07-01

Full Text Available Background and objectives:Cervical cancer due to Human papillomavirus (HPV is one of the leading causes of morbidity and mortality in women. Testing of HPV can identify women who are at risk of cervical cancer. Nowadays, molecular methods like real time polymerase chain reaction (PCR and hybrid capture technique are applied for detecting HPV in cervical specimens. The objective of the present study was to determine the rate of HPV infection in women with chronic cervicitis and cervical intraepithelial neoplasia (CIN by a commercial real time polymerase chain reaction test kit and by a hybrid capture HPV DNA test. Methods:Women aged between 20 to 55 years with chronic cervicitis and CIN were enrolled in the study after obtaining informed consent. Cervical specimen was collected by using cervical brush and stored in transport medium until used. HPV was detected by High Risk Screen Real-TM Quant 2x (Sacace, Biotechnologies SrI, Italy real time PCR kit (HR RT-PCR and by Hybrid Capture-2 High-Risk HPV DNA (Hc-2; Digene Corporation, USA test. Results: Total 72 women with chronic cervicitis and CIN of different grades were included in the study. Out of this, HPV infection detected by HR RT-PCR was 31 (43% and by Hc-2 was 14 (19.4%. Both the tests were able to detect HPV infection in all the CIN 3 cases and in most of the CIN 2 cases. However, HR RT-PCR detected higher number of HPV in chronic cervicitis and CIN1 cases. Conclusion:The study has shown that HR RT-PCR and Hc-2 tests are equally effective in detecting HPV infection in patients with CIN 2 and CIN 3 lesions. However, HR RT-PCR is more sensitive test for detecting HPV in chronic cervicitis and early CIN lesions and, therefore can be used in epidemiological study to detect presence of HPV in general population. IMC J Med Sci 2016; 10(2: 45-48

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...

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

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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.

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

Science.gov (United States)

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

2011-01-01

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

Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012

DEFF Research Database (Denmark)

Baldur-Felskov, Birgitte; Munk, Christian; Nielsen, Thor Schütt Svane

2015-01-01

the Danish incidence trends during 1997-2011 when cervical screening coverage was high. Incidences of cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) were also assessed, with the latest part of the study period coinciding with introduction of free-of-charge human......PURPOSE: The incidence of cervical cancer, including squamous cell carcinoma (SCC), has been decreasing in several developed countries since the onset of organized screening programs; in some countries, however, the incidence of adenocarcinoma has increased among young women. We investigated......, importantly, they decreased significantly during 2009-2012 in women aged ≤20 years. CONCLUSIONS: The Danish screening program has successfully reduced the incidence of cervical cancer, especially of SCC in older women; however, the program has not significantly reduced the incidence in young women...

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.

Internal quality control indicators of cervical cytopathology exams performed in laboratories monitored by the External Quality Control Laboratory.

Science.gov (United States)

Ázara, Cinara Zago Silveira; Manrique, Edna Joana Cláudio; Tavares, Suelene Brito do Nascimento; de Souza, Nadja Lindany Alves; Amaral, Rita Goreti

2014-09-01

To evaluate the impact of continued education provided by an external quality control laboratory on the indicators of internal quality control of cytopathology exams. The internal quality assurance indicators for cytopathology exams from 12 laboratories monitored by the External Quality Control Laboratory were evaluated. Overall, 185,194 exams were included, 98,133 of which referred to the period preceding implementation of a continued education program, while 87,061 referred to the period following this intervention. Data were obtained from the Cervical Cancer Database of the Brazilian National Health Service. Following implementation of the continued education program, the positivity index (PI) remained within recommended limits in four laboratories. In another four laboratories, the PI progressed from below the limits to within the recommended standards. In one laboratory, the PI remained low, in two laboratories, it remained very low, and in one, it increased from very low to low. The percentage of exams compatible with a high-grade squamous intraepithelial lesion (HSIL) remained within the recommended limits in five laboratories, while in three laboratories it progressed from below the recommended levels to >0.4% of the total number of satisfactory exams, and in four laboratories it remained below the standard limit. Both the percentage of atypical squamous cells of undetermined significance (ASC-US) in relation to abnormal exams, and the ratio between ASC-US and intraepithelial lesions remained within recommended levels in all the laboratories investigated. An improvement was found in the indicators represented by the positivity index and the percentage of exams compatible with a high-grade squamous intraepithelial lesion, showing that the role played by the external quality control laboratory in providing continued education contributed towards improving laboratory staff skills in detecting cervical cancer precursor lesions.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

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Sheikhzadeh, Fahime; Ward, Rabab K; Carraro, Anita; Chen, Zhao Yang; van Niekerk, Dirk; Miller, Dianne; Ehlen, Tom; MacAulay, Calum E; Follen, Michele; Lane, Pierre M; Guillaud, Martial

2015-10-24

Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 μm below the epithelial surface were respectively 100, 100, and 92 %. Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical

Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia

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Chen Shaomin

2012-04-01

Full Text Available Abstract Background The amplification of oncogenes initiated by high-risk human papillomavirus (HPV infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions. Methods Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH using chromosome probes to TERC (3q26 and C-MYC (8q24. All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis. Results In the normal, cervical intraepithelial neoplasia grade 1 (CIN1, grade 2 (CIN2, grade 3 (CIN3 and squamous cervical cancer (SCC cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC cases than in the normal and CIN1 cases (p p p > 0.05. Conclusions The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.

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.

Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

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García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

2012-01-01

Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

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

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

2016-01-01

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

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

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Castellanos, Mario R; Szerszen, Anita; Gundry, Stephen; Pirog, Edyta C; Maiman, Mitchell; Rajupet, Sritha; Gomez, John Paul; Davidov, Adi; Debata, Priya Ranjan; Banerjee, Probal; Fata, Jimmie E

2015-07-25

Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.

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

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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 (<30, 30-39, 40-49, and ≥50 years) and age-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.

Squamous cell carcinoma antigen in serum for monitoring of head and neck and uterine cervical squamous cell carcinomas after radiotherapy

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Shirato, Hiroki; Ichimura, Wataru; Wakushima, Hiroshi; Nishioka, Takashi; Suzuki, Keishiro

1993-01-01

Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21 uterine cervical cancers), treated with radiotherapy. In 27 of the patients with head and neck cancer and in 12 of those with cervical cancer SCC-A had also been measured before radiotherapy. In this head and neck carcinoma group, the median level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI: 1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median SCC-A decreased significantly (p<0.001) from a pretreatment value of 7.5 (CI: 3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI:<0.5-1.8) ng/ml. In the total group of 75 head and neck cancers 21 relapses occurred and in 4 of these the relapse was detected at a clinically silent stage by an elevation of serum SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group of uterine cervical cancer. The study suggests that serum SCC-A may be useful for posttreatment monitoring of patients with uterine cervix cancer while its value in head and neck cancer probably is more marginal. (orig.)

Value and significance of tumor markers as CEA, CA125, SCC-Ag, CA199 and CYFRA21-1 in the diagnosis of cervical cancer

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Xiao-Juan Wang

2017-09-01

Full Text Available Objective: To investigate the value and significance of serum CEA, CA125, SCC-Ag, CA199 and CYFRA21-1 in the diagnosis of cervical cancer by comparing the detection of five serum markers. Methods: A total of 108 cases were divided into three groups, including 60 cervical cancerpatients and 20 cervical intraepithelial neoplasiain patients treated in our hospital from September 2015 to September 2016 and 28 healthy women. Radioimmunoassay was used to detect and compare the serum levels of CA125, CA199, CYFRA21-1 and ELISA method was used to detect and compare the serum levels of SCC-Ag, CEA. Results: (1 There was no statistically significant difference in the serum CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels between CIN group and control group. The serums CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels of cervical cancer patients were significantly higher than the other two groups. The differences were statistically significant. (2There were statistically significant differences in the serum CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels between different cervical pathological type groups.The serum CA125, CA199, CEA levels of cervical glandular cancer patients were significantly higher than the other two groups. The differences were statistically significant. The serum SCC-Ag, CYFRA21-1 levels of cervical squamous cancer patients were significantly higher than the other two groups. The differences were statistically significant. Conclusion: The serums CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels of cervical cancer patients were significantly higher than cervical intraepithelial neoplasiain patients and healthy women. The serum CA125, CA199, CEA levels of cervical glandular cancer patients were significantly higher and the serum SCC-Ag, CYFRA21-1 levels of cervical squamous cancer patients were significantly higher. The five tumor markers can be used in diagnosis of cervical cancer and they are also worthy in distinguishing cervical pathological types.

Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

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de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

2015-11-01

Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

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Kyung-Jin Min

2018-01-01

Full Text Available Background: 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. Methods: 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. Results: 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 <0.0003. Multivariate odds of <2 hours/day of 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. Conclusions: This study found that passive smoking among non-smoking women is associated with the risk of CIN 1.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

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Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Cervical cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) in four US-Affiliated Pacific Islands between 2007 and 2015.

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Senkomago, Virginia; Royalty, Janet; Miller, Jacqueline W; Buenconsejo-Lum, Lee E; Benard, Vicki B; Saraiya, Mona

2017-10-01

Cervical cancer incidence in the US-Affiliated Pacific Islands (USAPIs) is double that of the US mainland. American Samoa, Commonwealth of Northern Mariana Islands (CNMI), Guam and the Republic of Palau receive funding from the Centers for Disease Control (CDC) National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to implement cervical cancer screening to low-income, uninsured or under insured women. The USAPI grantees report data on screening and follow-up activities to the CDC. We examined cervical cancer screening and follow-up data from the NBCCEDP programs in the four USAPIs from 2007 to 2015. We summarized screening done by Papanicolaou (Pap) and oncogenic human papillomavirus (HPV) tests, follow-up and diagnostic tests provided, and histology results observed. A total of 22,249 Pap tests were conducted in 14,206 women in the four USAPIs programs from 2007-2015. The overall percentages of abnormal Pap results (low-grade squamous intraepithelial lesions or worse) was 2.4% for first program screens and 1.8% for subsequent program screens. Histology results showed a high proportion of cervical intraepithelial neoplasia grade 2 or worse (57%) among women with precancers and cancers. Roughly one-third (32%) of Pap test results warranting follow-up had no data recorded on diagnostic tests or follow-up done. This is the first report of cervical cancer screening and outcomes of women served in the USAPI through the NBCCEDP with similar results for abnormal Pap tests, but higher proportion of precancers and cancers, when compared to national NBCCEDP data. The USAPI face significant challenges in implementing cervical cancer screening, particularly in providing and recording data on diagnostic tests and follow-up. The screening programs in the USAPI should further examine specific barriers to follow-up of women with abnormal Pap results and possible solutions to address them. Published by Elsevier Ltd.

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era.

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Benard, Vicki B; Castle, Philip E; Jenison, Steven A; Hunt, William C; Kim, Jane J; Cuzick, Jack; Lee, Ji-Hyun; Du, Ruofei; Robertson, Michael; Norville, Scott; Wheeler, Cosette M

2017-06-01

A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

DNA-Cytometry of Progressive and Regressive Cervical Intraepithelial Neoplasia

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Antonius G. J. M. Hanselaar

1998-01-01

Full Text Available A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN, who had received follow‐up by cytology only. Automated image cytometry of Feulgen‐stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group. The second group of 26 smears with dysplastic changes had shown regression to normal (regressive group. The goal of the study was to determine if differences in cytometric features existed between the progressive and regressive groups. CIN categories I, II and III were represented in both groups, and measurements were pooled across diagnostic categories. Images of up to 700 intermediate cells were obtained from each slide, and cells were scanned exhaustively for the detection of diagnostic cells. Discriminant function analysis was performed for both intermediate and diagnostic cells. The most significant differences between the groups were found for diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells could be classified with 60% accuracy. Cytometric features which afforded the best discrimination were characteristic of the chromatin organization in diagnostic cells (nuclear texture. Slide classification was performed by thresholding the number of cells which exhibited progression associated changes (PAC in chromatin configuration, with an accuracy of 93 and 73% for diagnostic and intermediate cells, respectively. These results indicate that regardless of the extent of nuclear atypia as reflected in the CIN category, features of chromatin organization can potentially be used to predict the malignant or progressive potential of CIN lesions.

Population-based prevalence of abnormal cervical cytology findings and local risk factors in Ibadan, Nigeria: implications for cervical cancer control programs and human papilloma virus immunization.

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Thomas, J O; Ojemakinde, K O; Ajayi, I O; Omigbodun, A O; Fawole, O I; Oladepo, O

2012-01-01

To investigate the prevalence of abnormal cervical cytological findings and local risk factors in Ibadan, Nigeria. All women aged ≥15 years in each household in Idikan, Ibadan, were invited to participate in a population-based study. Structured questionnaires were administered to all consenting women. Conventional cervical Papanicolaou smears obtained from sexually active women were classified using the 2001 Bethesda system. The diagnoses were correlated with sociodemographic data and risk factors. Of 2,870 women aged ≥15 years estimated to live in Idikan, 1,204 sexually active women consented to pelvic examination and cervical smears. Results were available for 1,104 women (mean age: 39.8 years). Mean ages at menarche, first sexual intercourse and first pregnancy were 16.1, 20.3 and 20.7 years, respectively. Cytological results were categorized into atypical squamous cells of undetermined significance and atypical glandular cells 22 (1.99%); low-grade 43 (3.89%) and high-grade squamous intraepithelial lesions (HSIL) 17 (1.54%); invasive cancer 2 (0.18%) and normal 593 (53.8%) and reactive changes 427 (38.7%). The prevalence of epithelial abnormalities is 7.6%. Significant host-related factors in those with HSIL and invasive cancer included older age (mean 56.2 years), high parity and gravidity, lack of formal education and being divorced (p prevalence data and local risk factors for abnormal cervical cytology in a Nigerian population, which will be useful for planning future cervical cancer control programs. Copyright © 2012 S. Karger AG, Basel.

Prevalence of Human Papillomavirus Genotypes Among Women With High-Grade Cervical Lesions in Beijing, China

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Xiao, Meizhu; Xu, Qiuxiang; Li, Hongyan; Gao, Huiqiao; Bie, Yachun; Zhang, Zhenyu

2016-01-01

Abstract The aim of the study is to investigate the prevalence of high-risk human papillomavirus (hr-HPV) genotypes among Han women with high-grade cervical lesions in Beijing, China. Cervical cell specimens from patients with histopathologically confirmed cervical lesions at 7 hospitals in Beijing were examined with a validated HPV kit for 13 hr-HPV genotypes during the study period. The patients were divided into a low-grade cervical lesions group (cervical intraepithelial neoplasia grade 1, CIN1) and a high-grade cervical lesions group (CIN2+, including cervical intraepithelial neoplasia grade 2, CIN2; cervical intraepithelial neoplasia grade 3, CIN3; squamous cervical cancer, SCC; and adenocarcinoma of the cervix, ACC) based on the histopathology results. A total of 2817 eligible patients were enrolled, including 610 cases identified as CIN1 and 2207 as CIN2+. The hr-HPV positive rates in the CIN1 and CIN2+ groups were 78.2% (477/610) and 93.3% (2060/2207), respectively. The most frequently detected genotypes were HPV16, 58, 52 and18 in the CIN1 group and HPV16, 58, 33, and 52 in the CIN2+ group, in descending order of prevalence. In addition, the prevalence of HPV18 among the patients with ACC was 28.6% (14/49), significantly >7.2% (54/752) prevalence among the SCC patients (P HPV infections gradually deceased to 44.2% in the CIN2 patients, 36.7% in the CIN3 patients, and 35.3% in the cervical cancer (CC) patients, which included SCC and ACC patients. In cases of multiple hr-HPV infections in the CIN2+ group, double infections accounted for ∼76.6%, and HPV16+58, HPV16+52, and HPV16+18 were the most common combinations, in descending order. The most frequent combination for triple infections was HPV16+58+31, with a rate of 4.2%. The highest positive rate occurred in the ≤24 year-old group for all types of cervical lesions. The prevalence of HPV genotypes in the targeted population with high-grade cervical lesions differs from that of other countries. This

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance.

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Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

2015-03-01

Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated. Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034). Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

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

DEFF Research Database (Denmark)

Waldstrøm, Marianne; Ornskov, Dorthe

2011-01-01

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

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...

An institution-based cervical PAP smear study, correlation with clinical findings & histopathology in the Konkan region of Maharashtra state, India

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Bhushan M. Warpe

2016-08-01

Full Text Available Background: Cervical carcinoma is a common cause of death in India. It is presented by spectrum of precancerous lesions, called cervical intraepithelial neoplasia (CIN. Cervical cytological screening is designed to detect over 90% of cytological abnormalities. It has been established that cervical cancers can be diagnosed at the pre-invasive stage with adequate, repetitive cytological screening. Keeping in view of the importance of cervical PAP abnormalities & by classifying them by Bethesda terminology; correlation with clinical findings & histopathological findings was done. Methods: All cervical Pap smears reported in Department of Pathology from 1st August 2015 to 31st July 2016, were prospectively studied and classified according to revised Bethesda terminology, 2014. Also cytoradiological and clinico-cytological, cytohistological correlation was studied. Results: Due to increasing awareness among masses inculcated by social workers, most of the patients for PAP smear cytology came for routine screening to rule out cervical lesions followed by clinical finding of per-vaginal discharge. The 350 screened patients were in the third and fourth decades of life. 99/350 cases were subjected to USG study, with maximum number of cases (34 cases showing normal study, followed by cases with ovarian cysts and fatty liver disease. Negative for intra-epithelial lesion (NILM without any denotable organism was the pre-dominant cytological finding of PAP smear study followed by cases of NILM with bacterial vaginosis (30 cases with two malignancies. Intra-epithelial lesions (IELs were noted in 16.86%. ASCUS comprised 12.29%, ASC-H comprised 1.14%, L-SIL comprised 1.71%, HSIL comprised 1.43%, Atrophic cervical smears comprised 5.14%, Squamous cell carcinoma comprised 0.29% cases. ASC/LSIL ratio was 7.8 and inadequacy rate for PAP smear study was 7.43%. Cytologyhistopathology correlation was possible in 62 cases. Conclusion: Classification of cervical PAP

Prevalence and risk factors for cervical intraepithelial neoplasia in HIV-infected women in Salvador, Bahia, Brazil

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Paula Matos Oliveira

Full Text Available CONTEXT AND OBJECTIVE: The human immunodeficiency virus (HIV is frequently associated with high-grade intraepithelial neoplasia. Immunosuppression and high HIV viral load are the main risk factors for cervical intraepithelial neoplasia (CIN. The aim of this study was to determine the prevalence of CIN in HIV-infected women in Salvador, Bahia, Brazil, and to describe the risk factors in comparison with non-infected women. DESIGN AND SETTING: Cross-sectional study at the AIDS Reference Center of Bahia and the Gynecological Outpatient Clinic of Fundação Bahiana para o Desenvolvimento da Ciência, in Salvador, Bahia, Brazil. METHODS: Sixty-four HIV-infected women and 76 uninfected women from Salvador were enrolled between May 2006 and May 2007. Associations between CIN and presence of HIV infection, HIV viral load, proportion of T CD4+ lymphocytes and risk factors were evaluated. The independence of the risk factors was investigated using logistic regression. RESULTS: CIN was more prevalent among HIV-infected women than in the control group (26.6% versus 6.6%; P = 0.01. The odds ratio for CIN among HIV-infected women was 3.7 (95% confidence interval, CI: 1.23-11; P = 0.01, after adjusting for the following variables: age at first sexual intercourse, number of partners, number of deliveries and previous history of sexually transmitted disease. CONCLUSION: The prevalence of CIN among HIV-infected women was significantly higher than among women without HIV infection. HIV infection was the most important risk factor associated with the development of cervical lesions.

