Positive hrHPV Test Research Articles

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing

Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Use of Virus Genotypes in Machine Learning Diagnostic Prediction Models for Cervical Cancer in Women With High-Risk Human Papillomavirus Infection

High-risk human papillomavirus (hrHPV) is recognized as an etiologic agent for cervical cancer, and hrHPV DNA testing is recommended as the preferred method of cervical cancer screening in recent World Health Organization guidelines. Cervical cancer prediction models may be useful for screening and monitoring, particularly in low-resource settings with unavailable cytological and colposcopic examination results, but previous studies did not include women infected with hrHPV. To develop and validate a cervical cancer prediction model that includes women positive for hrHPV infection and examine whether the inclusion of HPV genotypes improves the cervical cancer prediction ability. This diagnostic study included diagnostic data from 314 587 women collected from 136 primary care centers in China between January 15, 2017, and February 28, 2018. The data set was separated geographically into data from 100 primary care centers in 6 districts for model development (training data set) and 36 centers in 3 districts for model validation. A total of 24 391 women identified with positive hrHPV test results in the cervical cancer screening program were included in the study. Data were analyzed from January 1, 2022, to July 14, 2022. Cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was the primary outcome, and cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was the secondary outcome. The ability of the prediction models to discriminate CIN3+ and CIN2+ was evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. The calibration and clinical utility of the models were assessed using calibration plots and decision curves, respectively. After excluding women without screening outcomes, the study included 21 720 women (median [IQR] age, 50 [44-55] years). Of 14 553 women in the training data set, 349 (2.4%) received a diagnosis of CIN3+ and 673 (4.6%) of CIN2+. Of 7167 women in the validation set, 167 (2.3%) received a diagnosis of CIN3+ and 228 (3.2%) of CIN2+. Including HPV genotype in the model improved the AUROC by 35.9% for CIN3+ and 41.7% for CIN2+. With HPV genotype, epidemiological factors, and pelvic examination as predictors, the stacking model had an AUROC of 0.87 (95% CI, 0.84-0.90) for predicting CIN3+. The sensitivity was 80.1%, specificity was 83.4%, positive likelihood ratio was 4.83, and negative likelihood ratio was 0.24. The model for predicting CIN2+ had an AUROC of 0.85 (95% CI, 0.82-0.88), with a sensitivity of 80.4%, specificity of 81.0%, positive likelihood ratio of 4.23, and negative likelihood ratio of 0.24. The decision curve analysis indicated that the stacking model provided a superior standardized net benefit when the threshold probability for clinical decision was lower than 23% for CIN3+ and lower than 17% for CIN2+. This diagnostic study found that inclusion of HPV genotypes markedly improved the ability of a stacking model to predict cervical cancer among women who tested positive for hrHPV infection. This prediction model may be an important tool for screening and monitoring cervical cancer, particularly in low-resource settings.

Cytology and High-Risk Human Papillomavirus Test for Cervical Cancer Screening Assessment.

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly.

The role of high-risk HPV testing in cervical cancer surveillance

While high-risk HPV (hrHPV) testing is not formally recommended as a surveillance modality in patients with a history of cervical cancer, it is often performed in routine practice. It is unclear whether the presence of hrHPV infection after cervical cancer treatment is associated with recurrent disease. Patients with a cervical cancer diagnosis who were seen in a single institution between May 2012 and December 2019 were retrospectively identified. Squamous cell, adenocarcinoma, adenosquamous, and neuroendocrine histologies were included. Those with cancer progression within 3months of treatment or<1year of documented surveillance were excluded. Patients who had hrHPV testing performed were included in the primary outcome analysis. Of the 262 patients meeting inclusion criteria, 58 (22%) recurrences were diagnosed, and recurrence was most commonly detected by a surveillance imaging study (71%). Among the 169 patients that were tested for hrHPV during the surveillance period, 41 (24%) had at least one positive hrHPV test. Recurrent disease was diagnosed in 24 (14%). Of the 24 patients with recurrent disease, 5 (21%) had at least one positive hrHPV test during surveillance, versus 36 (24%) of 145 patients without recurrent disease (p=0.67). No recurrences were detected by hrHPV testing. Positive hrHPV testing in the surveillance setting was not associated with cervical cancer recurrence but did lead to additional studies and procedures. Our findings do not support the routine use of hrHPV testing for the evaluation of cervical cancer recurrence.

Diagnostic performance of immediate colposcopy among women with high-risk human papillomavirus (HPV) other than HPV 16/18 and normal cytology.

