HPV Clearance Research Articles

A study of type-specific HPV natural history and implications for contemporary cervical cancer screening programs

BackgroundHPV testing is replacing cytology for cervical cancer screening because of greater sensitivity and superior reassurance following negative tests for the dozen HPV genotypes that cause cervical cancer. Management of women testing positive is unresolved. The need for identification of individual HPV genotypes for clinical use is debated. Also, it is unclear how long to observe persistent infections when precancer is not initially found. MethodsIn the longitudinal NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) Study, we observed the clinical outcomes (clearance, progression to CIN3+, or persistence without progression) of 11,573 HPV-positive women aged 30–65 yielding 14,158 type-specific infections. FindingsRisks of CIN3+ progression differed substantially by type, with HPV16 conveying uniquely elevated risk (26% of infections with seven-year CIN3+ risk of 22%). The other carcinogenic HPV types fell into 3 distinct seven-year CIN3+ risk groups: HPV18, 45 (13% of infections, risks >5%, with known elevated cancer risk); HPV31, 33, 35, 52, 58 (39%, risks >5%); and HPV39, 51, 56, 59, 68 (23%, risks <5%). In the absence of progression, HPV clearance rates were similar by type, with 80% of infections no longer detected within three years; persistence to seven years without progression was uncommon. The predictive value of abnormal cytology was most evident for prevalent CIN3+, but less evident in follow-up. A woman's age did not modify risk; rather it was the duration of persistence that was important. InterpretationHPV type and persistence are the major predictors of progression to CIN3+; at a minimum, distinguishing HPV16 is clinically important. Dividing the other HPV types into three risk-groups is worth considering.

Course of cervical intraepithelial neoplasia diagnosed during pregnancy.

Management of high-grade cervical intraepithelial neoplasia [CIN grade 2 or 3 (CIN2-3)] diagnosed during pregnancy is controversial. Monitoring with colposcopy and cytology every 8-12weeks is advised by the most current guidelines. This study analyzes the course of disease in pregnant women with abnormal cytologies or clinically suspicious cervixes. In total, 139 pregnant women, at a median age of 31years (range 19-49), treated at the Colposcopy Unit of the University Medical Center Hamburg-Eppendorf between 2011 and 2017 were identified. During pregnancy, at least one biopsy was performed on 70.5% of patients. In 84.7% of cases, CIN2-3 (CIN2 n = 14 (14.3%), CIN3 n = 69 (70.4%)) was detected, 7.1% (n = 7) of women were diagnosed with CIN1, while no dysplasia was found in 8.2% (n = 8) of cases. No interventions were necessary during pregnancy. Despite explicit invitation, only 72.3% of women with CIN2-3 attended postpartal consultations. While 61.7% showed persistent lesions, 5% were diagnosed with CIN1 and 33.3% with complete remission. During pregnancy, 68.7% of women with prepartal CIN2-3 were tested for HPV infection. Later, 49.1% were followed up postpartally by means of HPV testing and histology. HPV clearance was observed in 36.4% of women with complete histological remission. Postpartum conization was performed on 44.6% of patients with prepartal CIN2-3 diagnosis. CIN2-3 was histologically confirmed in 97.3% cases. Progression from persistent CIN3 to microinvasive carcinoma was observed in a single case. High-grade CIN lesions, diagnosed during pregnancy, show a high rate of regression postpartum; whereas, progression to carcinoma is rare. Close and continuous monitoring rarely has any therapeutic consequences. Compliance for postpartal follow-up needs to be improved.

DNA-HPV transition rate and related factors in HPV-infected women in Can Tho city, Vietnam.