Cervical cytology and the diagnosis of cervical cancer in older women.

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Landy, Rebecca; Castanon, Alejandra; Dudding, Nick; Lim, Anita Wey Wey; Hollingworth, Antony; Hamilton, Willie; Sasieni, Peter D

2015-12-01

Most non-screen-detected cervical cancers are advanced stage. We assess the potential for cytology to expedite diagnosis when used outside of routine call and recall screening for cervical cancer. Two cohorts of women with cytology that did not appear to have been taken as part of routine screening, nested within a census of cervical cytology, in England between April 2007 and March 2010 were studied: 93,322 women aged 40-69 at first cytology, and 14,668 women aged ≥70. The diagnostic performance of high grade cervical squamous intraepithelial lesion (HSIL) or worse cytology was estimated. We also estimated case-fatality from stage distribution in women aged ≥66 with and without cytology in the year prior to diagnosis. There were 259 cancers diagnosed in women aged 40-69 at first cytology, and 78 in women aged ≥70. The sensitivity of cytology ≥ HSIL for cancer was 89% and 83% respectively, and the number of women needed to test to identify one cancer was 404 (95% confidence interval [CI]: 355-462) and 226 (95% CI: 177-292) respectively. Women aged ≥66 with cytology within a year of diagnosis had earlier stage cancers than those without, corresponding to a 17-22% reduction in case fatality. Cervical cytology is an excellent identifier of cancer among women tested outside routine screening call and recall. Its use as a triage tool, for instance in women with vague gynaecological symptoms, could facilitate earlier stage diagnosis and reduce cervical cancer mortality. © The Author(s) 2015.

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

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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.

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

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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.

The 2001 Bethesda System

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Bergeron Christine

2003-01-01

Full Text Available The Bethesda system is a system of terminology for reporting the results of cervical cytology. It was developed in 1988, and is now widely used in the United States. This system was updated in April 2001. The most important modifications are the following: a elimination of the category "satisfactory but limited by", b the reintegration of benign modifications in the normal category, c "atypical squamous cells of undetermined significance" is now named "atypical squamous cells" and subdivided into "atypical squamous cells of undetermined significance" and "cannot exclude high grade squamous intraepithelial lesion"; and d endocervical adenocarcinoma in situ which is now a separate entity. Low grade squamous intraepithelial lesions and high grade squamous intraepithelial cells remain unchanged. Recommendations have been proposed concerning automated review and ancillary testing.

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

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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

Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma.

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Cho, Oyeon; Chun, Mison; Oh, Young-Taek; Noh, O Kyu; Chang, Suk-Joon; Ryu, Hee-Sug; Lee, Eun Ju

2017-10-01

Radioresistance often leads to poor survival in concurrent chemoradiotherapy-treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan-Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0

Genotyping of the human papilloma virus in a group of Mexican women treated in a highly specialist hospital: Multiple infections and their potential transcendence in the current vaccination programme.

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Romero-Morelos, Pablo; Uribe-Jiménez, Arizbett; Bandala, Cindy; Poot-Vélez, Albros; Ornelas-Corral, Nora; Rodríguez-Esquivel, Miriam; Valdespino-Zavala, Mariana; Taniguchi, Keiko; Marrero-Rodríguez, Daniel; López-Romero, Ricardo; Salcedo, Mauricio

2017-10-11

Human papilloma virus (HPV) is one of the main risk factors associated with the development of cervical cancer and its precursor lesions. It has been reported that HPV16 and 18 types cover approximately 70% of cervical cancer worldwide; however, significant variation in percentages of HPV infections could be related to specific populations. Purified DNA of 67 cervical samples were analyzed by Linear Array® HPV genotyping kit. These analyzed samples correspond to 19 cervical tumors, 15 high-grade squamous intraepithelial lesions, 20 low-grade squamous intraepithelial lesions, and 13 cervical samples without injury were studied, all of them previously diagnosed. In general, 16 different HPV types were found with differences in their frequencies, cervical invasive cancer being the richest in HPV sequences, followed by the low-grade squamous intraepithelial lesions and then high-grade lesions. HPV16 was the most frequently distributed type in neoplastic lesions of the cervix, followed by the HPV52, suggesting viral type variability, probably associated to the geographical region studied. The results could indicate variability in HPV presence in Mexico, underlining the important role for HPV52 among others in the Mexican population. This would also potentially have an impact on the current anti-HPV vaccination schemes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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

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

2018-04-01

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

Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

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Tully, Stephen; Franceschi, Silvia

2017-01-01

Abstract Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa. Results. In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%–25%), up to 41%–47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa. Conclusions. HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women. PMID:28199532

Human papilloma virus infection and cervical dysplasia.

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Melinte-Popescu, Alina; Costăchescu, Gh

2012-01-01

Pap testing is considered to be the best screening tool for cervical cancer but there is currently great interest in the possible application of human papilloma virus (HPV) testing to supplement Pap screening for cervical cancer. To determine the prevalence of high-risk HPV types in the studied population and to explore the association between high-risk HPV types and cervical dysplasia. Cross-sectional study conducted at the Iasi Cuza Voda Obstetrics-Gynecology Hospital and Suceava County Hospital. 332 women who underwent colposcopy for cervical lesions between 2006 and 2011 were included in this study. The overall prevalence of HPV was 57.23%. HPV prevalence differs significantly in the three age groups up to 50 years. It was highest in patients below the age of 40 and progressively lower with advancing age. The overall prevalence of cervical dysplasia was 56.62%. The prevalence of cervical dysplasia was highest in the age groups up to 40 years. The most important determinant of HPV infection is age. Persistence of HPV appears to be associated with progression to squamous intraepithelial lesion. Dysplasia is often missed in a cervical sample either because of human error in screening and interpretation, or because of suboptimal quality of Pap smear. Incorporation of HPV testing into the present Pap screening program has the potential of making screening for cervical cancer more effective, and a necessary prelude to assessing this is by determining the prevalence of the high-risk types.

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

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

2014-04-08

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Down-regulation of the expression of CCAAT/enhancer binding protein α gene in cervical squamous cell carcinoma

International Nuclear Information System (INIS)

Pan, Zemin; Shao, Renfu; Zheng, Weinan; Zhang, Jinli; Gao, Rui; Li, Dongmei; Guo, Xiaoqing; Han, Hu; Li, Feng; Qu, Shen

2014-01-01

Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBPα gene in cervical cancer is still not clear. We investigated the expression of C/EBPα gene in cervical squamous cell carcinoma. C/EBPα mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBPα protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBPα gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBPα expression vector. C/EBPα expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays. There were significant difference in C/EBPα protein expression between chronic cervicitis and cervical carcinoma (P < 0.001). CEBPα mRNA level was significantly lower in cervical cancer tissues than in normal cervical tissues (P < 0.01). Methylation of the promoter of CEBPα gene in CpG 5, CpG-14.15, CpG-19.20 were significantly higher in cervical cancer than in normal cervical tissues (P < 0.05, P < 0.01, P < 0.05, respectively). CEBPα pcDNA3.1 construct transfected into HeLa cells inhibited cell proliferation and decreased cell migration. Our results indicate that reduced C/EBPα gene expression may play a role in the development of cervical squamous cell carcinoma

Oral Rigosertib for Squamous Cell Carcinoma

Science.gov (United States)

2017-06-22

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

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.

Clinical impact of atypical squamous cells of undetermined significance. A cytohistologic comparison.

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Lousuebsakul, V; Knutsen, S M; Gram, I T; Akin, M R

2000-01-01

To assess the percentage of squamous intraepithelial lesions (SILs) in the atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis. From January 1994 to December 1995, 421 cervical Pap smears with a diagnosis of ASCUS were followed with cervical biopsies within three months. The ASCUS cytologic diagnosis was correlated with the histologic findings and stratified according to age group, previous abnormal history and cell type of ASCUS (squamoid vs. metaplastic). Histologic diagnosis showed that of ASCUS diagnoses, 13% were normal, 34% were reactive, 4.8% were atypical, 43% were low grade SIL, 4% were high grade SIL, 1% were carcinoma in situ, and none were invasive lesions. The patients in the youngest group, up to 25 years, demonstrated the highest percentage of SIL. Patients with a previous abnormal gynecologic history showed a higher percentage of SIL than those without an abnormal history. SILs were observed in 51.5% of squamoid ASCUS and 36.5% of metaplastic ASCUS. Forty-eight percent of females having an ASCUS diagnosis on Pap smears had SIL and thus a preneoplastic lesion. The highest percentage of SIL was found in females 25 years and younger. Our findings suggest that an ASCUS diagnosis warrants ongoing follow-up.

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

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

2017-11-01

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

Increased incidence of cervical intraepithelial neoplasia in young women in the Mitte district, Berlin, Germany.

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Blohmer, J U; Schmalisch, G; Klette, I; Grineisen, Y; Kohls, A; Guski, H; Lichtenegger, W

1999-01-01

To investigate whether the incidence of cervical intraepithelial neoplasia (CIN), in particular of high grade CIN, increased in Berlin during the period 1970-1989 and whether the ages of women with CIN had decreased. In the former German Democratic Republic, which had a highly centralized public health system, all gynecologic operations performed on women living in the Mitte district of Berlin were carried out during the period 1970-1989 (when the Berlin Wall fell) in the gynecologic clinic of the Charité Hospital. The incidence of all CIN increased from year to year over the observation period: 0.04% (1970-1971), 0.10% (1980-1981), 0.39% (1988-1989). There was a particularly high increase in the incidence of high grade intraepithelial neoplasms (CIN 3): 0.016% (1970-1971), 0.056% (1980-1981), 0.25% (1988-1989). With a virtually unchanged age distribution for women in the Mitte district of Berlin, the median age of women with CIN 3 decreased significantly from 1970 to 1989, from 39.5 (1970) to 33 (1989) (P < .001). The increase in the incidence of CIN, especially of high grade CIN, as well as the reduction in age for onset of the disease, makes high participation in screening necessary, above all among young women.

The value of perfusion CT in predicting the short-term response to synchronous radiochemotherapy for cervical squamous cancer

International Nuclear Information System (INIS)

Li, Xiang Sheng; Fan, Hong Xia; Zhu, Hong Xian; Song, Yun Long; Zhou, Chun Wu

2012-01-01

To determine the value of the perfusion parameters in predicting short-term tumour response to synchronous radiochemotherapy for cervical squamous carcinoma. Ninety-three patients with cervical squamous carcinoma later than stage IIB were included in this study. Perfusion CT was performed for all these patients who subsequently received the same synchronous radiochemotherapy. The patients were divided into responders and non-responders according to short-term response to treatment. Baseline perfusion parameters of the two groups were compared. The perfusion parameters that might affect treatment effect were analysed by using a multivariate multi-regression analysis. The responders group had higher baseline permeability-surface area product (PS) and blood volume (BV) values than the non-responders group (P 0.05). At multivariate multi-regression analysis, BV, PS and tumour size were significant factors in the prediction of treatment effect. Small tumours usually had high PS and BV values, and thus had a good treatment response. Perfusion CT can provide some helpful information for the prediction of the short-term effect. Synchronous radiochemotherapy may be more effective in cervical squamous carcinoma with higher baseline PS and BV. (orig.)

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study.

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Astride Audirac-Chalifour

Full Text Available Cervical cancer (CC is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST. Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL and CC(p = 0.006, p = 0.036.When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006 and the largest distance compared to NCL-HPV negative ones (p<0.00001. The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.

Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

DEFF Research Database (Denmark)

Haupt, Richard M; Wheeler, Cosette M; Brown, Darron R

2011-01-01

The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were.......9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond...

Prevalence, risk factors, and pregnancy outcomes of cervical cell abnormalities in the puerperium in a hyperendemic HIV setting.

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Maise, Hopolang C; Moodley, Dhayendre; Sebitloane, Motshedisi; Maman, Suzanne; Sartorius, Benn

2018-01-01

To investigate the impact of cervical cell abnormalities detected in the puerperium in association with HIV-1 infection on pregnancy outcomes. The present study was a secondary data analysis of pregnancy outcomes, Pap smear results, HIV results, and participant demography from a behavioral intervention randomized controlled trial of 1480 pregnant women aged 18 years or more conducted at a periurban primary health clinic in South Africa during 2008-2010. The Pap smear was performed 14 weeks after delivery. In total, 564 (38.1%) women were HIV-1-positive and 78 (8.0%) of 973 women with a categorized Pap smear result tested positive for cervical cell abnormalities; 42 (4.2%) women had low-grade squamous intraepithelial lesions (LGSILs) and 7 (0.7%) had high-grade lesions (HGSILs). In an adjusted analysis, HIV infection was significantly more common among women with LGSILs (28/42 [66.7%]) or HGSILs (6/7 [85.7%]) when compared with the other Pap smear categories (P<0.001). The rates of premature birth, low birth weight, and non-live births were similar among HIV-infected and -uninfected women with abnormal cervical cytology. Pregnant women with HIV were more likely to be diagnosed with higher grades of squamous cell abnormalities than those without HIV. There was no association between squamous cell abnormalities/HIV comorbidity and adverse pregnancy outcomes. © 2017 International Federation of Gynecology and Obstetrics.

One-year follow-up of single-visit approach to cervical cancer prevention based on visual inspection with acetic acid wash and immediate cryotherapy in rural Thailand.

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Chumworathayi, B; Srisupundit, S; Lumbiganon, P; Limpaphayom, K K

2008-01-01

The aim is to evaluate 1) the visibility of cervical squamocolumnar junction (SCJ) after cryotherapy treatment and 2) to evaluate the effectiveness of cryotherapy treatment originally performed as part of a safety, acceptability, and feasibility (SAFE) demonstration project evaluating the SAFE of visual inspection with acetic acid (VIA) followed by immediate offer of cryotherapy among those who were tested positive and eligible for treatment. A total of 704 women presented at 1-year follow-up exam during which VIA was performed again by nurses. Six hundred and forty eight (92.0%) women received colposcopy and any kind of biopsy, if indicated, by trained physician colposcopists at a referral hospital. At 1 year, VIA nurses assessed 42 of 648 referred women (6.5%) as abnormal (test positive or suspected cancer). The SCJ was visible to the colposcopists in 91.7% (594/648) of the women. Among 42 women assessed as abnormal by the nurses, colposcopic findings were abnormal in 83.3% (35/42), with one low-grade squamous intraepithelial lesion, two high-grade squamous intraepithelial lesion (HSIL), and one adenocarcinoma confirmed later by biopsy. Among 606 VIA negative women, colposcopy was abnormal in only 23.4% (142/606), with two cases of HSIL confirmed later. Given that the SCJ was visible in the vast majority of women (91.7%) after cryotherapy, VIA could be used to provide follow-up for women previously treated. The disease negative rate after cryotherapy (no human papillomavirus infection, no cervical intraepithelial neoplasia, and no cancer) at 1 year after treatment was 85.5% (554/648).

Evaluation of 'see-see and treat' strategy and role of HIV on cervical cancer prevention in Uganda

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Sandin Sven

2010-05-01

Full Text Available Abstract Background There is scant information on whether Human Immunodeficiency Virus (HIV seropositivity has an influence on the outcome of treatment of precancerous cervical lesions using cryotherapy. We studied the prevalence of cervical abnormalities detectable by visual inspection and cervical lesions diagnosed by colposcopy according to HIV serostatus and described the outcomes of cryotherapy treatment. Methods Trained nurses examined women not previously screened for cervical cancer using visual inspection with acetic acid (VIA and Lugol's iodine (VILI in two family planning/post natal clinics in Kampala, Uganda, from February 2007 to August 2008. Women with abnormal visual inspection findings were referred for colposcopic evaluation and HIV testing. Women with precancerous cervical lesions detected at colposcopy were treated mainly by cryotherapy, and were evaluated for treatment outcome after 3 months by a second colposcopy. Results Of the 5 105 women screened, 834 presented a positive screening test and were referred for colposcopy. Of these 625 (75% returned for the colposcopic evaluation and were tested for HIV. For the 608 (97.5% women in the age range 20-60 years, colposcopy revealed 169 women with cervical lesions: 128 had inflammation, 19 had low grade squamous intraepithelial lesion (LGSIL, 13 had high grade squamous intraepithelial lesion (HGSIL, 9 had invasive cervical cancer and 2 had inconclusive findings. Detection rates per 1 000 women screened were higher among the older women (41-60 years compared to women aged 20-40 years. They were accordingly 55% and 20% for inflammation, 10% and 2% for LGSIL, 5% and 2% for HGSIL, 6% and 1% for invasive cervical cancer. Of the 608 women, 103 (16% were HIV positive. HIV positivity was associated with higher likelihood of inflammation (RR = 1.7; 95% CI: 1.2-2.4. Conclusions Detection rates were higher among older women 41-60 years. Visual inspection of the cervix uteri with acetic acid

Comparison of the accuracy of Hybrid Capture II and polymerase chain reaction in detecting clinically important cervical dysplasia: a systematic review and meta-analysis

International Nuclear Information System (INIS)

Luu, Hung N; Dahlstrom, Kristina R; Mullen, Patricia Dolan; VonVille, Helena M; Scheurer, Michael E

2013-01-01

The effectiveness of screening programs for cervical cancer has benefited from the inclusion of Human papillomavirus (HPV) DNA assays; which assay to choose, however, is not clear based on previous reviews. Our review addressed test accuracy of Hybrid Capture II (HCII) and polymerase chain reaction (PCR) assays based on studies with stronger designs and with more clinically relevant outcomes. We searched OvidMedline, PubMed, and the Cochrane Library for English language studies comparing both tests, published 1985–2012, with cervical dysplasia defined by the Bethesda classification. Meta-analysis provided pooled sensitivity, specificity, and 95% confidence intervals (CIs); meta-regression identified sources of heterogeneity. From 29 reports, we found that the pooled sensitivity and specificity to detect high-grade squamous intraepithelial lesion (HSIL) was higher for HCII than PCR (0.89 [CI: 0.89–0.90] and 0.85 [CI: 0.84–0.86] vs. 0.73 [CI: 0.73–0.74] and 0.62 [CI: 0.62–0.64]). Both assays had higher accuracy to detect cervical dysplasia in Europe than in Asia-Pacific or North America (diagnostic odd ratio – dOR = 4.08 [CI: 1.39–11.91] and 4.56 [CI: 1.86–11.17] for HCII vs. 2.66 [CI: 1.16–6.53] and 3.78 [CI: 1.50–9.51] for PCR) and accuracy to detect HSIL than atypical squamous cells of undetermined significance (ASCUS)/ low-grade squamous intraepithelial lesion (LSIL) (HCII-dOR = 9.04 [CI: 4.12–19.86] and PCR-dOR = 5.60 [CI: 2.87–10.94]). For HCII, using histology as a gold standard results in higher accuracy than using cytology (dOR = 2.87 [CI: 1.31–6.29]). Based on higher test accuracy, our results support the use of HCII in cervical cancer screening programs. The role of HPV type distribution should be explored to determine the worldwide comparability of HPV test accuracy

HPV testing and vaccination in Europe.