Persistent infection with 1 of 14 high-risk genotypes human papillomavirus (HPV) genotypes is the crucial for the development of high-grade cervical cancer precursors. The reassuring management of women with cytology negative, high-risk HPV (HrHPV) positive is important especially after the widespread use of HPV testing either as a cotest. The aim of our study was to compare the colposcopic biopsy results of women with HPV 16/18 with other Hr-HPV genotypes and determine positive predictive values (PPV) for CIN2+ of other HR HPV genotypes. We prospectively had included the women with negative cytology and positive Hr-HPV test other than HPV 16/18. Control group was composed of women with negative cytology positive test results for either HPV 16 or HPV 18. Women with HrHPV positive, cytology negative referred to immediate colposcopy. The prevalence of CIN1 and CIN2 is significantly higher in HPV 16/18 group than pooled other HrHPV group (34.1% vs 17.5%, P = 0.01 for CIN 1+; 14.8% vs 5.2%, P = 0.03 for CIN 2+). The prevalence of CIN3 was almost three fold in women with HPV 16/18 (9.1% vs 3.1%). PPV for CIN 2+ was 16.4 (9.1-27.3) for HPV 16, 11.7 (2-37.7) for HPV 18, 20 (3.5-55.7) for HPV 31, 11.1 (0.6-49.3) for HPV 51, 12.5 (0.6-53.3) for HPV 58 and 59. We showed the relative high PPV for CIN2+ in OHrHPV other than HPV 16/18 positive group among cytology negative population. HPV 33, 51, 58, 59 and 18 had similar PPV for CIN2+ in basal cytology negative population.

HPV co-testing as cervical screening test, Experience of Alweiya early detection cervical clinic: one-year Analysis

Objectives: The high-risk Human papilloma virus test with conventional cytology (HPVco-test) was firstly introduced in our institute at May 2019 so we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus test results in a screening woman and to assess the accuracy between cytology and Human papilloma virus testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program.&#x0D; Methods: A prospective study for women attending to early detection cervical clinic, during the period from May 2019 to May 2020. Patients who were sexually active were included in the study. Samples for conventional cytology and HPV by using real-time polymerase chain reaction technique for high risk types were taken concurrently. The prevalence of positive screening results and the difference in accuracy between two testing were estimated by McNemar’s χ2 test.&#x0D; Result: A total of 388 women were included in the study. The prevalence of positive test for hr-HPV was 2.1%(8) while the prevalence of abnormal cytology test was 19.1%(74), Concerning discordant pairs, 0.8%(3) of women had normal cytology with a positive hr-HPV test result and 17.8%(69) of women had abnormal cytology with a negative hr-HPV test result. A total of 311 (80.1%) women had normal cytology and negative hr-HPV test results. The proportion of women with abnormal cytology and positive hr-HPV test results was 1.3% (5 women). the difference in accuracy between the two results was statistically significant (&lt;0.0001). The prevalence of positive hr-HPV test decreased with increasing age, whereas the prevalence of abnormal cytology showed a bimodal age pattern.&#x0D; Conclusion: The prevalence of abnormal cytology was high to that of hr-HPV testing, which could not allow for the implementation of hr-HPV as a primary test in the national screening program in Iraq.

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland.

Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test. The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16months. hrHPV-negative women were scheduled for re-screening after 5years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55years old in 2012, and 40-60years old in 2017. In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P=.002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P=.220). In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.

Evaluation of the effectiveness of high-risk human papilloma self-sampling test for cervical cancer screening in Bolivia

BackgroundIn Bolivia the incidence and mortality rates of uterine cervix cancer are the highest in America. The main factor contributing to this situation is the difficulty of establishing and maintaining quality prevention programs based on cytology. We aimed to evaluate the effectiveness of HR-HPV testing on self-collected samples to detect cervical intra-epithelial neoplasia and identify the best combination of screening tests.MethodsA total of 469 women, divided in two groups, were included in this study. The first group included 362 women that underwent three consecutively primary screening tests: self-collected sampling for HR-HPV detection, conventional cervical cytology and visual inspection under acetic acid (VIA). The second group included 107 women referred with a positive HR-HPV test that underwent conventional cervical cytology and VIA. The presence of high grade intraepithelial lesion (CIN 2+) or invasive cancer was verified by colposcopy and biopsy.ResultIn the screening group the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer were 100, 76, 44% for the VIA, HR-HPV test and cytology, respectively. In the referred group, the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer by VIA and cytology were 100 and 81%, respectively.ConclusionsVIA and HR-HPV self-sampling were the best combination to detect CIN2+ lesions. Cytology analysis gave the poorest performance.