To determine DNA-HPV transition rates and related factors in HPV-infected women 18-69years of age in Can Tho City from 2013 to 2018. Both a retrospective and a prospective cohort study were done. Interviews, gynaecological examinations and HPV testing by PCR (cervical fluid) were used to collect data. The results were recorded and compared with those of HPV in 2013 to assess the development of HPV over time. Transition was defined as conversion to HPV-positive state in 2018 from a negative state in 2013. No transition was defined as clearance of HPV when the positive 2013 result was negative in 2018 or when the result remained negative or positive in 2013 and 2018. Factors related to the change were analysed. Among a sample size of 204 cases, the average age of participants was 48.9±10.4years. Women >45 comprised 63.2% of participants; 82.8% lived with their husbands, 6.4% were divorced, and 2.9% lived apart from their husbands due to work. After 5years of observation, 16.2% of DNA-HPV cases had converted to HPV-positive state and 66.2% of DNA-HPV cases had cleared to HPV-negative state. Factors related to conversion to HPV-positive state were age≤45years (3.14 times higher risk of transition than in the >45 age group (95% CI: 1.12-8.8)); change of sexual partner (OR=3.75 (95% CI: 1.15-12.2)); change of sexual partner by husband (OR=3.69 (95% CI: 1.20-11.3); sexually transmitted diseases (OR=5.19 (95% CI: 1.09-24.8)); and a history of vacuum aspiration or dilation and evacuation abortion (OR=1.4 (95% CI: 0.29-6.4)). 16.2% of women with DNA-HPV transition converted to HPV-positive state. Changes in sexual habits increase the risk of developing HPV positivity.

Application of Oral Bacteriotherapy to Promote Anal HPV Clearance in HIV Positive Individuals

Application of Oral Bacteriotherapy to Promote Anal HPV Clearance in HIV Positive Individuals

Five-year risk of CIN3 after short-term HPV-DNA negativity in cytology-negative women: a population-based cohort study.

To assess the 5-year risk of high-grade lesions in women with a transient high-risk HPV infection. Population-based cohort study. HPV primary testing within population-based organised cervical cancer screening programmes. Italian women enrolled in seven pilot projects and attending the second round. On the basis of the cytology triage performed on HPV-positive women, immediate colposcopy or HPV repeat at 12months was recommended. Data were collected at the subsequent round 3-4years after HPV infection clearance. Rates of HPV infection, CIN2+ and CIN3+ detection at subsequent round after HPV clearance, and relative risks (RR) in comparison with HPV-negative women (with 95% confidence interval). Data on 1230 women (1027 aged 25-64years and 203 aged 35-64years) have been analysed. Overall compliance with repeat HPV testing was 84%. In comparison with HPV-negative women, those with a transient HPV infection had higher proportions of HPV positivity (15% versus 3.7%) and of CIN2+ lesions (0.87% versus 0.23%) in round two; most of these (7/10) were CIN2; no cancers were detected, and CIN3 occurred in 3/1230 (0.24%). HPV-based protocols for cervical cancer screening allow long intervals for HPV-negative women; it is important to monitor the clinical outcome in the women with transient high-risk HPV infection. CIN3 detection is similar to that observed in routine European cytology-based screening programmes (CIN3+: 2.7‰); 5-year intervals may provide reasonable protection but longer intervals are not recommended. A screening interval of 5years (but no longer) appears safe in women with transient HPV detection.

Association of age and viral factors with high-risk HPV persistence: A retrospective follow-up study

ObjectiveCervical HR-HPV persistence is the main risk factor for cervical cancer. We aimed to investigate the association of age and viral factors with HR-HPV persistence. MethodsFrom 2010 to 2017, 343,128 women underwent 390,411 tests performed by the Cervista HR-HPV assay (Data C3) and 157,123 women underwent 206,505 tests performed by the GenoArray HR-HPV assay (Data G14) in nine medical centers located in central and eastern China. We combined the test results and identified 9234 HPV-specific baseline-negative records for time-to-event analyses. The study endpoint event was defined as clearance of type/group-specific HPV. Therefore, hazard ratio (HR) < 1 indicated a higher risk of HPV persistence, which is contrary to the common meaning of HR. ResultsThe median persistence time was 375 and 541.5 days for Data C3 and Data G14, respectively. For every 5-year increase in age, a 15% (95% confidence interval [CI], 11%–19%) decrease in the clearance rate was observed only after 400 days of infection. For each additional co-infected HPV, the HR was 1.80 (95% CI, 1.63–1.97) on infection initiation but decreased by 22% (95% CI, 18%–26%) every 100 days. The HR of infection recurrence was 0.48 (95% CI, 0.32–0.72). The findings were consistent across different populations and test methods and were robust in sensitivity analysis. ConclusionsWe found a time-dependent association of age and viral factors with HPV clearance. Older age reduced HPV clearance only after 400 days of infection. Co-infection promoted HPV clearance in the beginning, but the effect attenuated and reversed as infection persisted. Recurrent same-type infection cleared slower than the previous one.