LENUS (Irish Health Repository)

Leeson, Simon C

2014-01-01

Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.

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

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Monica D Nye

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

NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Ma, Yue; Kong, Jienan; Yan, Guanghai; Ren, Xiangshan; Jin, Dan; Jin, Tiefeng; Lin, Lijuan; Lin, Zhenhua

2014-01-01

NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome 16q22, functions primarily to protect normal cells from oxidant stress and electrophilic attack. Recent studies have revealed that NQO1 is expressed at a high level in most human solid tumors including those of the colon, breast, pancreas, ovaries and thyroid, and it has also been detected following the induction of cell cycle progression and proliferation of melanoma cells. In this study, we aimed to investigate the clinicopathological significance of upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the uterine cervix. The localization of the NQO1 protein was determined in the SiHa cervical squamous cancer cell line using immunofluorescence (IF) staining, and immunohistochemical (IHC) staining performed on paraffin-embedded cervical SCC specimens from 177 patients. For comparison, 94 cervical intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1 mRNA expression levels, and HPV infection status was genotyped using oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall survival (OS) rates for all cervical SCC patients were calculated using the Kaplan–Meier method, and univariate and multivariate analysis was performed using the Cox proportional hazards regression model. The NQO1 protein showed a mainly cytoplasmic staining pattern in cervical cancer cells, and only three cases of cervical SCC showed a nuclear staining pattern. The strongly positive rate of NQO1 protein expression was significantly higher in cervical SCCs and CINs than in normal cervical epithelia. High-level NQO1 expression was closely associated with poor differentiation, late-stage, lymph node metastasis and high-risk for HPV infection. Additionally, high-level NQO1 expression was associated with lower DFS and 5-year OS rates, particularly for patients with early-stage cervical SCCs

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

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

International Nuclear Information System (INIS)

Linxweiler, Maximilian; Bochen, Florian; Schick, Bernhard; Wemmert, Silke; Al Kadah, Basel; Greiner, Markus; Hasenfus, Andrea; Bohle, Rainer-Maria; Juhasz-Böss, Ingolf; Solomayer, Erich-Franz; Takacs, Zoltan Ferenc

2016-01-01

Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology. Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers. FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure. Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential

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

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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.

Cytological analysis of atypical squamous epithelial cells of undetermined significance using the world wide web.

Science.gov (United States)

Washiya, Kiyotada; Abe, Ichinosuke; Ambo, Junichi; Iwai, Muneo; Okusawa, Estuko; Asanuma, Kyousuke; Watanabe, Jun

2011-01-01

The low-level consistency of the cytodiagnosis of uterine cervical atypical squamous epithelial cells of undetermined significance (ASC-US) employing the Bethesda System has been reported, suggesting the necessity of a wide survey. We presented cases judged as ASC-US on the Web and analyzed the voting results to investigate ASC-US cytologically. Cytology samples from 129 patients diagnosed with ASC-US were used. Images of several atypical cells observed in these cases were presented on the Web. The study, based on the voting results, was presented and opinions were exchanged at the meeting of the Japanese Society of Clinical Cytology. The final diagnosis of ASC-US was benign lesions in 76 cases and low- and high-grade squamous intraepithelial lesions in 44, but no definite diagnosis could be made for the remaining 9. The total number of votes was 17,884 with a 36.5% consistency of cases judged as ASC-US. Benign cases were divided into 6 categories. Four categories not corresponding to the features of koilocytosis and small abnormal keratinized cells were judged as negative for an intraepithelial lesion or malignancy at a high rate. A Web-based survey would be useful which could be viewed at any time and thereby facilitate the sharing of cases to increase consistency. Copyright © 2011 S. Karger AG, Basel.

Intracellular human papillomavirus E6, E7 mRNA quantification predicts CIN 2+ in cervical biopsies better than Papanicolaou screening for women regardless of age.

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Pierry, Deirdre; Weiss, Gerald; Lack, Benjamin; Chen, Victor; Fusco, Judy

2012-08-01

Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of ASCUS/LSIL triage in women including those younger than 30 years.

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

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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.

Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

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He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

2015-09-01

Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients.

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

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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.

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.

Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

International Nuclear Information System (INIS)

Mendoza-Catalán, Miguel A; Castañeda-Saucedo, Eduardo; Cristóbal-Mondragón, Gema R; Adame-Gómez, Jesús; Valle-Flores, Heidi N del; Coppe, José Fco; Sierra-López, Laura; Romero-Hernández, Mirna A; Carmen Alarcón-Romero, Luz del; Illades-Aguiar, Berenice

2012-01-01

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. 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). 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. 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

Prevalence of human papillomavirus types 11, 16 and 18 in cervical swabs. A study of 1362 pregnant women

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Hørding, U.; Iversen, A.K.N.; Sebbelov, A.

1990-01-01

Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med. mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

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

DEFF Research Database (Denmark)

Bottari, F; Sideri, M; Gulmini, C

2015-01-01

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......, 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...

Urothelial cells in smears from cervix uteri

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Palaoro, Luis Alberto; Guerra, Fernando; Angeleri, Anabela; Palamas, Marta; Melba, Sardi-Segovia; Rocher, Adriana Esther

2012-01-01

Objectives: To establish the cytological criteria to identify the urothelial cells in cervical smears in order to avoid mistakes in the cytological diagnosis. Materials and Methods: Cervical smears from 34 post menopausal women with vesicovaginal fistulas, advanced bladder prolapse and genital erosive lichen planes (vulvar kraurosis) (Group 1) and transitional cell metaplasia of the cervix (TCM, Group 2) were stained with Papanicolaou technique. The cervical samples were taken during the routine annual examination for prevention of the uterine cancer. Results: The smears of cervix from Group 1 showed urothelial cells from the three layers of the transitional epithelium. The umbrella cells are the bigger ones with relatively large nuclei. Frequently, they are multinucleated with single or multiple nucleoli and a typical “frothy” cytoplasm (cytoplasmic vacuoles). The cells of the Group 2 showed nuclei with oval to spindled shapes, some tapered ends, less cytoplasm than squamous metaplastic cells, powdery chromatin, small nucleoli and nuclear grooves. Conclusions: The umbrella cells may be mistaken for dysplastic cells originating in low grade squamous intraepithelial lesions lesions (LSILs) due to their nuclear and cytoplasm sizes. Therefore, it is important to know the possibility of their appearance in the cervical smears, especially in post menopausal patients in order to avoid a false diagnosis of an intraepithelial lesion. It is unlikely that deeper cells of urothelium would be confused with high grade squamous intraepithelial lesion (HSIL) cells. However, their presence might be a reason of mistake in the diagnosis. TCM is an under-recognized metaplastic phenomenon of the cervix and vagina, which is a mimicker of high-grade squamous intraepithelial lesion. The differential characteristic between umbrella cells, cells from TCM and the deeper urothelial cells, and LSIL and HSIL are detailed in the present paper. PMID:22438615

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

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

2015-01-01

with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18......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...

NOVEL EPIGENETIC CHANGES IN CDKN2A ARE ASSOCIATED WITH PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA

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Wijetunga, N. Ari; Belbin, Thomas J.; Burk, Robert D.; Whitney, Kathleen; Abadi, Maria; Greally, John M.; Einstein, Mark H.; Schlecht, Nicolas F.

2016-01-01

Objective To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16INK4A and p14ARF proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. Methods We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. Results In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Conclusion Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16INK4A/p14ARF expression prior to development of malignant disease. PMID:27401842

Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia.

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Wijetunga, N Ari; Belbin, Thomas J; Burk, Robert D; Whitney, Kathleen; Abadi, Maria; Greally, John M; Einstein, Mark H; Schlecht, Nicolas F

2016-09-01

To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16(INK4A)/p14(ARF) expression prior to development of malignant disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of occult cervical lymph node metastasis in primary squamous cell carcinoma of the head and neck by computed tomography

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Shakil, U.

2015-01-01

To determine the frequency of occult (node negative) cervical lymph node metastasis in primary head and neck squamous cell carcinoma, using contrast enhanced computed tomography (CT). Study Design: Cross sectional descriptive study. Place and Duration of Study: Study was conducted in Department of Radiology, Combined Military Hospital Rawalpindi. Duration of the study was 06 months i.e. from 19th February 2011 to 19th August 2011. Patients and Methods: A total of 141 cases, fulfilling the inclusion criteria, reporting to the radiology department, were included in the study after seeking written informed consent. All patients underwent contrast enhanced CT scan of the neck from base of skull to root of neck using Asteion Whole Body X-ray CT Scanner (Model TSX-021A). Images were evaluated for the presence or absence of cervical lymph node metastasis according to the cervical lymph node metastatic criteria at each level of the neck. Results: Of the 141 patients with clinically no head and neck squamous cell carcinoma, 45.4% were found to have lymph node metastases. Frequency of occult metastases in squamous cell carcinoma of oral cavity was 47.6%, oropharynx 23.5%, larynx 33.3% and hypopharynx 78.6%. Conclusion: In clinically node negative neck, the risk of lymph node metastases is significantly high in patients of head and neck squamous cell carcinoma in our population. All patients presenting with node negative neck should undergo CT scans for early detection of occult metastasis. (author)

Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark

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Kjaer, Susanne K.; Breugelmans, Gabrielle; Munk, Christian

2008-01-01

/11. Prevalence of high-risk HPV types increased from 19.2% in women with normal cytology to 100% in women with cervical intraepithelial neoplasia grade 3 (CIN3)/cervical cancer. HPV 16 was the most prevalent type (6.0% of all women), and was also the most prevalent in women with HSIL (35.1%) and CIN3 (53......-grade squamous intraepithelial lesion and 1.6% had high-grade squamous intraepithelial lesion (HSIL). The HPV prevalence was 26.4% with a peak in women 20-24 years (50.2%) and then decreased without a second peak in older women. Among the youngest women (15-19 years), 14% had HPV 16/18 and 16% had HPV 6.......2%). Other common HPV types in women with CIN3 included HPV 52, 51, 31, 33 and 18. HPV 16/18 alone was present in 23% of CIN3 lesions and 67% of cervical cancers, and HPV 16/18 together with other high-risk HPV types was present in 41% of CIN3 lesions. This suggests that an efficacious HPV 16/18 vaccine...

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

Interobserver reproducibility of the histological diagnosis of cervical dysplasia, Hospital San Juan de Dios, from January to December 2010

International Nuclear Information System (INIS)

Morales Navarro, Karla Andrea

2013-01-01

The reproducibility of the histological diagnosis of cervix specimens processed by the Pathology Service of the San Juan de Dios Hospital from January to December 2010 was determined. When operational failures were detected, possible improvement processes were proposed, guided by the study's findings. A moderate concordance for the Bethesda System and poor to moderate for the classification of Cervical Intraepithelial Neoplasia, was obtained after analyzing the diagnoses issued by the observers when comparing the pairs of pathologists. The concordance was moderate when comparing each pathologist with the standard for both classifications. The correlation was excellent when comparing the Classification Cervical Intraepithelial Neoplasia versus the Bethesda System. The categories with highest concordance were high-grade intraepithelial lesion and cervical intraepithelial neoplasia 3 and minor agreement were low-grade intraepithelial lesion and cervical intraepithelial neoplasia 2. The results agree and in some cases the results exceed the reproduction noted in the literature world medical [es

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

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Cacilda Tezelli Junqueira Padovani

2013-06-01

Full Text Available Introduction The progression of human papillomavirus (HPV infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment. Methods We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes. Results We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8% was predominant in samples with ≥1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL samples (p = 0.16. CD25 was present in great quantities in all samples. Conclusions The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.

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.

HPV infection in women with and without cervical cancer in Conakry, Guinea.

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Keita, N; Clifford, G M; Koulibaly, M; Douno, K; Kabba, I; Haba, M; Sylla, B S; van Kemenade, F J; Snijders, P J F; Meijer, C J L M; Franceschi, S

2009-07-07

Cervical cancer incidence in western Africa is among the highest in the world. To investigate human papillomavirus (HPV) infection in Guinea, we obtained cervical specimens from 831 women aged 18-64 years from the general population of the capital Conakry and from 77 locally diagnosed invasive cervical cancers (ICC). Human papillomavirus was detected using a GP5+/6+ PCR-based assay. Among the general population, the prevalence of cervical abnormalities was 2.6% by visual inspection and 9.5% by liquid-based cytology. Fourteen of 15 high-grade squamous intraepithelial lesions were visual inspection-negative. Human papillomavirus prevalence was 50.8% (32.1% for high-risk types) and relatively constant across all age groups. Being single or reporting > or =3 sexual partners was significantly associated with HPV positivity. HPV16 was the most common type, both among the general population (7.3%) and, notably in ICC (48.6%). HPV45 (18.6%) and HPV18 (14.3%), the next most common types in ICC, were also more common in ICC than in HPV-positive women with normal cytology from the general population. The heavy burden of HPV infection and severe cervical lesions in Guinean women calls for new effective interventions. Sixty-three per cent of cervical cancers are theoretically preventable by HPV16/18 vaccines in Guinea; perhaps more if some cross-protection exists with HPV45.

Human papillomavirus infection of the cervix uteri in women attending a Health Examination Center of the French social security.

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Beby-Defaux, A; Bourgoin, A; Ragot, S; Battandier, D; Lemasson, J M; Renaud, O; Bouguermouh, S; Vienne Md, Maladie de la; Agius, G

2004-06-01

Since human papillomavirus (HPV) is the central causal factor in cervical cancer, understanding the epidemiology of this infection constitutes an important step towards development of strategies for prevention. Six hundred and fifty seven cervical samples were tested for HPV using PCR with consensus primers (MY09/MY11), by genotyping (restriction and sequencing analyses) and by cervical cytology, from women who attended a Health Examination Center of the French social security. Women with no cervical smear as well as women with cytological abnormalities within the last 3 years were recruited. HPV DNA was detected in 7.3% of the women (5.3% for high-risk, 2.4% for low-risk, and 0.5% for unknown risk types) including 6 (0.9%) mixed infections. Fifteen different genotypes were detected, of which genotypes 16 (22.2%), 58 (13.0%), 18 (11.1%), 30 (9.2%), and 33 (9.2%) were the most prevalent. In age group 17-25 years, we found the highest frequencies for both any (22.1%) and high-risk (14.7%) HPV, and prevalences gradually decreased with age. 5.2% of low-grade squamous intraepithelial lesion, 0.3% of high-grade squamous intraepithelial lesion, and 1.2% of atypical squamous cells of undetermined significance were found. The frequencies of high risk and all HPV types were significantly higher in squamous intraepithelial lesions than in those with normal and reactive/reparative changes (P < 0.0001). The prevalence of high-risk HPV in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion group (28.6%) was significantly higher than in the normal and reactive/reparative changes groups (3.4%) (P < 0.0001). HPV detection was associated with younger age, single marital and non-pregnant status (P < 0.0001), premenopausal status (P = 0.0004), and contraception (P = 0.0008). Marital status (OR 4.5; 95% CI = 2.3-9.0) and tobacco consumption (OR 3.0; 95% CI = 1.6-5.7) were predictive independent factors of HPV infection. The French system

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings.

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Yamal, Jose-Miguel; Zewdie, Getie A; Cox, Dennis D; Atkinson, E Neely; Cantor, Scott B; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P H; Follen, Michele

2012-04-01

Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training.

Suppressor of fused (Sufu) promotes epithelial-mesenchymal transition (EMT) in cervical squamous cell carcinoma

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Zhang, Ziyu; Zou, Yang; Liang, Meirong; Chen, Yuanting; Luo, Yong; Yang, Bicheng; Liu, Faying; Qin, Yunna; He, Deming; Wang, Feng; Huang, Ouping

2017-01-01

Suppressor of fused is essential for the maximal activation of Sonic Hedgehog signaling in development and tumorigenesis. However, the role of Sufu in cervical carcinoma remains unknown. Here, we report new findings of Sufu in regulating the epithelial-to-mesenchymal transition through the FoxM1 transcriptional modulation by 14-3-3ζ protein in cervical carcinoma. Sufu is overexpressed in cervical squamous cell carcinoma and its level in clinical tumor tissues is positively correlated with 14-3-3ζ. Functionanlly, siSufu remarkably prevents the cancer cell migration and invasion. We further demonstrate that the transcriptional activity of Sufu is increased by FoxM1, of which stability is promoted by 14-3-3ζ. Knockdown FoxM1 decreases the invasion of SiHa cells and reconstitution of Sufu rescues the invasion of these cells.Finally, overexpression of Sufu is significantly associated with differentiation grade, FIGO stage, Depth of stromal invasion and vascular cancer embolus. Our findings highlight a novel role for Sufu in cervical carcinogenesis. PMID:29371981

Geometrical nuclear diagnosis and total paths of cervical cell evolution from normality to cancer

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Javier Oswaldo Rodríguez Velásquez

2015-01-01

Full Text Available Background: The diagnosis of cervix cytology has problems of inter-observer reproducibility. Methodologies based on fractal geometry objectively differentiated normal, low-grade squamous intraepithelial lesion (L-SIL and high-grade squamous intraepithelial lesion (H-SIL states. Aims: The aim was to develop a mathematical-physical diagnosis and a theoretical generalization of the evolution paths of cervical cells from normal to carcinoma based on their occupation in the box-counting space. Subjects and Methods: Overlaying a grid of 8x8 pixels, the a number of squares occupying the nucleus surface and cytoplasm of 5 normal cells, 5 ASCUS, 5 L-SIL and 5 H-SIL were evaluated, as well as the ratio C/N, establishing differences between states. Sensitivity, specificity, negative likelihood ratio, and Kappa coefficient over the gold standard were calculated. Also was developed a generalization of all possible paths from normality to carcinoma. Results: The occupancy spaces of the nuclear surface allow differentiating normal L-SIL and H-SIL thus avoiding the indeterminacy of ASCUS cells. Compared to the Gold Standard, this method has sensitivity and specificity of 100%, negative likelihood ratio of 0, and Kappa coefficient of 1. 62,900 possible routes of evolution were determined between normal and H-SIL, states, based on the structural basis of the cells. Conclusions: it was obtained an objective and reproducible diagnostic methodology of the development of preneoplastic and neoplastic cervical cells for clinical application. Additionally were developed all possible paths of preneoplastic cellular alteration to carcinoma which facilitates the tracking of patients over time to clinical level, warning of alterations that lead to malignancy, based on the spatial occupation measurements of the nucleus in fractal space regardless of causes or risk factors.