Prevalence of positive screening test results and agreement between cytology and human papillomavirus testing in primary cervical cancer screening in North-Western Romania.

Using data from a pilot study conducted in North-Western Romania, we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus (hr-HPV) test results in an ethnically diverse screening population and to assess the agreement between cytology and hr-HPV testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program. The cross-sectional pilot study included Roma women, other ethnic minorities, and women in rural remote areas. Samples were taken for liquid-based cytology and hr-HPV testing (Hybrid Capture 2 DNA test) by a mobile health unit. The prevalence of positive screening results and the agreement between cytology and hr-HPV testing were estimated by κ coefficient. A total of 1019 women were included in the study. The population prevalence of positive screening results was similar for both tests (12%). The prevalence of abnormal cytology increased with increasing age, whereas the prevalence of positive hr-HPV test showed a bimodal age pattern. Substantial differences in the prevalence of abnormal cytology were found by ethnicity, with highest prevalence in Romanian women (14%), followed by Roma women (6%) and women of other ethnicities (5%) (P = 0.002). Similar ethnic differences in the prevalence of positive hr-HPV test were not observed. The overall agreement of positive screening results between the two methods was fair (κ = 0.25; 95% confidence interval = 0.18-0.30, P < 0.001) and ranged from poor to substantial depending on the age group. The prevalence of abnormal cytology result was high and similar to the prevalence of positive hr-HPV test result, which could allow for the implementation of hr-HPV testing as a primary test in the cervical cancer screening program in Romania.

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark \u2013 the SHADE

BackgroundWomen living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark.MethodsFrom the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011–2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL.ResultsOf 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/μL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18–16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21–60.28)).ConclusionsThis prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/μL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.

HPV-based screening for cervical cancer among women 55-59 years of age

AimMany cervical cancers occurs among women over 65 and prevalence of HPV genotypes in this age cohort is sparingly studied. One aim of this study was to study the prevalence and distribution of HPV genotypes in women 55–59 years, with normal cytology when exiting the screening program. Secondly, HPV clearance as well as the value of HPV genotyping and/or liquid based cytology as triage tests for identifying histological dysplasia among women with persistent HPV was studied.MethodsWomen that exited the screening program with normal cytology, between the years 2012–2014, in Örebro County, Sweden, were invited to this study. A total of 2946 samples were analyzed with a broad-spectrum assay to detect both hrHPV and lrHPV in order to investigate the distribution of genotypes. In the consent group, women with a positive hrHPV test were offered a follow-up test and a cone biopsy for histological confirmation, and a follow up sample 6 months post cone.ResultsThe overall prevalence of hrHPV was 7.4% and 59% of them remained hrHPV positive in a follow-up test after 12 months. A total of 99 women had a cone biopsy done, where 19% showed histological dysplasia. HPV 53 was the most common genotype, and among women with histology confirmed LSIL or HSIL, HPV 31 was most common. A positive hrHPV result showed a PPV of 25% for LSIL+ and 12.5%for HSIL+. Using detection of HPV 16/18 genotypes as a triage test for hrHPV positive tests, indicated FNR for histological LSIL+ and HSIL+ of 94% and 87.5% respectively, whilst triage based on cervical cytology had a FNR of 69% for LSIL+ and 37.5% for HSIL+.ConclusionThe most common hrHPV genotypes among women 55–59 years of age were non HPV16/18 genotypes, and in this population, these genotypes represented most of the histological verified HSIL lesions. This result does not support the proposition of a HPV 16/18 triaging test after a positive hrHPV test as a marker of histological HSIL+ cervical lesions in women over 55 years of age. Similarly, cytological triage after a positive hrHPV showed no additional benefit in this population. Specific triaging tests should be validated to follow post-menopausal women with a positive hrHPV test.

CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions.