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.

Detoxification therapy of traditional Chinese medicine for genital tract high-risk human papillomavirus infection: A systematic review and meta-analysis.

BackgroundPersistence of high-risk human papillomavirus (hr-HPV) infections is the most critical risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). Treatment of persistent oncogenic HPV-positive women after 12–24 months follow-up is still controversy. Detoxification therapy of Chinese medicine (DTCM) has been conducted recently. However, the conclusions are still unclear. We planned to conduct a systematic review and meta-analysis to explore DTCM in the treatment of persistent hr-HPV infections.MethodsNine electronic databases were systematically searched from their inception to 30 September 2018. Randomized controlled trials comparing DTCM with follow-up or placebo were included. Risk of bias was assessed by the Cochrane ‘Risk of Bias’ tool. Review Manager 5.3 was used for statistical analyses. Relative ratios (RR) and 95% confidence intervals were used for dichotomous data, and the mean difference (MD) was used for continuous data. We assessed the quality of trials by the GRADE.ResultsSeventeen RCTs from 2011 to 2018 with 1906 participants were included. The evidence showed that DTCM had a pooled efficacy difference in favor of increasing the HPV clearance rate compared to placebo groups (RR = 2.62, 95% CI 1.28 to 5.33, very low quality) and follow-up groups (RR = 1.88, 95% CI 1.60 to 2.22, low quality). The median HPV persistence tended to decline from 50% within six months to 41.5% at 12 months, and 31.5% at 24 months. A significantly increased regression rate of CIN was found in the DTCM compared with placebo groups (RR = 3.61, 95% CI 1.21 to 10.83, very low quality) and follow-up groups (RR = 1.79, 95% CI 1.31 to 2.45, very low quality). Additionally, we found DTCM have an impact on TNF-α (MD = 2.99, 95% CI 1.90 to 4.07; very low quality), IFN-α (MD = 3.47, 95% CI 2.42 to 4.52; very low quality), CD4+/CD8+ cells (MD = 0.21, 95% CI 0.05 to 0.37; very low quality) compared with follow up groups in some trials with small sample sizes. The major adverse events were genital mucosal irritation symptoms (10%, 5/50).ConclusionsDTCM have favorable outcomes on improving the HPV clearance rate, increasing the regression rate of CIN, and impacting the proportion of some immune cells and cytokine levels. However, most of the evidence was of low quality. Any future high-quality trials and a more extended follow-up period of 24 months or more should be performed.

HPV vaccine in the treatment of usual type vulval and vaginal intraepithelial neoplasia: a systematic review

BackgroundHPV DNA is found in almost 80% of VIN/VaIN. Current management is inadequate, with high recurrence rates. Our objective was to review the literature regarding the role of HPV vaccine in secondary prevention and treatment of VIN/VaIN.MethodsDatabase searches included Ovid Medline, Embase, Web of Science, The Cochrane Library and Clinicaltrials.gov. Search terms included HPV vaccine AND therapeutic vaccine* AND VIN OR VAIN, published in English with no defined date limit. Searches were carried out with a UCL librarian in March 2018. We included any type of study design using any form of HPV vaccine in the treatment of women with a histologically confirmed diagnosis of VIN/VaIN. We excluded studies of other lower genital tract disease, vulval/vaginal carcinoma and prophylactic use of vaccines. The outcome measures were lesion response to vaccination, symptom improvement, immune response and HPV clearance.ResultsWe identified 93 articles, 7 studies met our inclusion criteria; these were uncontrolled case series. There were no RCTs or systematic reviews identified. Reduction in lesion size was reported by all 7 studies, symptom relief by 5, HPV clearance by 6, histological regression by 5, and immune response by 6.ConclusionsThis review finds the evidence relating to the use of HPV vaccine in the treatment of women with VIN/VaIN is of very low quality and insufficient to guide practice. Further longitudinal studies are needed to assess its use in prevention of progression to cancer.