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

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Stanley Margaret A

2012-09-01

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

Human papillomavirus DNA detection in menstrual blood from patients with cervical intraepithelial neoplasia and condyloma acuminatum.

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Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-03-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases.

Association between human papillomavirus and Epstein - Barr virus DNA and gene promoter methylation of RB1 and CDH1 in the cervical lesions: a transversal study.

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McCormick, Thaís M; Canedo, Nathalie H S; Furtado, Yara L; Silveira, Filomena A; de Lima, Roberto J; Rosman, Andréa D F; Almeida Filho, Gutemberg L; Carvalho, Maria da Glória da C

2015-06-02

Human papillomavirus (HPV) inactivates the retinoblastoma 1 (RB1) gene by promoter methylation and reduces cellular E-cadherin expression by overexpression of DNA methyltransferase 1 (DNMT1). The Epstein-Barr virus (EBV) is an oncogenic virus that may be related to cervical carcinogenesis. In gastric cancer, it has been demonstrated that E-cadherin gene (CDH1) hypermethylation is associated with DNMT1 overexpression by EBV infection. Our aim was to analyze the gene promoter methylation frequency of RB1 and CDH1 and verify the association between that methylation frequency and HPV and EBV infection in cervical lesions. Sixty-five samples were obtained from cervical specimens: 15 normal cervices, 17 low-grade squamous intraepithelial lesions (LSIL), 15 high-grade squamous intraepithelial lesions (HSIL), and 18 cervical cancers. HPV and EBV DNA testing was performed by PCR, and the methylation status was verified by MSP. HPV frequency was associated with cervical cancer cases (p = 0.005) but not EBV frequency (p = 0.732). Viral co-infection showed a statistically significant correlation with cancer (p = 0.027). No viral infection was detected in 33.3% (5/15) of controls. RB1 methylated status was associated with cancer (p = 0.009) and HPV infection (p = 0.042). CDH1 methylation was not associated with cancer (p = 0.181). Controls and LSIL samples did not show simultaneous methylation, while both genes were methylated in 27.8% (5/18) of cancer samples. In the presence of EBV, CDH1 methylation was present in 27.8% (5/18) of cancer samples. Only cancer cases presented RB1 promoter methylation in the presence of HPV and EBV (33.3%). The methylation status of both genes increased with disease progression. With EBV, RB1 methylation was a tumor-associated event because only the cancer group presented methylated RB1 with HPV infection. HPV infection was shown to be significantly correlated with cancer conditions. The global methylation frequency was

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

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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.

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

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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.

Rastreamento anterior para câncer de colo uterino em mulheres com alterações citológicas ou histológicas Previous screening for cervical cancer among women with cytological and histological abnormalities

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C Rama

2008-06-01

do último exame citológico anterior.OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15-65 years old who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson's chi-was conduted square test at a 5% significance level. RESULTS: Cytological abnormalities were found in 354 women (6.4% and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7% were normal results. Colposcopy was performed in 289 women, and 145 (50.2% showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6% of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9% of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5% and 92.8% of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically significant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology.

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

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Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

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

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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.

[High-risk human papilloma virus and cervical intraepithelial neoplasia in women at 2 hospitals in Mexico City].

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Hernández-Hernández, Dulce Ma; García-Carrancá, Alejandro; Guido-Jiménez, Miriam C; González-Sánchez, José Luis; Cruz-Talonia, Fernando; Apresa-García, Teresa; Martínez-Elizondo, Olga A; Ornelas-Bernal, Laura; Alvarado-Cabrera, Isabel; Muñoz, Sergio

2002-01-01

To determine the high risk HPV (HR-HPV) association with Cervical Intraepithelial Neoplasia (CIN) in women of two Dysplasia Clinics in Mexico City. Prolective case-control study was done. Women with and without security affiliation attended in Instituto Mexicano del Seguro Social (Hospital 1) and Hospital General de México (Hospital 2) were included in the study. Cases were women with histopathologic diagnosis of CIN and controls were women with negative dysplasia in cytologic study (Pap). Information was obtained by direct interview. HR-HPV was determined by Hybrid Capture II assay, in cervical samples. Bivariate and logistic regression analysis was done. One hundred and two cases and 192 controls from Hospital 1 and 89 cases and 66 controls from Hospital 2 were included. 83.3% and 77.3% of women from Hospital 1 and 2 respectively were positive to HR-HPV. The association HR-HPV and CIN in Hospital 1 was ORa = 40.6, C.I. 95% = 17-96.8; while in Hospital 2 there was not association. Age was an effect modifier in the HR-HVP and CIN association, in Hospital 1. It was observed a correlation between viral load and CIN degree. The HR-HPV infection frequency in controls and CIN I was higher than the reported in other studies. Age was a modifier in the HR-HPV association and CIN. In dysplasia clinics without medical referral system of patients is possible to observe similar risk factors to cervical cancer.

The effectiveness of acetic acid wash protocol and the interpretation patterns of blood contaminated cervical cytology ThinPrep® specimens

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Nora K Frisch

2015-01-01

Full Text Available Background: ThinPrep® (TP cervical cytology, as a liquid-based method, has many benefits but also a relatively high unsatisfactory rate due to debris/lubricant contamination and the presence of blood. These contaminants clog the TP filter and prevent the deposition of adequate diagnostic cells on the slide. An acetic acid wash (AAW protocol is often used to lyse red blood cells, before preparing the TP slides. Design: From 23,291 TP cervical cytology specimens over a 4-month period, 2739 underwent AAW protocol due to initial unsatisfactory smear (UNS with scant cellularity due to blood or being grossly bloody. Randomly selected 2739 cervical cytology specimens which did not undergo AAW from the same time period formed the control (non-AAW group. Cytopathologic interpretations of AAW and non-AAW groups were compared using the Chi-square test. Results: About 94.2% of the 2739 cases which underwent AAW were subsequently satisfactory for evaluation with interpretations of atypical squamous cells of undetermined significance (ASCUS 4.9% (135, low-grade squamous intraepithelial lesions (LSIL 3.7% (102, and high-grade squamous intraepithelial lesions (HSIL 1% (28. From the 2739 control cases, 96.3% were satisfactory with ASCUS 5.5% (151, LSIL 5.1% (139, and HSIL 0.7% (19. The prevalence of ASCUS interpretations was similar (P = 0.33. Although there were 32% more HSIL interpretations in the AAW group (28 in AAW vs. 19 in non-AAW, the difference was statistically insignificant (P = 0.18. AAW category; however, had significantly fewer LSIL interpretations (P = 0.02. The percentage of UNS cases remained higher in the AAW group with statistical significance (P < 0.01. Conclusions: While AAW had a significantly higher percent of UNS interpretations, the protocol was effective in rescuing 94.2% of specimens which otherwise may have been reported unsatisfactory. This improved patient care by avoiding a repeat test. The prevalence of ASCUS and HSIL

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

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

2009-01-01

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

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.

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

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

2009-01-01

Background 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. Results 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. Conclusion 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. PMID:19216802

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.

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

2017-11-01

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

Validity and reliability of using a self-lavaging device for cytology and HPV testing for cervical cancer screening: findings from a pilot study.

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Heidi E Jones

Full Text Available Self-sampling could increase cervical cancer screening uptake. While methods have been identified for human papillomavirus (HPV testing, to date, self-sampling has not provided adequate specimens for cytology. We piloted the validity and reliability of using a self-lavaging device for cervical cytology and HPV testing. We enrolled 198 women in New York City in 2008-2009 from three ambulatory clinics where they received cervical cancer screening. All were asked to use the Delphi Screener™ to self-lavage 1-3 months after clinician-collected index cytological smear (100 normal; 98 abnormal. Women with abnormal cytology results from either specimen underwent colposcopy; 10 women with normal results from both specimens also underwent colposcopy. We calculated sensitivity of self-collected cytology to detect histologically confirmed high grade lesions (cervical intraepithelial neoplasia, CIN, 2+; specificity for histology-negative (CIN 1 or lower, paired cytology negative, or a third cytology negative; and kappa for paired results. One hundred and ninety-seven (99.5% women self-collected a lavage. Seventy-five percent had moderate to excellent cellularity, two specimens were unsatisfactory for cytology. Seven of 167 (4% women with definitive results had CIN2+; one had normal and six abnormal cytology results with the self-lavage (sensitivity = 86%, 95% Confidence Interval, CI: 42, 100. The kappa for paired cytology was low (0.36; 95% CI: 0.25, 0.47 primarily due to clinician specimens with atypical squamous cells of undetermined significance (ASC-US and low grade squamous intraepithelial lesion (LSIL coded as normal using Screener specimens. However, three cases of HSIL were coded as ASC-US and one as normal using Screener specimens. Seventy-three women had paired high-risk HPV tests with a kappa of 0.66 (95% CI: 0.49, 0.84. Based on these preliminary findings, a larger study to estimate the performance of the Screener for co-testing cytology and

Cervical intraepithelial neoplasia; Residual and recurrent disease after laser surgery. Cervikal intraepitelial neoplasi; Persistens og residiv etter laserbehandling

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Forsmo, S.; Oeian, P.; Stalsberg, H. (University and Regional Hospital, Tromsoe (Norway))

1992-03-01

Between 1983 and 1988, 402 women with ages ranging from 18 to 73 years were treated for cervical intraepithelial neoplasia using the CO{sub 2}-laser. 89 patients underwent vaporization and 313 conization. Preoperative biopsy examination showed CIN III in 214 patients. Five cases of invasive cancer were diagnosed, either preoperatively after conization or on both occasions. At the first postoperative examination residual disease was found in 21 patients of the vaporization group and in 13 patients of the conization group. Later examinations revealed recurrence in 10 patients in the vaporization group and in 13 patients in the conization group. Median time for recurrence was 11 months. 30 patients were treated twice or more. No case of invasive cancer was diagnosed after treatment. 18 refs., 6 tabs.

A Study on Cervical Cancer Screening Using Pap Smear Test and Clinical Correlation

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Pushp Lata Sachan

2018-01-01

Full Text Available Objective: The objective of the study is to evaluate the use of the Pap smear screening method for detection of precancerous lesions. Methods: All women who visited the outpatient gynecology clinic of the Department of Obstetrics and Gynaecology at King Georges Medical University, Lucknow, UP, India, over 1 year for different clinical problems were recruited for the study. A total of 1650 women who were sexually active and over 21 years of age were enrolled in the study. A clinical examination, an examination per speculum, and a vaginal examination were performed and a history taken for all women. A Pap smear was used for all women to screen for cervical cancer. The smear was obtained using an Ayre spatula and spread over a marked glass slide, which was placed in 95% ethyl alcohol and sent to the Department of Pathology for cytopathological examination. All data were recorded using a predetermined pro forma. Women who had visible malignant cervical lesions were excluded from the study. Results: Most women were in the age range of 30–50 years and multiparous. Vaginal discharge was the most common complaint, occurring in 36.96% of the women. An irregular menstrual cycle was the complaint of 12.78% and abdominal pain of 25.63% of women, while 15.15% were asymptomatic. The Pap smear test of 93.57% of the women was adequately taken, while 6.42% of the individuals had an inadequate sample. The test was negative for malignancy in 48.84%, and 42.66% had infection or inflammation. Atypical squamous cells of undetermined significance (ASCUS, low-grade squamous intraepithelial lesion (LSIL, and high-grade squamous intraepithelial lesion (HSIL were detected in 2.90%, 5.09%, and 0.48%, respectively. Women with Pap tests positive for ASCUS, LSIL, and HSIL underwent a colposcopy and guided biopsy. Conclusions: Women with an abnormal Pap test should undergo a colposcopy, and those with abnormal colposcopy findings should be advised to undergo a biopsy. A Pap

TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

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Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

2016-06-01

Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

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

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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.

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

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d'Assuncao, Jefferson; Irwig, Les; Macaskill, Petra; Chan, Siew F; Richards, Adele; Farnsworth, Annabelle

2007-01-01

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; Pcytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were satisfactory for examination and more contained low grade cytological

Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ▿

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Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-01-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases. PMID:20089764

Concordance analysis of methylation biomarkers detection in self-collected and physician-collected samples in cervical neoplasm

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Chang, Cheng-Chang; Huang, Rui-Lan; Liao, Yu-Ping; Su, Po-Hsuan; Hsu, Yaw-Wen; Wang, Hui-Chen; Tien, Chau-Yang; Yu, Mu-Hsien; Lin, Ya-Wen; Lai, Hung-Cheng

2015-01-01

Non-attendance at gynecological clinics is a major limitation of cervical cancer screening and self-collection of samples may improve this situation. Although HPV testing of self-collected vaginal samples is acceptable, the specificity is inadequate. The current focus is increasing self-collection of vaginal samples to minimize clinic visits. In this study, we analyzed the concordance and clinical performance of DNA methylation biomarker (PAX1, SOX1, and ZNF582) detection in self-collected vaginal samples and physician-collected cervical samples for the identification of cervical neoplasm. We enrolled 136 cases with paired methylation data identified from abnormal Pap smears (n = 126) and normal controls (n = 10) regardless of HPV status at gynecological clinics. The study group comprised 37 cervical intraepithelial neoplasm I (CIN1), 23 cervical intraepithelial neoplasm II (CIN2), 16 cervical intraepithelial neoplasm III (CIN3), 30 carcinoma in situ (CIS), 13 squamous cell carcinomas (SCCs) and seven adenocarcinomas (ACs)/adenosquamous carcinomas (ASCs). PAX1, SOX1 and ZNF582 methylation in study samples was assessed by real-time quantitative methylation-specific polymerase chain reaction analysis. We generated methylation index cutoff values for the detection of CIN3+ in physician-collected cervical samples for analysis of the self-collected group. Concordance between the physician-collected and self-collected groups was evaluated by Cohen’s Kappa. Sensitivity, specificity and area under curve (AUC) were calculated for detection of CIN3+ lesions. Finally, we produced an optimal cutoff value with the best sensitivity from the self-collected groups. We generated a methylation index cutoff value from physician-collected samples for detection of CIN3+. There were no significant differences in sensitivity, specificity of PAX1, SOX1 and ZNF582 between the self-collected and physician-collected groups. The methylation status of all three genes in the normal control

High-risk human papilloma virus management in pregnancy with cervical intraepithelial neoplasia during pregnancy and postpartum in China.

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He, Yue; Wu, Yu-Mei; Zhao, Qun; Wang, Tong; Song, Fang; Zhu, Li

2014-02-01

To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and postpartum in China. In this prospective case-control study, 168 pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect HR-HPV DNA load amounts and the tests were completed in 3-6 months after childbirth. During pregnancy: as the CIN grade increased, the HR-HPV infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000), while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher than that of other grades. During pregnancy and 3-6 months postpartum : the amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6 months postpartum with the same grade of CIN. The findings emphasize the importance of undergoing the HCII test 3-6 months postpartum. It should be noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after childbirth. Further treatments of pregnancy with CIN should be considered according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months after birth, but not according to the persistence of HR-HPV during pregnancy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

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Oga, Emmanuel A; Brown, Jessica P; Brown, Clayton; Dareng, Eileen; Adekanmbi, Victor; Odutola, Michael; Olaniyan, Olayinka; Offiong, Richard; Obende, Kayode; Adewole, Ayodele Stephen; Peter, Achara; Dakum, Patrick; Adebamowo, Clement

2016-05-11

The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.

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.

Cervical cytological changes in HIV-infected patients attending care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania

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Mwakigonja Amos R

2012-02-01

Full Text Available Abstract Background Tanzania is among Sub-Saharan countries mostly affected by the HIV and AIDS pandemic, females being more vulnerable than males. HIV infected women appear to have a higher rate of persistent infection by high risk types of human papillomavirus (HPV strongly associated with high-grade squamous intraepithelial lesions (HSIL and invasive cervical carcinoma. Furthermore, although HIV infection and cervical cancer are major public health problems, the frequency and HIV/HPV association of cervical cancer and HSIL is not well documented in Tanzania, thus limiting the development of preventive and therapeutic strategies. Methods A prospective unmatched, case-control study of HIV-seropositive, ≥ 18 years of age and consenting non-pregnant patients attending the care and treatment center (CTC at Muhimbili National Hoospital (MNH as cases was done between 2005 and 2006. HIV seronegative, non-pregnant and consenting women recruited from the Cervical Cancer Screening unit (CCSU at ORCI were used as controls while those who did not consent to study participation and/or individuals under Results A total of 170 participants from the two centers were recruited including 50 HIV-seronegative controls were from the CCSU. Ages ranged from 20-66 years (mean 40.5 years for cases and 20-69 years (mean 41.6 years for controls. The age group 36-45 years was the most affected by HIV (39.2%, n = 47. Cervicitis, squamous intraepithelial lesions (SIL and carcinoma constituted 28.3% (n = 34, 38.3% (n = 46 and 5.8% (n = 7 respectively among cases, and 28% (n = 14, 34% (n = 17 and 2% (n = 1 for controls, although this was not statistically significant (P-value = 0.61. IHC showed that p53 was not detectable in HPV + Pap smears and cell blocks indicating possible degradation. Conclusions The frequency of SIL and carcinoma appeared to be higher among HIV-infected women on HAART compared to seronegative controls and as expected increased with age. HIV

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

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Taxa, Luis; Jeronimo, Jose; Alonzo, Todd A; Gage, Julia; Castle, Philip E; Cremer, Miriam L; Felix, Juan C

2018-01-01

To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting. One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically. The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth. Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.

Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

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Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

2017-03-15

To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa.

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Smith, Jennifer S; Sanusi, Busola; Swarts, Avril; Faesen, Mark; Levin, Simon; Goeieman, Bridgette; Ramotshela, Sibongile; Rakhombe, Ntombiyenkosi; Williamson, Anna L; Michelow, Pam; Omar, Tanvier; Hudgens, Michael G; Firnhaber, Cynthia

2017-08-01

Mortality associated with cervical cancer is a public health concern for women, particularly in HIV-seropositive women in resource-limited countries. HIV-seropositive women are at a higher risk of high-grade cervical precancer, which can eventually progress to invasive carcinoma as compared to HIV-seronegative women. It is imperative to identify effective treatment methods for high-grade cervical precursors among HIV-seropositive women. Randomized controlled trial data are needed comparing cryotherapy vs loop electrosurgical excision procedure treatment efficacy in HIV-seropositive women. Our primary aim was to compare the difference in the efficacy of loop electrosurgical excision procedure vs cryotherapy for the treatment of high-grade cervical intraepithelial neoplasia (grade ≥2) among HIV-seropositive women by conducting a randomized clinical trial. HIV-seropositive women (n = 166) aged 18-65 years with histology-proven cervical intraepithelial neoplasia grade ≥2 were randomized (1:1) to cryotherapy or loop electrosurgical excision procedure treatment at a government hospital in Johannesburg. Treatment efficacy was compared using 6- and 12-month cumulative incidence posttreatment of: (1) cervical intraepithelial neoplasia grade ≥2; (2) secondary endpoints of histologic cervical intraepithelial neoplasia grade ≥3 and grade ≥1; and (3) high-grade and low-grade cervical cytology. The study was registered (ClinicalTrials.govNCT01723956). From January 2010 through August 2014, 166 participants were randomized (86 loop electrosurgical excision procedure; 80 cryotherapy). Cumulative cervical intraepithelial neoplasia grade ≥2 incidence was higher for cryotherapy (24.3%; 95% confidence interval, 16.1-35.8) than loop electrosurgical excision procedure at 6 months (10.8%; 95% confidence interval, 5.7-19.8) (P = .02), although by 12 months, the difference was not significant (27.2%; 95% confidence interval, 18.5-38.9 vs 18.5%; 95% confidence interval, 11

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

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

2016-01-01

Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression. © 2015 Royal College of Obstetricians and Gynaecologists.