Background: Squamous intraepithelial lesions/cervical intraepithelial neoplasias (SIL/CIN) are high-risk human papilloma virus (hrHPV)-related lesions which are considered as high grade (HSIL/CIN2-3) or low grade (LSIL/CIN1) lesions according to their risk of progression to cervical cancer (CC). Most HSIL/CIN2-3 are considered as transforming hrHPV infections, so truly CC precursors, although some clear spontaneously. hrHPV testing has a high sensitivity for the detection of HSIL/CIN2-3 but a relatively low specificity for identifying transforming lesions. We aimed to determine whether the combination of CADM1, MAL and miR124 promoter methylation status assessed in histological samples can be used as a biomarker in the identification of transforming HSIL/CIN lesions. Design: 131 cervical biopsies, including 8 cases with no lesion and a negative hrHPV test result (control group), 19 low-grade (L)SIL/CIN1, 30 HSIL/CIN2, 60 HSIL/CIN3, and 14 CC were prospectively collected. hrHPV was detected and genotyped using the polymerase chain reaction (PCR)-based technique SPF10 HPV LIPA. A multiplex quantitative methylation-specific PCR (qMSP) was used to identify the methylation status of the CADM1, MAL, and miR124 promoter genes. Results: Significantly higher methylation levels of CADM1, MAL and miR-124 were found in HSIL/CIN2-3 and CC compared with normal and LSIL lesions. DNA methylation of at least one gene was detected in 12.5% (1/8) of normal samples, 31.5% (6/19) of LSIL/CIN1, 83.3% (25/30) of HSIL/CIN2, 81.6% (49/60) of HSIL/CIN3 and 100% (14/14) of CC (p < 0.001). The sensitivity and specificity for HSIL/CIN2-3 and CC of having at least one methylated gene were 84.6% and 74.0%, respectively. The sensitivity and specificity of the combination of at least one methylated gene and a positive hrHPV test were 80.7% and 85.1% for HSIL/CIN2-3 and CC, respectively. Conclusions: The methylation rate of CADM1, MAL and miR124 increases with the severity of the lesion. Further research is warranted to evaluate the usefulness of these biomarkers for the identification of transforming HSIL/CIN.

High-risk HPV detection and associated cervical lesions in a population of French menopausal women

BackgroundWith population ageing, post-menopausal women represent a new group to be considered in cervical cancer screening strategies, including the significance of High Risk (HR)-HPV detection. ObjectivesA retrospective analysis was conducted in a cohort of 406 menopausal women attending routine gynaecological consultation at the Hospital of Montpellier (France). Study designAll women benefited from a cervical smear and HR-HPV detection using Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV detection and risk factors associated with HR-HPV detection were analyzed. Evolution of both tests was evaluated in a sub-group of women with adequate follow-up. ResultsFive women (1.2%) had an abnormal cervical smear at baseline. HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology (9%). Risk factors associated with HR-HPV detection at enrolment were a previous history of Cervical Intraepithelial Neoplasia and a high socio-economic level, but not hormone replacement therapy. When cytology and HR-HPV detection were negative at enrolment, both remained negative for 95% (230/241) of women during follow-up (median duration of follow-up: 60 months). HR-HPV persistence was observed for 55% (18/33) of women with normal cytology and positive HR-HPV test. Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion (N = 7) had a positive HR-HPV test with or without abnormal cytology. ConclusionsHR-HPV was detected in 9.9% of menopausal women. HR-HPV detection was a better predictor of CIN2+ lesions than cytology in this population. Women with previous CIN history should benefit from HR-HPV testing and need long term follow-up.

Hybrid capture as a tool for cervical lesions screening in HIV-infected women: insights from a Brazilian cohort

IntroductionCervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. Methods723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. ResultsIncidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8–11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9–1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3–2.2) and 3.2-fold (95% CI 1.5–7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7–94.6] for 12 months and 80.9% [95% CI 77.2–84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9–100.0] for 12 months and 99.0 [95% CI 97.6–99.7] for 36 months). ConclusionsIncidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.

Use of immunohistochemical staining for p16 in gynecological cytology.

Use of immunohistochemical staining for p16 in gynecological cytology.

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

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

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

Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence.HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated. • To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field. We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed. The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN.We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN. We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

Primary HPV test screening in cervical cancer: a two-year experience of a single screening center in Latina (Italy).

The aim of this study was to evaluate the effect and performance of the new algorithm in cervical cancer screening program in two years' experience of Latina (Italy). MATERIALS AND MTHODS: The female population was divided into two groups, the first group was referred to PAP test and the second one to hr-HPV test according to national guidelines. In two years the participation mean rate increased among women aged 35-64 compared to women aged 25-34. The primary PAP test positive rate and hr-HPV test positive rate were 4.0% and 5.2%, respectively. The PAP test positive rate among hr-HPV+ women decreased from 2012 to 2013. Women with hr-HPV+/PAP+ were referred immediately to colposcopy and this rate was 1.2%. The predictive positive value for CIN2+ to colposcopy was 10.9% in 2012 and 9.1% in 2013, while the detection rate for CIN2+ was 1.6% in 2012 and 1.4% in 2013. The stratification of the female population leads to a decreased inappropriate therapeutic path while the combination of hr-HPV test with PAP test in woman aged 35-64 lets obtain high levels specificity and sensitivity results.