Cervical human papillomavirus among 19 753 women attending gynecological department of a major comprehensive hospital in north Anhui China 2013-2016: Implication for cervical cancer screening and prevention.

Our study aimed to assess the prevalent, incident, and persistent infection, and clearance of HPV among 19 753 individual women attending the gynecological department at a major comprehensive hospital. HPV 16, 52, and 58 ranked top three types with the highest prevalence and incidence. The prevalence of high-risk (HR) HPV peaked among women aged 15 to 19 years, then sharply decreased with age, stabilized among women aged 25 to 44 years, and then surged again among women aged 45 years and older. HR HPV infection were more likely to be prevalent (15.9% vs 1.3%, P < 0.001), incident (17.3 vs 2.0 per 1000 person-months, P < 0.001), and persistent (33.0% vs 24.2%, P = 0.033), and less likely to clear (88 vs 115 per 1000 person-months, P = 0.040) compared to low-risk HPV types. The majority of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education and counseling about HPV infection and its implications for women detected with HPV at clinical settings are warranted.

A prospective cohort study to evaluate immunosuppressive cytokines as predictors of viral persistence and progression to pre-malignant lesion in the cervix in women infected with HR-HPV: study protocol

BackgroundCervical cancer (CC) is caused by a persistent infection of high-risk human papillomavirus (HR-HPV). While most HPV infections are transient, persistent HPV infections are a significant health problem in Mexico. With an estimated HPV prevalence of 10% among women in reproductive age, approximately 25% of these women present at least a positive result in triage test, which according to previous studies is expected to be confirmed as positive CIN-2/3. The immune system has a key role in the natural history of HPV infection; alterations in the cellular immune response are responsible for the failure to eliminate HPV. The objective of this project is to assess the prognostic value of detecting immune markers (IL-10, IL-4, TGFβ1, IFNγ, IL-6, and TNFα), the expression of HPV-HR E6/E7 proteins, and the viral load at the cervical level with respect to the persistence or clearance of HR-HPV infection, and the regression or progression of a cervical premalignant lesion.MethodsA dynamic cohort study is being conducted in women with colposcopic, cytological, and histopathological results negative for squamous intraepithelial lesion (SIL) in the cervix and a positive HPV test; the subjects will be followed-up for 5 years, period from which 3 years have already elapsed, with yearly studies (colposcopy, cytology, and histopathology diagnosis, along with molecular HPV test, quantification of viral load and of IL-10, IL-4, TGFβ1, INFγ, IL-6, and TNFα levels, along with the expression of the HR-HPV E6/E7 proteins in the cervix as a viral marker. The outcome will be categorized as viral persistence or clearance; and as SIL persistence, progression, or regression. Binomial and/or multinomial regression models adjusted for potential confounders will be used, associating the relative risk of the outcome with the immune and viral markers evaluated.DiscussionThis research will generate knowledge about immune markers with predictive value for the persistence and clearance of HPV, which will improve the triage of positive HPV women and thus reduce the economic burden for the Mexican health system imposed by the management of high-grade SIL and CC cases, which are still detected in late stages.