IFNG polymorphism (+874 T>A is not a risk factor for cervical cancer

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Ani Melani Maskoen

2013-04-01

Full Text Available Introduction Cervical cancer cases are rising and many women are infected with human papillomavirus (HPV. Interferon gamma (IFN-ã is one of the key regulatory cytokines that influence the HPV clearance. The production and the function of IFN-ã may impaired by the defect of the IFNG gene leading to the cervical malignant progression. This study aimed to examine the association between IFNG+874 T>A polymorphism and cervical cancer in women Methods In a case-control study design, consecutive untreated women with cervical cancer who showed for the first time in Hasan Sadikin Hospital Bandung were enrolled (n=98 and for controls women who came for PAP smear (n = 81. Controls were not matched in ages and ethnicities. DNA extracted from blood was amplified by amplification refractory mutation system - polymerase chain reaction method (ARMS – PCR to detect IFNG+874 T>A polymorphism. Results The distribution of IFNG genotypes TT, TA and AA for women with cervical cancer who met the inclusion criteria (n= 64 and with negative intraepithelial lesion or malignancy (n=42 were 14.1%, 50.0%, 35.9% and 7.1%, 52.4%, 40.5%, respectively. No significant differences could be observed between both groups (p=0.64. Stratifying the cervical cancer women into a group of squamous cell carcinoma (n = 54 revealed no statistical different. Conclusion IFNG +874 T>A polymorphismseems not to contribute in susceptibility to cervical cancer. Identification of other variants in IFNG gene signaling and its role in the development of cervical cancer diseases need to be further examined.

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

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

2012-01-01

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

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Mr Olusoji

favouring neoplasia (AGC-FN), Atypical glandular cell of ... Screening for cervical dysplasia is critical for early detection in order to reverse this trend. ... of43.9% in low grade squamous intraepithelial lesion was recorded among the patients.

Clinical investigation of the safety and efficacy of a cervical intraepithelial neoplasia treatment using a hyperthermia device that uses heat induced by alternating magnetic fields

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Koizumi, Koji; Fujioka, Toru; Yasuoka, Toshiaki; Inoue, Aya; Uchikura, Yuka; Tanaka, Hiroki; Takagi, Katsuko; Mori, Miki; Koizumi, Masae; Hashimoto, Hisashi; Matsumoto, Takashi; Matsubara, Yuko; Matsubara, Keiichi; Nawa, Akihiro

2016-01-01

Multiple techniques have been used for the conservative treatment of high-grade cervical intraepithelial neoplasia (HG-CIN) in women of fertile age. Conization has been associated with stenosis of the cervix and a decrease in cervical mucus secretion, in addition to the increase in the risk of cervical canal shortening and problems during the perinatal period, including premature birth and premature rupture of membranes. Although the laser transpiration technique does not cause shortening of the cervical canal, it is associated with the recurrent risk of deep residual disease. The present study aimed to investigate the therapeutic safety and efficacy of the therapy performed using the transaction magnetic field induction heating device, AMTC400, in fertile patients with HG-CIN (excluding carcinoma in situ). Four premenopausal patients with CIN3 and high-risk human papilloma virus (HPV)-positive were treated using an AMTC400. Chronological colposcopic findings, high-risk HPV, final histological findings with conization and follow-up data were evaluated. All the treatments were successfully performed on the in-patients without anesthesia. Intra- and postoperative complications included minor pain and bleeding in all cases. Two of the cases (50%) were high-risk HPV-negative following the treatments. All cases exhibited a change in the observed color (to white), and subsequent epithelization following treatment. Although cytological analysis at 5 weeks following the treatment confirmed the cases were negative for intraepithelial lesions and malignancies, a definitive histology with conization 6 weeks following the treatment confirmed CIN1 and koilocytosis in all cases. The assessment of treatment effectiveness was determined as a moderate improvement in all cases. In conclusion, thermotherapy applied using AMTC400 represented a safe and effective treatment for HG-CIN in women of fertile age. However, additional improvements associated with the site of puncture needles

Should LSIL with ASC-H (LSIL-H in cervical smears be an independent category? A study on SurePath™ specimens with review of literature

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Shidham Vinod B

2007-03-01

Full Text Available Abstract Background Cervical smears exhibiting unequivocal features of 'low grade squamous intraepithelial lesion' (LSIL are occasionally also admixed with some cells suspicious for, but not diagnostic of, 'high grade squamous intraepithelial lesion' (HSIL. Only a few studies, mostly reported as abstracts, have evaluated this concurrence. In this study, we evaluate the current evidence that favors a distinct category for "LSIL, cannot exclude HSIL" (LSIL-H, and suggest a management algorithm based on combinations of current ASCCP guidelines for related interpretations. Methods We studied SurePath™ preparations of cervical specimens from various institutions during one year period. Cytohisto correlation was performed in cases with cervical biopsies submitted to our institution. The status of HPV DNA testing was also noted in some LSIL-H cases with biopsy results. Results Out of 77,979 cases 1,970 interpreted as LSIL (1,523, LSIL-H (146, 'atypical squamous cells, cannot exclude HSIL' (ASC-H (109, and HSIL (192 were selected. Concurrent biopsy results were available in 40% (Total 792 cases: 557 LSIL, 88 LSIL-H, 38 ASCH, and 109 HSIL. Biopsy results were grouped into A. negative for dysplasia (ND, B. low grade (HPV, CIN1, CIN1 with HPV, and C. high grade (CIN 2 and above. The positive predictive values for various biopsy results in relation to initial cytopathologic interpretation were: a. LSIL: (557 cases: ND 32% (179, low grade- 58% (323, high grade- 10% (55; b. LSIL-H: (88 cases: ND 24% (21, low grade- 43% (38, high grade- 33% (29; c. ASCH: (38 cases: ND 32% (12, low grade- 37% (14, high grade- 31% (12; d. HSIL (109 cases: ND 5% (6, low grade 26% (28, high grade 69% (75. The patterns of cervical biopsy results in cases reported as LSIL-H were compared with that observed in cases with LSIL, ASC-H, and HSIL. 94% (32 of 34 of LSIL-H were positive for high risk (HR HPV, 1 was negative for HR HPV but positive for low risk (LR, and 1 LSIL-H was

Human Papilloma Virus Genotype Distribution in Cervical lesions in Zanjan, Iran

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Ahmadi, Shahrzad; Goudarzi, Hossein; Jalilvand, Ahmad; Esmaeilzadeh, Abdolreza

2017-12-29

Objective: Cervical cancer is one of the most common cancers among women all over the world, and main cause is persistent infection with high risk human papillomavirus (HPV) strains. It has been reported that the distribution and prevalence of HPV types varies by geographical region, so that this is important for prevention by type-specific vaccines. The aim of current study was to determine the genotype distribution of HPV using the INNO-LiPA genotyping assay in Zanjan province, North West Iran. Methods: A total of 112 formalin-fixed paraffin embedded (FFPE) tissue samples from cases of low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were collected. The polymerase chain reaction (PCR) was used to amplify DNA for genotyping. Results: Among the 112 samples from females (ranging from 20 to 69 years, mean age 43.8 ± 10.1) tested for HPV DNA, 50 samples were positive. Based on results of genotyping, most common HPV genotypes were HPV18 (48%) followed by HPV-6 (24%), HPV73 (16%), HPV-51(8%), HPV-31(8%), HPV-16 (8%), HPV-56 (4%), HPV-44 (4%). Conclusion: While HPV infection is the major etiological factor for cervical cancer, presence was relatively low in our survey. In the positive cases, however, HPV18 was the most common in line with many other populations. The fact that types vary among different populations must clearly be taken into account in design of vaccines for our country. Creative Commons Attribution License

Utilization of human papillomavirus testing for cervical cancer prevention in a university hospital

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Rosekeila Simões Nomelini

2007-06-01

Full Text Available This study aimed to evaluate the performance and cost of using polymerase chain reaction (PCR and hybrid capture in the detection of cervical intraepithelial neoplasia (CIN in patients with cytological abnormalities (ASCUS/low-grade squamous intraepithelial lesion - LSIL, and the feasibility of implementing these methods in Brazil's Unified National Health System (SUS. Colposcopy gave a negative predictive value of 92.86% and efficiency of 87.8% for diagnosing CIN. The sensitivity of PCR and hybrid capture for detecting CIN was 83.33% and 66.67%, respectively, and the negative predictive value for diagnosing CIN2/CIN3 was 100% and 94.74%, respectively. The annual cost for 80 patients was lower when all patients with ASCUS/LSIL were referred for colposcopy than when HPV testing was performed and those with positive results were referred for colposcopy. Therefore, at present, it is financially unfeasible for the National Health System to implement HPV testing to screen patients with cytological abnormalities (ASCUS/LSIL. However, considering that large-scale use might make such methods cheaper, PCR should be the chosen method, since it is less expensive, more sensitive, and has a high negative predictive value.

Evaluation of microvascular densityby CD34 in squamous cell carcinoma of the tongue and its relationship with cervical lymph node metastasis

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Eshghyar N.

2009-03-01

Full Text Available "nBackground and Aim: Angiogenesis plays a central role for development and progression of malignant tumors.It is considered as an important factor for predicting of malignant tumor's behavior such as metastasis to lymph nodes and other clinicopathologic factors. However , it is still a controversial factor especially in oral squamous cell carcinoma.The aim of this study was to evaluate the correlation between angiogenesis and clinicopathologic parameters such as presence of metastatic cervical lymph node in the tongue squamous cell carcinoma. "nMaterials and Methods: In this cross-sectional study, 40 cases of squamous cell carcinoma of the tongue were selected from the archive of cancer institute of Tehran University of Medical Science. Sections were prepared from paraffin blocks and immunohistochemically stained with antibody against CD34. Stained vessels were counted in 4 fields ,the most vascular areas at low magnification, in each areas of intratumoral ,peritumoral and nontumoral adjacent tissue in two groups with metastatic lymphnodes (N+ and without (N-. The average counts from the four most vascular areas were recorded as the mean microvascular density (MVD. Data were analyzed by 3wayANOVA and Independent T- test with p<0.05 as the level of significance. "nResults: High mean MVD-CD34 was significantly correlate with positive cervical lymph node metastasis in intra tumoral and peritumoral areas but there was no significant correlation between mean MVD-CD34 and age, gender, and differentiation of tumor. "nConclusion: Based on the results of this study, CD34 can help us to determine the presence of cervical lymph node metastasis and may also determine the outcome of a primary squamous cell carcinoma of the tongue.

Experience in cervix intraepithelial neoplasia and the in situ carcinoma with radiosurgery

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Fajardo Tornes, Yarine; Lau Serrano, Dalgis; Perez Ramirez Fernando

2010-01-01

To expose the results from a longitudinal, prospective and descriptive study conducted in 1 437 patients diagnosed with cervical intraepithelial neoplasm (CIN) and in situ carcinoma (ISC) treated by radiosurgery in the neck pathology consultation of the 'Carlos Manuel de Cespedes' University Provincial Hospital during 2004-2009

Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical cancer tissues of Uygur women in Xinjiang

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Dan Wu

Full Text Available Abstract This study aimed to explore: 1 DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1, NK6 transcription factor related locus 1 gene (NKX6-1 and Deleted in bladder cancer 1 (DBC1 gene in cervical cancer tissues of Uygur women in Xinjiang, and 2 the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN and 48 cervical cancer tissues with polymerase chain reaction (PCR method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3 and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05. The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical

HPV type-related chromosomal profiles in high-grade cervical intraepithelial neoplasia

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Bierkens Mariska

2012-01-01

Full Text Available Abstract Background The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3] result from a persistent infection with high-risk human papillomavirus (hrHPV types and the accumulation of (epigenetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. Methods Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (≥ 5 years. Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. Results Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31 in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR Conclusions Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is

Radiation induced cell death in cervical squamous cell carcinoma. An immunohistochemical and ultrastructural study

International Nuclear Information System (INIS)

Atari, Eio; Toda, Takayoshi; Sadi, A.M.; Egawa, Haruhiko; Moromizato, Hidehiko; Mamadi, T.; Kiyuna, Masaya

1998-01-01

To study the process of cell death in cervical squamous cell carcinoma (SCC) after radiation, an ultrastructural and immunohistochemical study was performed. Paraffin-embedded tissue blocks of biopsy samples pre- and post-radiation stage III SCC (n=15) were collected. Irradiation caused varying ultrastructural changes including nuclear and cytoplasmic disorganization suggesting cell necrosis. Immunohistochemically, the pre-radiation specimens showed no positive reaction for tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-receptor (TNF-γ) or Fas. C-fos, p53 and bcl-2 showed positive reactions in only a few non-irradiated specimens. All of the irradiated specimens showed a positive reaction for TNF-α, and variable positive reactions were observed for TNF-γ, Fas, p53, c-fos and bcl-2. These results suggest that TNF-α, TNF-γ, and c-fos are responsible for radiation induced cell death in cervical SCC. (author)

Role of human papillomavirus testing and cytology in follow-up after conization

DEFF Research Database (Denmark)

Gosvig, Camilla F; Huusom, Lene D; Deltour, Isabelle

2015-01-01

intraepithelial neoplasia grade 2 or worse (CIN2+) after conization. DESIGN: Prospective cohort study. SETTING: Denmark. POPULATION: 667 women attending for conization. METHODS: Cervical specimens were collected during 2002-2006 at first visit after conization for cytological examination and Hybrid Capture 2......OBJECTIVE: Adequate follow-up of women who have undergone conization for high-grade cervical lesions is crucial in cervical cancer screening programs. We evaluated the performance of testing for high-risk human papillomavirus (HPV) types, cytology alone, and combined testing in predicting cervical...... detection of high-risk HPV. The women were passively followed until 2 years after first follow-up visit by linkage to the nationwide Pathology Data Bank. RESULTS: At first visit after conization (median time, 3.4 months), 20.4% were HPV-positive and 17.2% had atypical squamous intraepithelial lesions...

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.

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

International Nuclear Information System (INIS)

Li, Hui; Jiao, Shun; Li, Xin; Banu, Hasina; Hamal, Shreejana; Wang, Xianrong

2015-01-01

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.

Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix

NARCIS (Netherlands)

Kersemaekers, A. M.; van de Vijver, M. J.; Kenter, G. G.; Fleuren, G. J.

1999-01-01

Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies

Does the vaginal microbiota play a role in the development of cervical cancer?

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Kyrgiou, Maria; Mitra, Anita; Moscicki, Anna-Barbara

2017-01-01

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

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Xu, Dianbo; Wang, Danbo; Wang, Shuo; Tian, Ye; Long, Zaiqiu; Ren, Xuemei

2017-11-01

The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P 4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.

Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

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Santesso, Nancy; Mustafa, Reem A; Wiercioch, Wojtek; Kehar, Rohan; Gandhi, Shreyas; Chen, Yaolong; Cheung, Adrienne; Hopkins, Jessica; Khatib, Rasha; Ma, Bin; Mustafa, Ahmad A; Lloyd, Nancy; Wu, Darong; Broutet, Nathalie; Schünemann, Holger J

2016-03-01

Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated. To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3. Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used. Studies of nonpregnant women 18 years or older not previously treated for CIN were included. Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy. Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

Science.gov (United States)

Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Cahh Daemen, Toos; Postma, Maarten J

2016-12-07

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 HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Awareness, Knowledge and Attitudes Towards Cervical Cancer Amongst HIV-Positive Women Receiving Care in a Tertiary Hospital in Nigeria.

Science.gov (United States)

Adibe, Maxwell O; Aluh, Deborah O

2017-05-05

The incidence of cervical cancer (CC) in the sub-Saharan Africa region, where Nigeria is located, is amongst the highest in the world; it is estimated that 70,722 new cases of invasive cervical cancer occur annually in sub-Saharan Africa. Immunosuppression, especially due to human immunodeficiency virus (HIV) infection, is a predisposing factor for persistent infection with high-risk human papilloma virus (HR-HPV) and the development of squamous intraepithelial lesions. Four hundred and fifty women who attended the HIV clinic at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, and who consented to participate in the study were randomly selected. They were given self-administered questionnaires which sought to determine their awareness and knowledge of cervical cancer and attitudes towards cervical cancer screening and prevention. The media 23% (n = 103) was the most common source of information amongst respondents who had heard about cervical cancer. For all the women surveyed, the average percentage knowledge was 9.95%. Having attitude scores greater than or equal to the mean attitude score of 55.16% was regarded as having a positive attitude while a score lower than that was regarded as negative attitude. About 43.5% (n = 195) respondents had a positive attitude towards cervical cancer screening and prevention. Cervical cancer awareness and knowledge amongst women attending the HIV clinic in the Nnamdi Azikiwe University Teaching Hospital, Nnewi, were very poor. Their attitude towards cervical cancer screening practices and prevention was also very poor.

Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil

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S. M. B. Cavalcanti

1994-12-01

Full Text Available A hundred-sixty paraffin-embedded specimens from female cervical lesions were examined for human papillomavirus (HPV types 6, 11, 16 and 18 infections by non-isotopic in situ hybridization. The data were compared with histologic diagnosis. Eighty-eight (55 biopsies contained HPV DNA sequences. In low grade cervical intraepithelial neoplasias (CIN I, HPV infection was detected in 78.7 of the cases, the benign HPV 6 was the most prevalent type. HPV DNA was detected in 58 of CIN II and CIN III cases and in 41.8 of squamous cell carcinomas (SCC. Histologically normal women presented 20 of HPV infection. Oncogenic HPV was found in 10 of these cases, what may indicate a higher risk of developing CINs and cancer. Twenty-five percent of the infected tissues contained mixed infections. HPV 16 was the most common type infecting the cervix and its prevalence raised significantly with the severity of the lesions, pointing its role in cancer pathogenesis. White women presented twice the cervical lesions of mulatto and African origin women, although HPV infection rates were nearly the same for the three groups (approximately 50. Our results showed that HPV typing by in situ hybridization is a useful tool for distinguishing between low and high risk cervical lesions. Further studies are required to elucidate risk factors associated with HPV infection and progression to malignancy in Brazilian population.

New technologies in diagnosis of preinvasive cervical lesions

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I. P. Aminodova

2015-01-01

Full Text Available Results of efficiency assessment of different diagnosis for preinvasive cervical lesions are represented in the article. During investigation the retrospective analysis of 353 patient histories of women with cervical intraepithelial neoplasia (primary and recurrent, who have been observed in Ivanovskiy regional oncological dispensary from 2002 to 2011, was performed. The accuracy rates of diagnosis of cervical intraepithelial neoplasia for one or several methods including cytological study, colposcopy and fluorescence cystoscopy were compared. Fluorescence diagnosis was performed with drug fotoditazin (LLC «VETA-GRAND», marketing authorisation №LS 001246 at dose of 1,0 mg/kg body weight. The final diagnosis was determined by results of histological study. The accuracy of cytological study accounted for 67,5–80,7%. Using colposcopy the exact diagnosis was determined in 67,9–74,4% of cases. Combination of cytological study with colposcopy improved the accuracy of diagnosis up to 82.1–88.9%. The superior results were for concurrent use of cytological study with colposcopy and fluorescence diagnosis – in such case the diagnosis was correct in 92,0–96,7% of patients. The analysis of results showed that using all methods of diagnosis the accuracy of diagnosis for recurrent cervical intraepithelial neoplasia was lower than for primary lesions. The decrease of diagnosis accuracy is probably related to previous diagnosis and therapeutic manipulations on cervix. Thus, multimodal diagnosis investigation with methods of fluorescence spectroscopy allows to improve accuracy of diagnosis for preinvasive cervical lesions. 

Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

Science.gov (United States)

Chuerduangphui, Jureeporn; Pientong, Chamsai; Swangphon, Piyawut; Luanratanakorn, Sanguanchoke; Sangkomkamhang, Ussanee; Tungsiriwattana, Thumwadee; Kleebkaow, Pilaiwan; Burassakarn, Ati; Ekalaksananan, Tipaya

2018-05-09

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16 INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16 INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16 INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16 INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16 INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16 INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

Number of fragments, margin status and thermal artifacts of conized specimens from LLETZ surgery to treat cervical intraepithelial neoplasia.

Science.gov (United States)

Bittencourt, Dulcimary Dias; Zanine, Rita Maira; Sebastião, Ana Martins; Taha, Nabiha Saadi; Speck, Neila Góis; Ribalta, Julisa Chamorro Lascasas

2012-01-01

Large loop excision of the transformation zone (LLETZ) is a nontraumatic cut and coagulation method with several advantages, but it induces thermal artifacts in the cut region. The aim here was to assess the correlations of age, number of fragments, lesion grade and degree of thermal artifacts with margin quality in conized specimens from LLETZ for cervical intraepithelial neoplasia (CIN). Cross-sectional study at Universidade Federal de São Paulo (Unifesp). The records and histopathology findings of 118 women who underwent LLETZ between 1999 and 2007 were reviewed. Age, number of fragments, lesion grade, degree of thermal artifacts and margin quality were assessed. The patients' mean age was 27.14 years; 63.6% had been diagnosed with CIN II and 36.4% with CIN III. The lesion was removed as a single fragment in 79.6% of the cases. The margins were free from intraepithelial neoplasia in 85.6% and compromised in the endocervical margin in 6.8%. Fragment damage due to artifacts occurred in 2.5%. Severe artifacts occurred in 22.8%. Women aged 30 years or over presented more cases of CIN III (P < 0.0004). Neoplastic compromising of surgical margins and severe artifacts occurred more often in cases in which two or more fragments were removed, and in patients aged 30 years or over. CIN III in women aged 30 or over, when removed in two or more fragments during LLETZ, presented a greater number of compromised margins and greater severity of thermal artifacts.

Conization, frozen section examination, and planned hysterectomy in the treatment of high-grade cervical intraepithelial neoplasia Conização, exame de congelação e histerectomia planejada no tratamento de neoplasia intra-epitelial de alto grau

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Jesus Paula Carvalho

2001-12-01

Full Text Available PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64% had positive cone margins and 9 (36% had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%. Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.OBJETIVOS: Foi avaliado o papel do exame intra-operatório de congelação no diagnóstico de invasão e no estado das margens cirúrgicas em pacientes com neoplasia intra-epitelial de alto grau. CASUÍSTICA E MÉTODO: Vinte e cinco pacientes com neoplasia intra-epitelial de alto grau foram submetidas a conização cervical seguida de histerectomia. O resultado do exame

Podoplanin and SOX2 Expression in CIN 3-like Squamous Cell Carcinoma of the Cervix.

Science.gov (United States)

Stewart, Colin J R; Crook, Maxine L

2018-01-01

Squamous cell carcinoma (SCC) of the uterine cervix occasionally demonstrates a deceptive growth pattern that mimics endocervical crypt involvement by cervical intraepithelial neoplasia, grade 3 (CIN 3). Such CIN 3-like SCCs may be misinterpreted as noninvasive or minimally invasive leading to delays in diagnosis. Little is known of the factors that influence the growth patterns of cervical SCC but we suggested recently that CIN 3-like tumors might demonstrate "collective cellular invasion," which is characterized by a retained epithelial phenotype. This contrasts with the more overtly infiltrative growth of conventional SCC, which exhibits features suggestive of epithelial-mesenchymal transition. In the current study we investigated podoplanin (PP) and SOX2 expression in normal squamous epithelium, in CIN 3 and in 16 CIN 3-like SCCs 11 of which also showed a conventional invasive component. Compared with normal epithelium, CIN 3 often showed a focal loss of basal PP staining and most cases showed increased, typically diffuse, SOX2 expression. Although the immunohistochemical findings were not uniform, they generally supported collective cellular invasion in CIN 3-like tumor areas as these were often PP positive and showed diffuse SOX2 expression. In contrast, most conventional SCCs showed only focal SOX2 staining and they were typically negative, or only focally positive, for PP. The staining patterns did not reliably distinguish CIN 3 from CIN 3-like SCC. Small infiltrative tumor nests around the margins of CIN 3 or deeply invasive CIN 3-like SCC often showed a localized reduction in SOX2 expression suggesting SOX2 downregulation during the transition to invasive growth.

Which Patients With Cervical Squamous Cell Carcinoma Might Benefit From Neoadjuvant Chemotherapy?

Science.gov (United States)

Mahmoud, Omar; Einstein, Mark H

2018-06-01

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 55-year-old postmenopausal woman, gravida 5 para 5, with past medical history significant for hypertension, presented to the emergency department with profuse vaginal bleeding and a hemoglobin level of 9 g/dL. The biopsy from an irregular 6-cm cervical mass was consistent with moderately differentiated cervical squamous cell carcinoma. The physical examination did not reveal vaginal or parametrial extension of the tumor. Pelvic magnetic resonance imaging disclosed the known carcinoma, as well as a 9.2 × 7.7 × 6.7 cm anterior uterine fibroid (Fig 1). A staging positron emission tomography scan was negative for metastatic disease. After blood transfusion and vaginal packing, the patient was referred to discuss the immediate management of her newly diagnosed bleeding bulky cervical cancer. In the absence of parametrial or vaginal extension and in the absence of lymph node metastasis (both on clinical examination and imaging), she was classified as having International Federation of Gynecology and Obstetrics stage IB2 disease.

Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

Science.gov (United States)

Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2015-06-01

The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

Isolation of a novel human papillomavirus (type 51) from a cervical condyloma

International Nuclear Information System (INIS)

Nuovo, G.J.; Crum, C.P.; Levine, R.U.; Silverstein, S.J.; De Villiers, E.M.

1988-01-01

The authors cloned the DNA from a novel human papillomavirus (HPV) present in a cervical condyloma. When DNA from this isolate was hybridized at high stringency with HPV types 1 through 50 (HPV-1 through HPV-50), it showed weak homology with HPV-6 and -16 and stronger homology with HPV-26. A detailed restriction endonuclease map was prepared which showed marked differences from the maps for other HPVs that have been isolated from the female genital tract. Reassociation kinetic analysis revealed that HPV-26 and this new isolate were less than 10% homologous; hence, the new isolate is a noel strain of HPV. The approximate positions of the open reading frames of the new strain were surmised by hybridization with probes derived from individual open reading frames of HPV-16. In an analysis of 175 genital biopsies from patients with abnormal Papanicolaou smears, sequences hybridizing under highly stringent conditions to probes from this novel HPV type were found in 4.2, 6.1, and 2.4% of biopsies containing normal squamous epithelium, condylomata, and intraepithelial neoplasia, respectively. In addition, sequences homologous to probes from this novel isolate were detected in one of five cervical carcinomas examined

Prevalence and type distribution of human papillomavirus infection among women with different degrees of cervical cytological abnormalities in Sicily (Italy

Directory of Open Access Journals (Sweden)

Concetta Franchina

2016-06-01

Full Text Available Human papillomaviruses (HPVs are etiological agents of cervical cancer. In the absence of Pap smear alterations, high-risk HPV DNA can be detected in cervical samples. The prevalence of papillomavirus infection and their genotype distribution varies greatly across populations. The aims of this study were: i to assess the prevalences of HPV genotypes in people living in Eastern Sicily (Italy and the frequency of HPV multiple infections; ii to evaluate the association between HPV genotypes and cervical lesions in order to improve the epidemiological knowledge useful for monitoring or treating infected women. Nested PCR and reverse dot/blot hybridization were used for the detection and typing of HPV DNA in 315 women who had had an abnormal PAP-smear. HPV DNA test was positive in 70.5% cases; the prevalence was 50% in atypical squamous cells of undetermined significance (ASCUS, 80.8% in low grade-, and 76.2% in high grade-squamous intraepithelial lesion (H-SIL. The genotype distribution showed a predominance of HPV-16 (56.7% followed by HPV-18 (12.2%, HPV-31 (9.5% and HPV-6 (9.5%. Multiple infections were detected in 35.1% of the infected patients. High frequency of positive results for HPV was confirmed and, even in case of ASCUS, patients should be taken into account for genotyping. Our data indicate that multiple infections are consistent in women with low-grade lesions while they are less frequent in women with H-SIL. This could reinforce the theory of the multi-stage cancer model, by which one HPV type becomes predominant along with the progression of cervical lesion severity.

Cervical cancer screening in Greenland, 1997-2011

DEFF Research Database (Denmark)

Holst, Signe; Wohlfahrt, Jan; Kjær, Susanne Krüger

2016-01-01

of the screening program and to examine possible changes in cervical intraepithelial neoplasia (CIN3) incidence in Greenland during 1997-2011 according to calendar period and age. METHODS: Using nationwide registries, we calculated age-standardized incidence rates for all women born and living in Greenland......OBJECTIVE: In spite of the high incidence of cervical cancer in Greenland, no assessment has been made of the impact of organized cervical screening, introduced in 1998, in relation to occurrence of high-grade cervical lesions. The objectives of the present study were to estimate coverage...

El Sistema Bethesda 2001 The 2001 Bethesda System

Directory of Open Access Journals (Sweden)

Christine Bergeron

2003-01-01

Full Text Available The Bethesda system is a system of terminology for reporting the results of cervical cytology. It was developed in 1988, and is now widely used in the United States. This system was updated in April 2001. The most important modifications are the following: a elimination of the category "satisfactory but limited by", b the reintegration of benign modifications in the normal category, c "atypical squamous cells of undetermined significance" is now named "atypical squamous cells" and subdivided into "atypical squamous cells of undetermined significance" and "cannot exclude high grade squamous intraepithelial lesion"; and d endocervical adenocarcinoma in situ which is now a separate entity. Low grade squamous intraepithelial lesions and high grade squamous intraepithelial cells remain unchanged. Recommendations have been proposed concerning automated review and ancillary testing.El Sistema Bethesda es un sistema de terminología para informar los resultados de citología cervical. Se inició en 1988 y en la actualidad se usa en todos los Estados Unidos de América. Este sistema se actualizó en abril de 2001. Las modificaciones más importantes son las siguientes: a eliminación de la categoría "satisfactorio pero limitado por", b se reintegraron las modificaciones benignas en la categoría normal, c la categoría "células escamosas atípicas de significado indeterminado" ahora se denomina "células escamosas atípicas", y se subdivide en "células escamosas atípicas de significado indeterminado" y "no se puede excluir una lesión escamosa de alto grado", y d adenocarcinoma endocervical in situ, que ahora es una entidad separada. Las lesiones escamosas intraepiteliales de bajo y alto grado quedan sin cambios. Se proponen recomendaciones relacionadas con el uso de la revisión automatizada y la utilización de pruebas auxiliares.

Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

Science.gov (United States)

Annunziata, Clorinda; Pezzuto, Francesca; Greggi, Stefano; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

2018-03-31

Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124G > A or -146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. © 2018 UICC.

Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests

DEFF Research Database (Denmark)

Rebolj, Matejka; Bonde, Jesper; Njor, Sisse Helle

2011-01-01

To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard = 1 relative light units/cut-off level (rlu/co).......To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard = 1 relative light units/cut-off level (rlu/co)....

The expression of podoplanin protein is a diagnostic marker to distinguish the early infiltration of esophageal squamous cell carcinoma.

Science.gov (United States)

Chen, Guangyong; Xu, Rui; Yue, Bing; Mei, Xue; Li, Peng; Zhou, Xiaoge; Huang, Shoufang; Gong, Liping; Zhang, Shutian

2017-03-21

The esophageal squamous cell carcinoma (ESCC) is usually develped from low-grade intraepithelial neoplasia (LGIEN) and high-grade intraepithelial neoplasia (HGIEN) to infiltrative squamous cell carcinoma. Till now, it remains hard to screen for infiltration at earlier stages, especially the differentiation between HGEIN and early infiltrative carcinoma. The purpose of this study is to determine a role of podoplanin in differentiating between HGEIN and early infiltrative squamous cell carcinoma. Totally 133 patients pathologically diagnosed with early ESCC and/or precancerous lesions were enrolled.The EnVision two-step IHC staining technique was applied using the monoclonal mouse anti-human Podoplanin antibody (clone number: D2-40). The expressions of PDPN protein on the basal layer of squamous epithelium lesions could be divided into three different patterns: complete type, incomplete (non-continuous) type, or missing type. A diagnosis of HGEIN can be made if the basal layer showed non-continuous or complete expression of PDPN and a diagnosis of early infiltration can be made if the expression of PDPN is completely missing. Our study confirmed that PDPN was a potential biomarker to identify the presence of early infiltrative squamous cell carcinoma.

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark

DEFF Research Database (Denmark)

Thorsteinsson, Kristina; Ladelund, Steen; Jensen-Fangel, Søren

2014-01-01

and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN......INTRODUCTION: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). WLWH in Denmark attend the National ICC screening program less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH...... with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, incidences were comparable between WLWH and controls adherent to the National ICC screening program. CONCLUSIONS: Overall, WLWH develop more cervical disease than controls. However, incidences of CIN are comparable...

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark

DEFF Research Database (Denmark)

Thorsteinsson, K; Ladelund, Steen; Jensen-Fangel, S

2016-01-01

, which contains nationwide records of all pathology specimens. The cumulative incidence and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology result to first CIN/ICC were estimated. Sensitivity analyses were......OBJECTIVES: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). A recent publication found that WLWH in Denmark attend the national ICC screening programme less often than women in the general population. We aimed to estimate the incidence of cervical...... in both groups were adherent to the national ICC screening programme and had a normal baseline cytology, incidences of CIN and ICC were comparable. CONCLUSIONS: Overall, WLWH developed more cervical disease than controls. Yet, in WLWH and controls adherent to the national ICC screening programme...

Human papillomavirus testing and genotyping in cervical screening

DEFF Research Database (Denmark)

Rebolj, Matejka; Lynge, Elsebeth; Bonde, Jesper

2011-01-01

the incidence of cervical cancer, but has a low sensitivity for high-grade cervical intraepithelial neoplasia (CIN) and requires frequent testing. Several HPV tests have become available commercially. They appear to be more sensitive for high-grade CIN, and may further reduce the incidence of cervical cancer......Mass vaccination against human papillomavirus (HPV) genotypes 16 and 18 will, in the long term, reduce the incidence of cervical cancer, but screening will remain an important cancer control measure in both vaccinated and unvaccinated women. Since the 1960s, cytology screening has helped to reduce...

[Categorization of uterine cervix tumors : What's new in the 2014 WHO classification].

Science.gov (United States)

Lax, S F; Horn, L-C; Löning, T

2016-11-01

In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type. Mucinous carcinomas show marked intra- and extracellular mucin production. Almost all squamous cell carcinomas, the vast majority of adenocarcinomas, and many rare carcinoma types are HPV related. For low grade endocervical adenocarcinomas, the pattern-based classification according to Silva should be reported. Neuroendocrine tumors are rare and are classified into low-grade and high-grade, whereby the term carcinoid is still used.

[Algorithm for the differential diagnosis of precancerous and regenerative changes in the cervix uteri].

Science.gov (United States)

Sazonova, V Iu; Fedorova, V E; Danilova, N V

2013-01-01

Pretumoral changes in the epithelium of the cervix uteri include cervical intraepithelial neoplasia (CIN). CIN III should be differentiated with regenerative changes during epidermization of endocervicoses. Epidermization is proliferation of undifferentiated reserve cells that differentiate towards the squamous epithelium, by superseding the ectopic endocervical glandular epithelium. This process was called immature squamous metaplasia (ISM). The objective of the investigation was to define the significance of different morphological signs in the differential diagnosis of CIN III and ISM. One hundred and twelve cervical, CIN III, and immature squamous metaplasia biopsies were selected for examination. The selected cervical specimens were divided into 2 groups according to the presence or absence of p16 and CK17 expression. The p16+, CK17- cases were taken as true CIN III and the pl 6-, CK17+ as a regenerative process. The basis for this investigation is the signs included by O.K. Khmelnitsky into an algorithm for the differential diagnosis of epidermizing pseudoerosion and intraepithelial cancer of the cervix uteri. The algorithm was reconsidered to objectify. The investigation established great differences in the number of significant mitoses in the study groups. A clear trend was found for differences in the number of acanthotic strands. A new differential diagnostic algorithm for CIN III and ISM, which included the number of significant mitoses and acanthotic strands and p16 and CK17 expression, was proposed.

Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease

NARCIS (Netherlands)

Zoodsma, M; Nolte, IM; Schipper, M; Oosterom, E; Van der Steege, G; De Vries, EGE; Te Meerman, GJ; Van der Zee, AGJ

2005-01-01

Infection with oncogenic types of human papillomavirus (HPV) is the main causal factor of cervical cancer and its precursor lesion (cervical intraepithelial neoplasia [CIN]). Cellular immunity may be critical in the elimination of HPV-harboring cells. Interleukin-10, a T-helper type 2 cytokine, has

Atypical squamous cells of undetermined significance in patients with HPV positive DNA testing and correlation with disease progression by age group: an institutional experience.