Influence of intrauterine dispositive in human papillomavirus clearance

Introduction: An important inverse relation between IUD use and risk of cervical cancer has been proved. Women who used IUD had half the risk of developing cervical cancer. The mechanism how IUD is a protector factor is still unknown. Could be improving the clearance of HPV infection or stopping progression to cancer from preneoplasic lesion.The aim of the study is to check if IUD increases HPV clearance, that is, checking if after 1 year HPV infection disappears in more patients using IUD than those not using it.Study design: This is a cohort case-control prospective study, carried out in Universitary Hospital La Zarzuela in Madrid, Spain, performed between October 2015 and April 2018.No pregnant women between 25–50 years old, with HPV cervical infection were enrolled. We separated the participants into two groups: an IUD group, with women starting using IUD and non IUD group, with women using any other contraceptive method or none. HPV genotyping of cervical cytology samples were performed initially on enrolment day and one year after.Results: 254 participants were enrolled at the beginning of the study, 85 in the IUD group and 169 in the control group (non IUD). 179 participants completed the study, 54 (31%) in IUD group and 120 participants in non IUD group (69%).38 women from IUD group cleared HPV infection (69.5%) and 65 women from control group cleared it (54.2%) (p = 0.044).An association in logistic regression was observed in HPV clearance with different factors. Firstly, higher percentage of patients with IUD clear the HPV infection than those in control group significantly associated (OR = 0.698, CI 95%; 0.251–0.998, p = 0.046). Clearance was higher in patients with low-risk HPV infection comparing with high risk HPV (OR = 1.078, CI 95%; 1.126–4.6.281, p = 0.026) and in patients with only one HPV type than those with more than one (OR = 0.194, CI 95%; 0.084–0.403, p < 0.001).Conclusions: In Spanish women with HPV infection, the HPV clearance between IUD and non IUD groups show results with statistical significance, patients with IUD have higher clearance rates. There were differences also between suffering one HPV type or more than one, and having low-risk HPV or high-risk HPV infection.

Association of cervical microbial community with persistence, clearance and negativity of Human Papillomavirus in Korean women: a longitudinal study

The present study aimed to identify the cervical microbes that are associated with HPV negativity, HPV clearance and HPV persistence and to assess the microbes’ longitudinal associations as related to HPV infection dynamics among Korean women. We enrolled 41 women with 107 samples, and classified them according to the HPV infection dynamics: HPV negativity (21 samples, 10 subjects), HPV clearance (42 samples, 15 subjects), and HPV persistence (44 samples, 16 subjects). Cervical swabs were collected at the baseline and six-month-interval follow-up visits. HPV positivity was determined by HPV DNA HC2 assay, and the microbiome was analyzed using 16SrRNA pyrosequencing, linear discriminant analysis effect size and multivariate logistic analysis. In the multivariate logistic analysis results, Lactobacillus crispatus (multivariate OR (mOR) = 8.25, 95% CI 2.13~32.0) was predominant in the HPV-negative group. We observed that Eubacterium eligens (mOR = 11.5, 95% CI 1.31~101.4), Gardnerella vaginalis (mOR = 17.0, 95% CI 2.18–131.8), and Ureaplasma urealyticum (mOR = 7.42, 95% CI 1.3–42.46) had the strongest associations with HPV clearance, and Lactobacillus johnsonii (mOR = 16.4, 95% CI 1.77–152.2) with HPV persistence. Overall, greater diversity was observed in HPV-persistence than in HPV-negative women. Our findings suggest that the presence and prevalence of a specific cervical microbiome are factors involved in HPV dynamics.

Dynamics and Determinants of HPV Infection: The Michigan HPV and Oropharyngeal Cancer (M-HOC) Study

IntroductionHuman papillomavirus (HPV) is the primary cause of cervical and other anogenital cancers and is also associated with head and neck cancers. Incidence of HPV-related oropharyngeal squamous cell cancers (OPSCCs)...