Science.gov (United States)

Rodriguez, Erika F; Reynolds, Jordan P; Jenkins, Sarah M; Winter, Stephanie M; Henry, Michael R; Nassar, Aziza

2012-01-01

Atypical squamous cells of undetermined significance (ASC-US) is a broad diagnostic category that could be attributed to human papillomavirus infection (HPV), malignant neoplasia and reactive conditions. We evaluated our institutional experience with ASC-US in women who are positive for high risk HPV (HRHPV+) by the Digene hybrid capture method from 2005-2009 to identify the risk of progression to squamous intraepithelial lesion (SIL) and cervical intraepithelial neoplasia (CIN) in association with age. We reviewed cytologic and follow-up surgical pathology reports for all specimens available. Progression was defined as a diagnosis of at least CINI on follow-up biopsy or resection or SIL on cytology. We identified 2613 cases and follow-up was available in 1839 (70.4%). Of these 74.2% had just one follow-up, 16.2% had a total of 2 follow-ups, 5.3% had a total of 3 follow-ups, and the remaining had as many as 6 follow-ups. Among the 1839 patients, 69.4% were age 30 or younger, 16.0% were between 31 to 40, 9.0% were between 41 to 50, and 5.6% were 51 or older. Among these, 25-30% progressed to dysplasia. The risk of progression varied by age (p=0.04) and was lowest among women between the ages of 41-50. Our findings highlight the importance of continued cytologic follow-up in women with HRHPV+ ASC-US in order to detect progression of disease, although the risk of progression is age dependent.

Human Papillomavirus types distribution among women with ...

African Journals Online (AJOL)

Introduction: cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim: to determine the ...

Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies

DEFF Research Database (Denmark)

Kjær, Susanne Krüger

2009-01-01

of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks......High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number...... for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend or =6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2...

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

Science.gov (United States)

Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

Epidemiology of Cervical Squamous Intraepithelial Lesions in HIV ...

African Journals Online (AJOL)

AJRH Managing Editor

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

Plasma proteome analysis of cervical intraepithelial neoplasia and ...

Indian Academy of Sciences (India)

Prakash

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

Drug addiction is not an independent risk factor for oncogenic human papillomavirus infections or high-grade cervical intraepithelial neoplasia: case-control study nested within the Latin American Screening study cohort.

Science.gov (United States)

Syrjänen, K; Naud, P; Derchain, S; Roteli-Martins, C; Longatto-Filho, A; Tatti, S; Branca, M; Erzen, M; Hammes, L S; Matos, J; Gontijo, R; Sarian, L; Bragança, J; Arlindo, F C; Maeda, M Y S; Lörincz, A; Dores, G B; Costa, S; Syrjänen, S

2008-04-01

Drug abuse (addiction) has been listed among the risk factors for human papillomavirus (HPV) infections, but no case-control studies exist to rule out sexual behaviour and other potential confounders. The aim of this study is to evaluate the role of drug addiction as an independent predictor of HR-HPV infections and (cervical intraepithelial neoplasia) CIN2+ in an age-matched case-control (1:4) study nested within the prospective Latin American Screening (LAMS) study cohort. All 109 women in the LAMS cohort (n=12,114) reporting drug abuse/addiction were matched with four controls (n = 436) of non-abusers strictly by age. Conditional logistic regression analysis was used to estimate the co-variates of drug abuse, and the whole series (n=545) was analysed for predictors of HR-HPV and CIN2+ using univariate and multivariate regression models. Oncogenic HPV infections were significantly (P=0.019) more prevalent among abusers (37.7%) than in controls (21.9%), but there was no difference in high-grade squamous intraepithelial lesions (P=0.180) or CIN2+ lesions (P=0.201). In multivariate conditional logistic regression, number of lifetime sexual partners (P=0.0001), ever smokers (P=0.0001), non-use of OCs (P=0.013), ever having sexually transmitted diseases (STD) (P=0.041) and no previous Pap smear (P=0.027) were independent co-variates of drug addiction. Drug abuse was not an independent risk factor of high-risk (HR)-HPV infection, which was significantly predicted by (1) age below 30 years (P=0.045), (2) more than five lifetime sexual partners (P=0.046) and (3) being current smoker (P=0.0001). In multivariate model, only HR-HPV infection was an independent risk factor of CIN2+ (P=0.031), with adjusted OR=11.33 (95% CI 1.25-102.50). These data indicate that drug addiction is not an independent risk factor of either HR-HPV infections or CIN2+, but the increased prevalence of HR-HPV infections is explained by the high-risk sexual behaviour and smoking habits of these women.

[Verification of doubtful PAP smear results of women included in the screening program in the Podlaskie province].

Science.gov (United States)

Błońska, Ewa; Knapp, Piotr Andrzej

2013-08-01

Verification of uncertain PAP-smear results in a group of women covered by the cervical screening program in the Podlaski province. The main aim of the study was to identify CIN (Cervical Intraepithelial Neoplasia) lesions present, with varying degrees of severity in women with cytological diagnosis of ASCUS (atypical squamous cells of undetermined significance), LSIL (low grade squamous intraepithelial lesion), and ASC-H (atypical squamous cells - cannot exclude high grade squamous intraepithelial lesion). The study evaluated 101 cervical smears taken from the vaginal part of the cervix in a group of screened women in the Podlaski province. Cytological evaluation was performed according the Bethesda System. We analyzed abnormal smears selected from a total of 7296 cytological examinations performed during 2012 at the University Center for Pathomorphological and Genetic - Molecular Diagnosis, Medical University in Białystok. The cytological results which were of interest to us included 19 cases with ASCUS, 59 with LSIL, and 23 with ASC-H, as well as with morphological features of the presence of Human Papilloma Virus (HPV). Staining was performed using CINtecPLUS test according to the manufacturer's instructions. CINtecPLUS is a immunocytochemical test based on specially designed monoclonal antibodies (E6H4TM) that let us identify protein p16ink4a within the cervical smear Additionally the diagnostic kit was provided with antibodies for diagnosing the presence of Ki-67 protein, a known marker of cell proliferation. The result was considered positive when staining of the nucleus and the cytoplasm appeared in red and brown, respectively. All abnormal results were eventually verified by histological examination of the tissue taken from cervical lesions by diagnostic-therapeutic procedure following colposcopic evaluation of cervical lesion topography In the group of cytological smears with ASCUS, the diagnosis was positive in 5 cases (26.3%), negative in 14 (73

Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population

Directory of Open Access Journals (Sweden)

Alireza Torabi

2016-08-01

Full Text Available Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs, have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125, low grade dysplasia (cervical intraepithelial neoplasia (CIN-I, n = 4, high grade dysplasia (CIN-II and -III, n = 5 and invasive carcinoma (squamous cell carcinoma (SCC, n = 5 followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6% and pre-cancer and cancer (91.3% groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05 using Kyoto Encyclopedia of Genes and Genomes (KEGG. This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings.

Self-sampling with HPV mRNA analyses from vagina and urine compared with cervical samples.

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Asciutto, Katrin Christine; Ernstson, Avalon; Forslund, Ola; Borgfeldt, Christer

2018-04-01

In order to increase coverage in the organized cervical screening program, self-sampling with HPV analyses has been suggested. The aim was to compare human papillomavirus (HPV) mRNA detection in vaginal and urine self-collected samples with clinician-taken cervical samples and the corresponding clinician-taken histological specimens. Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 209 women with the Aptima mRNA assay (Hologic Inc, MA, USA). Cervical cytology, colposcopy, biopsy and/or the loop electrosurgical excision procedure (LEEP) were performed in every examination. The sensitivity of the HPV mRNA test in detecting high-grade squamous intraepithelial lesions (HSIL)/adenocarcinoma in situ (AIS)/cancer cases was as follows: for the vaginal self-samples 85.5% (95% CI; 75.0-92.8), the urinary samples 44.8% (95% CI; 32.6-57.4), and for routine cytology 81.7% (95% CI; 70.7-89.9). For the clinician-taken cervical HPV samples the sensitivity of the HPV mRNA test in detecting HSIL/AIS/cancer was 100.0% (95% CI; 94.9-100.0). The specificity of the HPV mRNA was similar for the clinician-taken cervical HPV samples and the self-samples: 49.0% vs. 48.1%. The urinary HPV samples had a specificity of 61.9% and cytology had a specificity of 93.3%. The sensitivity of the Aptima HPV mRNA test in detecting HSIL/AIS/cancer from vaginal self-samples was similar to that of routine cytology. The Aptima HPV mRNA vaginal self-sampling analysis may serve as a complement in screening programs. Copyright © 2018 Elsevier B.V. All rights reserved.

Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test

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Caroline Tanski Bueno

2014-09-01

Full Text Available The aim of this study was to evaluate the association between the frequency of micronuclei (MN and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001. The mean MN frequencies were 0.95 ± 1.12 (mean ± SD in the control group (n = 223, 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US (n = 50, 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN I (n = 52, 5.97 ± 1.83 in CIN II (n = 30, 7.29 ± 1.55 in CIN III (n = 17 and 8.64 ± 1.55 in invasive cancer (n = 25. These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.

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

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Oksana M. Pliten

2015-06-01

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

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH

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Jaime Gosálvez

2013-02-01

Full Text Available We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH. A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL, 10 with high-grade SIL (HG-SIL, and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH).

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Cortés-Gutiérrez, Elva I; Ortíz-Hernández, Brenda L; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime

2013-02-19

We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

Outcomes after management of young women with cervical intraepithelial neoplasia 2 with a 6-month observation protocol.

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Bleecker, Elizabeth; Koehler, Elizabeth; Smith, Jennifer; Budwit, Debra; Rahangdale, Lisa

2014-01-01

Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.

Measuring effectiveness of the cervical cancer vaccine in an Australian setting (the VACCINE study).

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Young, Elisa J; Tabrizi, Sepehr N; Brotherton, Julia Ml; Wark, John D; Pyman, Jan; Saville, Marion; Wrede, C David; Jayasinghe, Yasmin; Tan, Jeffrey; Gertig, Dorota M; Pitts, Marian; Garland, Suzanne M

2013-06-19

The quadrivalent human papillomavirus vaccine has been provided in Australia through the National Human Papillomavirus Vaccination Program since April 2007. National registry data demonstrates good coverage of the vaccine, with 73% of school-aged girls having received all three doses. To evaluate the effectiveness of the program, we propose a two-pronged approach. In one (sub study A), the prevalence of the vaccine-targeted human papillomavirus genotypes in a population cohort is being estimated, and will be analysed in relation to vaccination status, cervical cytology screening status, demographic, social, behavioural, medical and clinical factors. In sub study B, the distribution of human papillomavirus genotypes detected in high grade cervical intraepithelial neoplastic lesions from vaccine eligible women is being assessed. Sub Study A involves the recruitment of 1569 women aged 18-25, residing in Victoria, Australia, through Facebook advertising. Women who are sexually active are being asked to provide a self-collected vaginal swab, collected at home and posted into the study centre, where human papillomavirus DNA detection and genotyping is performed. Participants also complete an online questionnaire regarding sexual history, experience with, knowledge of, and attitudes towards human papillomavirus, the human papillomavirus vaccine, and cervical screening.Sub Study B will involve the collection of 500 cervical biopsies, positively identified as containing high grade cervical intraepithelial neoplastic lesions and/or adenocarcinoma in situ. Five serial sections are being taken from each case: sections 1 and 5 are being assessed to confirm the presence of the high grade cervical intraepithelial neoplastic lesions or adenocarcinoma in situ; human papillomavirus genotyping is performed on sections 2 and 3; single lesions are excised from section 4 using laser capture microdissection to specifically define causality of a human papillomavirus genotyping of each

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

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DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL  CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions

Clinicopathological importance of Papanicolaou smears for the diagnosis of premalignant and malignant lesions of the cervix.

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Bukhari, Mulazim Hussain; Saba, Kanwal; Qamar, Samina; Majeed, Muhammad Muddasar; Niazi, Shahida; Naeem, Samina

2012-01-01

Premalignant and malignant lesions are not uncommon in Pakistani women, especially in the older age-groups This study was conducted to determine the clinicopathological importance of conventional Papanicolaou (Pap) smears for the diagnosis of premalignant and malignant lesions of the cervix. Pap smears of 1000 women were examined from January 2007 to June 2009. Only cases with neoplastic cytology were included. The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the postmenopausal age-group, with the mean age being 44.7±15.63 years. The commonest clinical signs/symptoms seen among the 102 patients with neoplastic gynecological lesions were vaginal discharge and abnormal bleeding (93/102;(91.2% and 62/102;60.7%). Of the 102 cases with neoplastic lesions 46 patients (45%) had low-grade squamous cell intraepithelial lesions (LSILs), 22 (21.5%) had high-grade squamous cell intraepithelial lesions (HSILs), 14 (13.7%) had squamous cell carcinoma, and 6 (5.8%) showed features of adenocarcinoma. Ten (9.8%) cases showed cytology of atypical squamous cells of undetermined significance (ASCUS) and four (3.9%) cases had atypical glandular cells of undetermined significance (AGUS). We conclude that cervical smear examination is well suited for diagnosing neoplastic disease. It is clear that cervical neoplastic lesions are becoming a problem in Pakistan.

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

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

2017-01-01

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

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

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

2017-07-01

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

Cervical cancer screening at crossroads

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Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada

2014-01-01

Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark......, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented...... cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT...

HUMAN PAPILLOMA VIRUS IN THE ABNORMAL SQUAMOUS CELLS AND MILDY DYSKARYOTIC CELLS

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Eda Vrtačnik Bokal

2003-12-01

Full Text Available Background. A persistent infection with high-risk genotypes of human papilloma viruses (HPV represents the most important etiologic factor for the development of cervical cancer, the second most frequent cancer in women in Slovenia as well as elsewhere in the world. In the detection of precancerous lesions the cervical Papanicolaou (Pap smear screening is used in Slovenia and worldwide. Management of patients with repeat abnormal smears (Pap II represents a great and complex clinical and public health problem; repeat cytologic examinations are the routine procedure in many countries, also in Slovenia, although the sensitivity of Pap smear testing in the detection of cervical intraepithelial neoplasms (CIN II and III is relatively low. In cases of abnormal squamous cells and mildly dyskaryotic cells the presence of infections with high-risk HPV genotypes is being increasingly used as a complementary method to Pap smear testing.Methods and patients. In the study we enrolled 148 women who within two years had three subsequent Pap II smears (abnormal squamous cells or mildly dyskaryotic cells. The prevalence of HPV infections was determined using three molecular tests: Hybrid Capture II (HCII (Digene Corporation, Gaithersburg, USA and two variants of polymerase chain reaction (PCR-PGMY11/PGMY09 and PCR-CPI/CPIIG. HPV genotypes were determined using the method of enzyme restriction of PCR products multiplied by group-specific oligonucleotid primers PGMY11/PGMY09.Results. HPV infection was detected in 25.7% of women. In women aged ≤ 30 years a statistically significantly higher incidence of HPV infections was found (37.8% than in women aged ≥ 30 years (20.4%. In women aged ≤ 30 years most frequent infections, and also equally distributed, were the ones with high-risk genotypes HPV 16 and HPV 73 and with a potentially high-risk genotype HPV 26. In women aged ≥ 30 years most frequent infections, and also equally distributed, were the ones with

[Expression of gamma interferon during HPV and Chlamydia trachomatis infection in cervical samples].

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Colín-Ferreyra, María Del Carmen; Mendieta-Zerón, Hugo; Romero-Figueroa, María Del Socorro; Martínez-Madrigal, Migdania; Martínez-Pérez, Sergio; Domínguez-García, María Victoria

2015-02-01

The aim of this study was to mesure the expression of gamma interferon in HPV and Chlamydia trachomatis infection in squamous intraepithelial lesions. Samples from 100 patients diagnosed by colposcopy with or without squamous intraepithelial lesions were used in the present study. Each patient was found to be infected by HPV and C.trachomatis. Relative gamma interferon mRNA expression was assessed using a real-time reverse transcriptase PCR assay (RT-PCR). The relative units of expression of gamma interferon mRNA were 13, 1.8 and 0.3, for HPV and C.trachomatis co-infection, or HPV or C.trachomatis infection, respectively. HPV and C.trachomatis could overstimulate the expression of gamma interferon. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism

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Hu, Zheng; Zhu, Da; Wang, Wei

2015-01-01

Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis1. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and ...

Atypical squamous cells, cannot exclude high grade squamous intraepithelial (ASC-H in HIV-positive women

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Michelow Pam

2010-01-01

Full Text Available Objective: South Africa has very high rates of both HIV infection and cervical pathology. The management of ASC-H is colposcopy and directed biopsy, but with so many women diagnosed with HSIL and a dearth of colposcopy centres in South Africa, women with cytologic diagnosis of ASC-H may not be prioritized for colposcopy. The aim of this study was to determine if HIV-positive women with a cytologic diagnosis of ASC-H should undergo immediate colposcopy or whether colposcopy can be delayed, within the context of an underfunded health care setting with so many competing health needs. Materials and Methods: A computer database search was performed from the archives of an NGO-administered clinic that offers comprehensive HIV care. All women with a cytologic diagnosis of ASC-H on cervical smears from September 2005 until August 2009 were identified. Histologic follow up was sought in all patients. Results: A total of 2111 cervical smears were performed and 41 diagnosed as ASC-H (1.94%. No histologic follow up data was available in 15 cases. Follow up histologic results were as follows: three negative (11.5%, five koilocytosis and/ or CIN1 (19.2%, ten CIN2 (38.5% and eight CIN3 (30.8%. There were no cases of invasive carcinoma on follow up. Conclusion: The current appropriate management of HIV-positive women in low-resource settings with a diagnosis of ASC-H on cervical smear is colposcopy, despite the costs involved. In the future and if cost-effective in developing nations, use of novel markers may help select which HIV-positive women can be managed conservatively and which ones referred for more active treatment. More research in this regard is warranted.

Impact of visual inspection with acetic acid plus cryotherapy "see and treat" approach on the reduction of the population burden of cervical preinvasive lesions in Southeast Nigeria.

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Chigbu, C O; Onyebuchi, A K; Nnakenyi, E F; Egbuji, C C

2017-02-01

The aim of this study is to determine the impact of visual inspection with acetic acid (VIA) plus immediate cryotherapy on the prevalence of VIA-detected cervical squamous intraepithelial lesion (SIL). Women in four rural communities in Southeast Nigeria were screened with VIA. Women who tested positive to VIA were offered either immediate cryotherapy or large loop excision of the transformation zone based on predetermined eligibility criteria. Cervical biopsies were taken before cryotherapy and examined by consultant histopathologists. All participants were rescreened 1 year later. The main outcome measures were population prevalence of cervical precancers before and after intervention, cure rates, and over-treatment rates. A total of 653 women participated in the study. The prevalence of cervical SIL before the intervention was 8.9% (58/653). The prevalence 1 year later was 1.4% (9/649). This gave an 84.3% reduction in the population prevalence of SIL. The reduction in cervical SIL prevalence was statistically significant (P = 0.0001). The prevalence of high-grade SIL reduced significantly from 4.1% (27/653) preintervention to 0.5% (3/649) 1 year postintervention (P = 0.0001). This gave an 87.8% reduction in the population prevalence of high-grade SIL. Cryotherapy provided a cure rate of 87.9% (95% confidence interval: 76.82-94.33). Population cervical cancer prevention using VIA plus immediate cryotherapy leads to significant reduction in the population prevalence of cervical SIL. This has the potential of being an acceptable supplement to cervical cytology for cervical cancer prevention in low-income populations.