Abstract CT080: Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression

Abstract Introduction : The poly-gamma-glutamic acid (γ-PGA) is a safe and edible polypeptide that is naturally synthesized by Bacillus subtilis 1 and has long been taken up as an ingredient of fermented soybean foods. The γ-PGA as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to enhance natural killer (NK) cell activity and inhibit tumors. Although CIN-1 typically represents transient infection, about 10% of CIN-1 is found to progress to CIN-3, and HPV infection persists and leads to high grade cervical dysplasia in some women with CIN-1. The aim of this study was to investigate the efficacy and safety of γ-PGA and impact γ-PGA on the immune system including PD-1 / PD-L1 in patients with CIN 1. Material &amp; Methods : We conducted a multi-center, randomized, double blind, placebo control, parallel designed, phase 2b study. Participants were randomly assigned to one of two groups: half received oral solution containing 1500 mg of γ-PGA; half received a placebo. Each participants took one dose every 24 hours for 4 weeks. Colposcopy with biopsy was assessed at the time of screening and 12 weeks. Blood samples were drawn at the initial treatment and at the 4th, 8th, 12th weeks after treatment. The primary endpoint of the study was histologic regression rate between screening and 12th weeks. The secondary endpoint were cytologic response rate, HPV clearance, change of immune responses and PD-1/PD-L1 expression. Result From April 2013 to December 2015, 254 patients were screened and a total of 200 patients participated in the study. Of these, Of 101 women in γ-PGA group, 42 (42.4%) women experienced histologic regression, whereas 26 (27.1%) in the control group experienced histologic regression, showing statistically significant differences (p=0.018). In the γ- PGA group, HPV clearance was found in 37 (43.5%) of the 85 high-risk HPV infected patients, showing a meaningful difference compared to the control group showing HPV clearance of 20 (26.7%) out of 75 (p=0.026). However, there was no significant difference between the two groups in terms of cytologic regression rate and type specific clearance of HPV. The immunologic factors including NK cell activity, CD8 cell count and PD-1/PD-L1 expression, which are thought to be related to the therapeutic mechanism of γ- PGA, showed no significant difference between the two groups. Conclusion : The γ-PGA enhance histologic regression in CIN-1 patients and showed the possibility of non-invasive medical treatment. In addition, γ-PGA has shown its potential as a treatment for high-grade CIN or cancer in the future as it has been shown to be effective against high-risk HPV infection. Citation Format: Hyun-Woong Cho, Yung-Taek Ouh, Jin Hwa Hong, Jae Kwan Lee, Jae-Won Jeon, Moon-Hee Sung. Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT080.

19 - Electrocautery ablation of anal HSIL: correlation of treatment outcomes with histological features and HPV genotypes

Background Electrocautery ablation (EA) is a widely used treatment modality for HPV-induced anal high-grade squamous intraepithelial lesions (HSIL). Roughly half of the targeted HSILs persist or recur following ablation. Several clinical characteristics have been linked to EA resistance; however, there is little data on whether and how ablation outcomes are affected by lesional histology and HPV genotypes. Methods Among lesions that responded to EA and those that recurred, we compared mitotic activity, type of dysplasia (classic vs. keratinized) and degree of dysplasia (AIN2 vs. AIN3). HPV genotypes were tested using cytology samples. Results 97 HIV-infected patients with HSIL underwent EA and surveillance. Upon follow-up (median 10 months, range 5–37), 44 (45%) patients revealed benign or LSIL at the prior ablation site (EA-sensitive group), whereas 53 (55%) revealed HSIL (EA-resistant group). Age, gender, and race distribution were similar regardless of ablation outcomes. The EA-sensitive group tended to have solitary lesions (60%), non-16/18 h-HPV infection (68%), and HPV clearance (18%), whereas the EA-resistant group had multiple synchronous lesions (81%) and HPV16/18 infection (57%). Compared to EA-sensitive lesions, resistant ones were characterized by higher mitotic activity (mean 7 vs. 3/HPF), a higher percentage of AIN3 (70% vs. 36%), as well as the keratinized dysplasia (74% vs. 48%). Conclusions Anal HSIL ablation resistance is associated with multiple synchronous lesions, HPV16/18 infection, high mitotic activity, AIN3, and keratinized dysplasia. Patients with these types of lesions are at high risk of recurrence and warrant careful surveillance.

The impact of male circumcision on the natural history of genital HPV infection: a prospective cohort study

Objective: To analyze the correlation between circumcision and incidence and clearance of male genital HPV infection. Methods: From May to July 2014, 18-55 year old men who had sexual behavior history were recruited from the general population in Liuzhou, Guangxi to set up a cohort. Totally, 113 circumcised and 560 uncircumcised men were enrolled and interviewed using a questionnaire (including information on demographic characteristics and sexual behaviors), then they were followed-up with 6-month interval for 2 times. On each visit, specimens of male external genitalia were collected and genotyped for HPV DNA. The differences of incidence and clearance of genital HPV infections between circumcised and uncircumcised men were analyzed by Log-rank test. Cox regression was used to analyze the relationship between circumcision and incidence and clearance of HPV infection. Results: The median age (P(25), P(75)) of circumcised and uncircumcised men were 28 (24, 35) and 32 (24, 31), respectively. The incidences of any HPV infections were 9.1 (95%CI: 2.4-15.7) and 8.4 (95% CI: 5.6-11.2) per 1 000 person-months (χ(2)=0.10, P=0.758), respectively. The clearance of circumcised men [136.3 (95%CI: 70.0-202.7) per 1 000 person-months] was higher than that in uncircumcised men [89.6 (95%CI: 65.9-113.3) per 1 000 person-months] (χ(2)=8.19, P=0.004). In multivariate COX regression analysis, compared with uncircumcised men, circumcised men had higher possibility to clear any HPV infections (HR: 2.41, 95%CI: 1.30-4.46). Compared with men having one sexual partner, people having more than 4 sexual partners had lower possibility to clear any HPV infections (HR: 0.49, 95%CI: 0.25-0.96). Compared with 18-25 years old men, men aged 26-35 years old had higher possibility to clear high-risk HPV infections (HR: 2.14, 95%CI: 1.08-4.23). Conclusion: Circumcised and uncircumcised men had similar incidence of genital HPV infection, whereas, men conducted circumcision and having fewer sexual partners could increase the clearance of genital HPV infections.

Clearance and persistence of the human papillomavirus infection among Cameroonian women.

Objective:Persistent infection with human papillomavirus is the prerequisite for the development of cervical precancerous and cancerous lesions. The aim of this study was to determine the time-to-viral clearance in a population of human papillomavirus–infected Cameroonian women and to examine the possible predictors of viral persistence.Methods:We conducted a prospective cohort study based on a population of human papillomavirus–positive women having previously been recruited in a self-human papillomavirus-based cervical cancer screening campaign, who were invited for a control visit at 6 and 12 months. We determined human papillomavirus clearance using self-sampling (Self-HPV) and physician-sampling (Dr-HPV), which were analyzed with a point-of-care assay (GeneXpert® IV; Cepheid, Sunnyvale, CA, USA). Logistic regression was performed to assess the relationship between sociodemographic and clinical characteristics with HPV clearance according to the two sampling techniques.Results:A total of 187 participants were included in the study. At the 12 months follow-up, 79.5% (n = 104) and 65.3% (n = 86) had cleared their human papillomavirus infection according to Dr-HPV and self-HPV, respectively (p = 0.001). Only parity (>5 children) was statistically associated with viral persistence (p = 0.033). According to Dr-HPV, clearance of women treated with thermoablation at 12 months was of 84.1% versus 70.2% for non-treated women (p = 0.075).Conclusion:The human papillomavirus clearing rates found in our study are close to those found in other studies worldwide. Parity was significantly associated with human papillomavirus persistence. Larger, prospective studies are needed to confirm our results.

Predictors of HPV incidence and clearance in a cohort of Brazilian HIV-infected women.

Persistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents a higher rate of persistent infections and an earlier progression to cancer. We aimed to evaluate HR-HPV prevalence, incidence and clearance, and its association with HIV viral suppression, immunological response and other risk factors among WLHA followed at an STD/HIV reference center. This was a cohort study conducted at a reference center for STD/AIDS in Northeastern Brazil from September 2013 to September 2015. Follow-up visits were conducted at 6 and 12 months after enrolment, where socio-epidemiological data were obtained. Cervical samples were collected for conventional cytology and HPV DNA research (PCR COBAS® Roche) in addition to blood samples for CD4+ T lymphocyte count and HIV viral load. We prospectively evaluated 333 women. HR-HPV DNA prevalence was 33.3% at baseline. HPV-16 was present in 5.1%, HPV-18 in 3.9% and 29.4% WLHA had other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The HR-HPV incidence during the follow-up was 10.8%, at the 6-month visit was 7.7% and at the 12-month visit was 3.7%. Variables associated with HR-HPV incidence were: nulliparity, combined oral contraceptive use and detectable HIV viral load. The HR-HPV clearance rate was 41.7% and was associated with age >30 years and lymphocyte T CD4 count >500 cells/mm3 at enrolment. These findings contribute to the knowledge about a group of women that need more careful HPV screening and describe the association between an efficient immunological response and HIV viral suppression with lower incidence and increased clearance of HR-HPV.

HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis

Although most cervical human papillomavirus type16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infectedcase-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.