Real-time colorimetric detection of DNA methylation of the PAX1 gene in cervical scrapings for cervical cancer screening with thiol-labeled PCR primers and gold nanoparticles

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Huang J

2016-10-01

proposed method showed that the areas under the receiver operating characteristic curve (AUCs of PAX1 were 0.833, 0.742, and 0.739 for the detection of cervical intraepithelial neoplasms grade 2 and worse lesions (CIN2+, cervical intraepithelial neoplasms grade 3 and worse lesions (CIN3+, and squamous cell carcinoma, respectively. The sensitivity and specificity for detecting CIN2+ lesions were 0.941 and 0.600, respectively, with a cutoff value of 31.27%. The proposed method also showed superior sensitivity over qMSP methods for the detection of CIN2+ and CIN3+ (0.941 vs 0.824 and 1.000 vs 0.800, respectively. Furthermore, the novel method exhibited higher AUC (0.833 for the detection of CIN2+ than qMSP (0.807. Conclusion: The results of thiol-labeled AuNP method were clearly observed by the naked eyes without requiring any expensive equipment. Therefore, the thiol-labeled AuNP method could be a simple but efficient strategy for cervical cancer screening. Keywords: colorimetric detection, gold nanoparticles, DNA methylation, cervical cancer screening, UV-vis, high sensitivity, quantitative detection

Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

International Nuclear Information System (INIS)

He, Mian; Cheng, Yang; Li, Wen; Liu, Qiongshan; Liu, Junxiu; Huang, Jinghe; Fu, Xiaodong

2010-01-01

The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy

Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

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Huang Jinghe

2010-04-01

Full Text Available Abstract Background The elevated expression of vascular endothelial growth factor C (VEGF-C is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. Methods In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. Results On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. Conclusions These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

Clinical assessment of the response of metastatic cervical lymph nodes to radiation in patients with squamous cell carcinoma

International Nuclear Information System (INIS)

Sekiguchi, Kenji

1985-01-01

Between November 1981 to May 1985, measurements were made of the exponential regression of 69 cervical nodes from 37 patients with squamous cell carcinoma treated with radiotherapy in the division of clinical oncology, the department of Radiology at the Tokyo Women's Medical College. The volume-halving time (T 1/2(V)) which was calculated in each case was analysed. The results were as follows. 1. T 1/2(V) of oral cavity, lung, hypopharynx and esophagus seemed to be longer than those of oropharynx, uterus, larynx and epipharynx. 2. T 1/2(V) of well differentiated squamous cell carcinoma seemed to be shorter than those of moderately and poorly differentiated squamous cell carcinoma, however no significant difference was found. 3. There were two patterns of initial regression. One half of lymph nodes regressed with an initial shoulder and the other half regressed without it. And T 1/2(V) of regression curve with it was statistically shorter than that without it. 4. There was no significant correlation between T 1/2(V) and the lymph node size. 5. The response rate of lymph node to radiotherapy was higher and the regrowth rate was lower in the fast regression group, compared with those in the slow regression group. (author)

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

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Felicidad Gimenez

2011-06-01

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

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.

Cervical Screening within HIV Care: Findings from an HIV-Positive Cohort in Ukraine

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Bailey, Heather; Thorne, Claire; Semenenko, Igor; Malyuta, Ruslan; Tereschenko, Rostislav; Adeyanova, Irina; Kulakovskaya, Elena; Ostrovskaya, Lyudmila; Kvasha, Liliana; Cortina-Borja, Mario; Townsend, Claire L.

2012-01-01

Introduction HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe. Methods Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored. Results Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively). Conclusions In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV

Restriction of human papillomavirus DNA testing in primary cervical screening to women above age 30

DEFF Research Database (Denmark)

Rebolj, Matejka; Njor, Sisse H; Lynge, Elsebeth

2012-01-01

Cervical screening with human papillomavirus (HPV) testing is less specific for high-grade cervical intraepithelial neoplasia (=CIN3) than cytology. The aim of this systematic review was to determine whether a restriction of HPV testing to women aged at least 30 years would eliminate the problem...

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

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Budal, Elisabeth Berge; Haugland, Hans Kristian; Skar, Robert; Mæhle, Bjørn Ove; Bjørge, Tone; Vintermyr, Olav Karsten

2014-01-01

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005–2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followe...

Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

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Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

2015-11-01

Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

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

Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

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Hillemanns, Peter; Einstein, Mark H; Iversen, Ole Erik

2015-02-01

Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

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Gajjar, Ketan; Martin-Hirsch, Pierre P L; Bryant, Andrew; Owens, Gemma L

2016-07-18

Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral

Lymphatic mapping to tailor selective lymphadenectomy in squamous cell carcinoma of oral cavity

International Nuclear Information System (INIS)

Haq, M.E.U.; Warraich, R.A.; Abid, H.

2010-01-01

Objective: The purpose of this study was to determine the distribution of cervical lymph node metastases in the Squamous cell carcinoma of oral tongue and or floor of mouth; hence to improve the pretreatment evaluation of these patients. Study design: Descriptive study. Setting: Department of Oral and Maxillofacial Surgery, King Edward Medical University/ Mayo Hospital Lahore. From July 1, 2008 to December 31, 2009. Methods: This study was carried out on 50 consecutive patients who were having Squamous cell carcinoma of oral tongue and or floor of the mouth with T1 - T4 lesions. Results: Neck lymph node levels I and II were the most common sites of cervical lymph node metastases that was, 30%. Levels IV and V were involved very rarely. The overall metastases to cervical lymph node levels I - III combined was seen in 90% cases of oral tongue or floor of the mouth. Conclusion: The most common region for cervical lymph node metastases in Squamous Cell Carcinoma of oral tongue and floor of mouth is levels I - III in the ipsilateral neck, so based on pattern of metastases, supraomohyoid neck dissection for cN+ and functional neck dissection for cN+ necks are suggested. Key Words: Oral Squamous cell carcinoma (OSCC), cervical lymph node metastasis, cN+ (clinically lymph node negative), cN+ (clinically lymph node positive) (N1 - N/sub 3/), pN+ (pathologically lymph node metastases found), elective neck dissection, occult metastasis, radical neck dissection (RND). (author)

[Reparative and neoplastic spheroid cellular structures and their mathematical model].

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Kogan, E A; Namiot, V A; Demura, T A; Faĭzullina, N M; Sukhikh, G T

2014-01-01

Spheroid cell structures in the cell cultures have been described and are used for studying cell-cell and cell- matrix interactions. At the same time, spheroid cell structure participation in the repair and development of cancer in vivo remains unexplored. The aim of this study was to investigate the cellular composition of spherical structures and their functional significance in the repair of squamous epithelium in human papilloma virus-associated cervical pathology--chronic cervicitis and cervical intraepithelial neoplasia 1-3 degree, and also construct a mathematical model to explain the development and behavior of such spheroid cell structure.

Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

Science.gov (United States)

2018-05-23

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

Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis

OpenAIRE

Holm, Ruth; de Putte, Gregg Van; Suo, Zhenhe; Lie, A Kathrine; Kristensen, Gunnar B

2008-01-01

By using immunohistochemistry we investigated the expression of EphA2 and EphrinA-1 in 217 early squamous cell cervical carcinomas and examine their prognostic relevance. For EphA2 expression, 21 tumors (10%) showed negative, 108 (50%) weak positive, 69 (32%) moderate positive and 19 (9%) strong positive, whereas for EphrinA-1 expression, 33 tumors (15%) showed negative, 91 (42%) weak positive, 67 (31%) moderate positive and 26 (12%) strong positive. In univariate analysis high expression (st...

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

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

2012-07-01

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

Bizarre cell dysplasia of the cervix.

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Ondič, Ondrej; Ferko, Radoslav; Kašpírková, Jana; Švajdler, Marián; Rýchly, Boris; Talarčík, Peter; Bouda, Jiří; Michal, Michal

2017-02-01

The aim of this study was the characterization of a new subtype of high-grade cervical squamous intraepithelial lesion (HSIL) with enlarged cells containing bizarre nuclei: so-called bizarre cell dysplasia (BCD). A total of 29 cervical cone biopsy samples of this type of dysplasia were studied. Multi-target polymerase chain reaction and in situ hybridization human papillomavirus (HPV) detection was performed in all cases. BCD was defined as a subtype of HSIL characterized by the presence of large dysplastic cells with abnormal, large pleomorphic nuclei or multinucleation causing nucleomegaly. This results in bizarre nuclear shapes. Bizarre cells are scattered throughout the whole thickness of the dysplastic squamous epithelium. The BCD lesions arise within the conventional/classic high grade or "bland" type squamous dysplasia HSIL. Statistically they were significantly associated with HVP type 16. A significant association with other studied viruses (Herpes simplex virus [HSV]1, HSV2, Varicella zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and human polyomaviruses BK and JC) was not confirmed. BCD involves cytologically characteristic morphologic changes that are recognizable, but which may pose some risk of misdiagnosis as low-grade squamous intraepithelial lesion due to the enlargement of dysplastic cells and multinucleation. Based on the unique histological, cytological and biological features of BCD including strong association with HPV 16 infection, we believe that this is a specific, and so far unrecognized variant of HSIL. © 2017 Japan Society of Obstetrics and Gynecology.

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

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Arbyn, Marc; Buntinx, Frank; Van Ranst, Marc; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Dillner, Joakim

2004-02-18

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II

[Relationship and interaction between folate and expression of methyl-CpG-binding protein 2 in cervical cancerization].

Science.gov (United States)

Li, Q L; Ding, L; Nan, J; Liu, C L; Yang, Z K; Chen, F; Liang, Y L; Wang, J T

2016-07-01

To explore the interaction between folate and the expression of methyl-CpG-binding protein 2(MeCP2)in cervical cancerization. Forty one patients diagnosed with cervical squamous cell carcinoma(SCC), 71 patients diagnosed with cervical intraepithelial neoplasm(CIN1, n=34; CIN2 +, n=37)and 61 women with normal cervix(NC)were recruited in this study. Microbiological assay was conducted to detect the levels of serum folate and RBC folate, Western blot assay and real-time PCR were performed to detect the expression levels of MeCP2 protein and mRNA, respectively. The data were analyzed by Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation with SPSS statistical software(version 20.0), and the interaction were evaluated by using generalized multifactor dimensionality reduction(GMDR)model. The levels of serum folate(H=44.71, Pfolate(H=5.28, Pfolate level and RBC folate level(r=0.270, Pfolate level and the expression level of MeCP2 protein(serum folate: r=-0.226, P=0.003; RBC folate: r=-0.164, P=0.004). Moreover, the results by GMDR model revealed there were interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and MeCP2 mRNA high expression in SCC and CIN2 + patients. Folate deficiency and high expression of MeCP2 gene might increase the risk of cervical cancer and its precancerous lesions through interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and mRNA high expression in the progression of cervical cancerization.

Efficacy and prognostic analysis of chemoradiotherapy in patients with thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis alone

International Nuclear Information System (INIS)

Zhang, Peng; Xi, Mian; Zhao, Lei; Li, Qiao-Qiao; He, Li-Ru; Liu, Shi-Liang; Shen, Jing-Xian; Liu, Meng-Zhong

2014-01-01

The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50–68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival

Progression and regression of cervical pap test lesions in an urban AIDS clinic in the combined antiretroviral therapy era: a longitudinal, retrospective study.

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Lofgren, Sarah M; Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

2015-05-01

Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval.

Clinical significance of HPV DNA cotesting in Korean women with ASCUS or ASC-H.

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Lee, Sanghoon; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan; Kim, In Sun; Lee, Nak Woo

2014-12-01

The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid-based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15-80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low-grade squamous intraepithelial lesion (26.8%), ASC-H (7.0%), and high-grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV-negative had ≥cervical intraepithelial neoplasia (CIN2) (P age groups: ASCUS and ASC-H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV-negative women and a higher proportion of ≥CIN2 in HPV-positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV-negative women, especially in women ≥30. © 2014 Wiley Periodicals, Inc.

Screening of cervical cancer by VIA among women in Rajshahi Medical College Hospital

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N Yusuf

2012-02-01

Full Text Available Objective: To find out different grades of cervical intraepithelial lesions of cervix with visual inspection of cervix with acetic acid (VIA. Methods: VIA was carried out in 540 eligible women attending Gynaecology Outpatient Department for gynecological problems. The women underwent a complete clinical evaluation. All screened women (540 were evaluated by colposcopy and biopsies which were taken from different quadrants of the cervix. The final diagnosis was based on histology, which allowed direct estimation of sensitivity, specificity, and predictive values of VIA and colposcopy. Those with abnormal lesions diagnosed by histology were considered as true positive. Results: Out of 540 patients screened, 212 (39.27% were VIA positive. More patients with cervical lesions were detected by VIA than colposcopy. There were 63 (11.67% women with histologic cervical intraepithelial neoplasia (CIN I, which was found in 150 (27.78% by VIA and 138 (25.56% by colposcopy. VIA and colposcopy yielded high grade CIN II in the same number of patients. Biopsy proven cancer was found in 24 (4.45% which was detected in 18 (3.33% by VIA and colposcopy. Sensitivity and specificity of VIA were 68.50% and 70.45% respectively. Positive predictive value was 41.04% and negative predictive value was 90.85%. Conclusions: VIA can differentiate a normal cervix from a precancerous cervix with reasonable accuracy. The sensitivity and specificity of VIA are comparable to the other studies. So VIA may reduce the cervical intraepithelial lesions both in urban and rural areas.

Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

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Ohara, Kiyoshi; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

2006-01-01

Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day -1 ) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day -1 (median, 0.021 day -1 ) and late-assessed radioresponse from 0.009 to 0.091 day -1 (median, 0.021 day -1 ), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R 2 = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness

[Pap smear for mass screening: Results of an African experiment].

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Somé, O-R; Zongo, N; Ka, S; Wardini, R; Dem, A

2016-06-01

To assess the impact of smear test in the fight against cervix uteri cancer in Senegal. This was a descriptive cross-sectional study of 1836 Pap smears performed in patients over 15 years during several screening campaigns in Senegal conducted between June 2010 and June 2012. We analyzed epidemiological data, pathological smears, and the proposed management. In 69% of cases, the women were less than 45 years old. They were mostly multiparous and did not use contraceptive methods before. The smears were interpreted in 91.4% (n=1661) and were pathological in 5.2% of cases. They revealed mainly atypical squamous cells of undetermined significance, squamous intraepithelial low-grade lesions, and squamous intraepithelial high-grade lesions, respectively in 2.5% (n=46), 1.7% (n=30) and 1% (n=19) of cases. Multiparity, early marriages were the main risk factors. Patients with pathological smars had colposcopy with cryotherapy (23 cases), and colposcopy and biopsy (13 cases). A hysterectomy was performed in 4 cases. The pathological smear rate found in this study confirms the interest to continue cervical cancer screening with this practice. Strengthening of its geographical and financial access through a national prevention program will effectively help to lower cases of cervical cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

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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.

Human papillomavirus types distribution in eastern Sicilian females with cervical lesions. A correlation with colposcopic and histological findings.

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Le Donne, Maria; Giuffrè, Giuseppe; Caruso, Carmela; Nicotina, Piero Antonio; Alibrandi, Angela; Scalisi, Rosalba; Simone, Angela; Chiofalo, Benito; Triolo, Onofrio

2013-07-01

To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68 years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6 %) followed by HPV-31 (26.9 %), -6 (18.6 %), -58 (8.8 %), -18 (6.7 %), -66 (5.7 %), -52 and -53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7 %, 31.2 %, 44 % and 37.2 % of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.

The problem of false-positive human papillomavirus DNA tests in cervical screening

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Rebolj, Matejka; Pribac, Igor; Frederiksen, Maria Eiholm

2013-01-01

Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing...... will probably replace cytology in future primary cervical screening. However, HPV testing is associated with more frequent false-positive tests compared to cytology. False-positive tests are defined as positive screening tests which are not subsequently confirmed with high-grade CIN. Several authors have...

Assessment of high-risk human papillomavirus infections using clinician- and self-collected cervical sampling methods in rural women from far western Nepal.

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Derek C Johnson

Full Text Available Nepal has one of the highest cervical cancer rates in South Asia. Only a few studies in populations from urban areas have investigated type specific distribution of human papillomavirus (HPV in Nepali women. Data on high-risk HPV (HR-HPV types are not currently available for rural populations in Nepal. We aimed to assess the distribution of HR- HPV among rural Nepali women while assessing self-collected and clinician-collected cervico-vaginal specimens as sample collection methods for HPV screening.Study participants were recruited during a health camp conducted by Nepal Fertility Care Center in Achham District of rural far western Nepal. Women of reproductive age completed a socio-demographic and clinical questionnaire, and provided two specimens; one cervical-vaginal specimen using a self-collection method and another cervical specimen collected by health camp auxiliary nurse midwives during a pelvic examination. All samples were tested for 14 different HR-HPV mRNA and also specific for HPV16/18/45 mRNA.Of 261 women with both clinician- and self-collected cervical samples, 25 tested positive for HR-HPV, resulting in an overall HR-HPV prevalence of 9.6% (95% confidence Interval [CI]: 6.3-13.8. The overall Kappa value assessing agreement between clinician- and self-collected tests was 0.62 (95% CI: 0.43-0.81, indicating a "good" level of agreement. Abnormal cytology was reported for 8 women. One woman identified with squamous cell carcinoma (SCC, and 7 women with high grade squamous intraepithelial lesions (HSIL. Seven of the 8 women tested positive for HR-HPV (87.5% in clinician-collected samples and 6 in self-collected samples (75.0%.This is the first study to assess HR-HPV among rural Nepali women. Self-collected sampling methods should be the subject of additional research in Nepal for screening HR-HPV, associated with pre-cancer lesions and cancer, in women in rural areas with limited access to health services.

Human Papillomavirus and Vaccination in Cervical Cancer

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Kung-Liahng Wang

2007-12-01

Full Text Available Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN] evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3 and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA and bivalent Cervarix (GlaxoSmithKline, London, UK. This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.

High Smac/DIABLO expression is associated with early local recurrence of cervical cancer

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Arellano-Llamas, Abril; Garcia, Francisco J; Perez, Delia; Cantu, David; Espinosa, Magali; De la Garza, Jaime G; Maldonado, Vilma; Melendez-Zajgla, Jorge

2006-01-01

In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed de novo in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients. We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10–186). Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates. Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients

Parity as a cofactor for high-grade cervical disease among women with persistent human papillomavirus infection

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Jensen, K E; Schmiedel, S; Norrild, B

2013-01-01

BACKGROUND:Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent...... human papillomavirus (HPV) infection.METHODS:A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (~13 years) on cervical lesions was obtained from...