Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.

Human Papillomavirus Antibody Levels Following Vaccination or Natural Infection Among Young Men Who Have Sex With Men.

BACKGROUND: Australia introduced a school-based gender-neutral human papillomavirus (HPV) vaccination program for girls and boys aged 12-13 years in 2013. We examined HPV type-specific antibody levels in unvaccinated young men who have sex with men (MSM) with natural infection and compared these with levels in those vaccinated against HPV. METHODS: Serum specimens at baseline were collected from MSM aged 16-20 years in the HYPER1 (Human Papillomavirus in Young People Epidemiological Research) and HYPER2 studies, conducted in 2010-2013 and 2017-2019, respectively. Merck's 4-plex HPV competitive Luminex Immunoassay was used to quantify HPV6-, HPV11-, HPV16-, and HPV18-specific antibodies. We compared antibody levels for each HPV genotype between unvaccinated men (HYPER1) and vaccinated men (HYPER2) using the Mann-Whitney U test. RESULTS: There were 200 unvaccinated men and 127 vaccinated men included in the analysis. Median antibody levels among vaccinated men were significantly higher than levels among unvaccinated men for HPV6 (223 milli-Merck units per milliliter [mMU/mL] vs 48 mMU/mL, P < .0001), HPV11 (163 mMU/mL vs 21 mMU/mL, P < .0001), HPV16 (888 mMU/mL vs 72 mMU/mL, P < .0001), and HPV18 (161 mMU/mL vs 20 mMU/mL, P < .0001). Antibody levels did not change over time for up to 66 months for all 4 genotypes among vaccinated men. CONCLUSIONS: Among young MSM vaccinated with the quadrivalent HPV vaccine, antibody levels for HPV6, HPV11, HPV16, and HPV18 were significantly higher than those in unvaccinated MSM following natural infection. Antibody levels following vaccination appeared to remain stable over time. CLINICAL TRIALS REGISTRATION: NCT01422356 for HYPER1 and NCT03000933 for HYPER2.

Sexual behaviours associated with incident high-risk anal human papillomavirus among gay and bisexual men.

OBJECTIVE: High-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia. METHODS: GBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method. RESULTS: Between 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43-56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (p<0.001), having a higher number of recent RAI partners regardless of condom use (p<0.001 for both), preference for the receptive position during anal intercourse (p=0.014) and other non-intercourse receptive anal sexual practices, including rimming, fingering and receptive use of sex toys (p<0.05 for all). In multivariable analyses, being HIV-positive (HR 1.46, 95% CI 1.09 to 1.85, p=0.009) and reporting condom-protected RAI with a higher number of sexual partners (p<0.001) remained significantly associated with incident HRHPV. When stratified by recent RAI, non-intercourse receptive anal practices were not associated with incident HRHPV in men who reported no recent RAI. CONCLUSION: GBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually active older GBM. TRIAL REGISTRATION NUMBER: ANZCTR365383.

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men.

BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR365383).

Prevalence of anal cytological abnormalities and high-risk human papillomavirus prevalence in kidney transplant recipients: A cross-sectional study.

BACKGROUND: Transplant recipients are at high-risk of anal squamous cell cancer. We aimed to estimate the prevalence of high-risk human papillomavirus (HPV) and high-grade squamous intraepithelial lesion (HSIL) and assess characteristics associated with results METHODS: We recruited kidney transplant recipients in a single-center, 2015-2018. Participants completed a clinical questionnaire and received an anal-swab sent for HPV-DNA and cytological testing RESULTS: A total of 97 (74%) of 125 recipients approached consented to participate. Participants were median 47 (IQR 40-55) years, 60% male and median 4.5 (IQR .9-13) months-since-transplant. Of 86 assessable samples, at least one HPV genotype was detected in 15 (17%) participants; 1 (1%) HPV16, 8 (9%) other high-risk HPV. Of 76 assessable cytology samples, 9 (12%) showed evidence of abnormality; 1 (1%) HSIL, 1 (1%) atypical-squamous-cells, cannot exclude HSIL. Both HSIL recipients had high-risk HPV and biopsy confirmed HSIL. High-risk HPV was detected in six (9%) recipients with normal cytology. History of sexually transmitted infection, and abnormal cervical pap smear in women, was associated with high-risk HPV and HSIL CONCLUSIONS: High-risk HPV and HSIL testing may identify kidney transplant recipients at higher risk of anal cancer. Longitudinal studies are needed to describe the natural history of anal cancer in transplant recipients.

Quadrivalent human papillomavirus vaccination successfully reduces the prevalence of vaccine-targeted genotypes in a young, vaccine-eligible-age sample of Australian females.

Background The prevalence of genital tract vaccine-type human papillomavirus (HPV) is on the decline due to high vaccine uptake through the national HPV immunisation program in Australia. The aim of this study was to investigate HPV vaccine coverage and factors associated with HPV in a vaccine-eligible sample of young Australian females. METHODS: Females aged 16-25 years were recruited into the Young Female Health Initiative study, a young women's health study, via Facebook advertising from 2012 to 2017. Sexually active participants were asked to provide a self-collected vaginal swab for the detection of HPV DNA; positive samples were genotyped. Self-reported HPV vaccination status was confirmed by the National HPV Vaccination Program Register. Outcomes of the study were HPV acquisition and genotype, HPV vaccination status and factors associated with HPV. RESULTS: Overall, 22.8% of samples (95% confidence interval (CI) 17.8-27.8%; n = 62/272) were positive for any HPV DNA, of which 19.1% (95% CI 14.4-23.8%; n = 52/272) were oncogenic types. HPV 16 was detected in three samples (1.1%; 95% CI -0.1%, 2.3%; two not HPV vaccinated and one vaccinated after sexual debut). Early sexual debut (<16 years) and multiple sexual partners were independently associated with an increased risk of any HPV. CONCLUSIONS: In a community sample of vaccine-eligible-age females with a high vaccine uptake, the prevalence of vaccine-related HPV genotypes is extremely low. Early sexual debut and multiple sexual partners are positively associated with HPV, underscoring the importance of vaccination at the routinely recommended age of 12-13 years for best vaccine impact.

Incidence, Clearance, and Persistence of Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Implications for Human Papillomavirus Vaccination.

BACKGROUND: Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. METHODS: Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. RESULTS: Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. CONCLUSION: Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.

Very Low Prevalence of Vaccine Human Papillomavirus Types Among 18- to 35-Year Old Australian Women 9 Years Following Implementation of Vaccination.

Introduction: A quadrivalent human papillomavirus vaccination program targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of 14-26 year olds through 2009. We evaluated the program's impact on HPV prevalence among women aged 18-35 in 2015. Methods: HPV prevalence among women aged 18-24 and 25-35 was compared with prevalence in these age groups in 2005-2007. For women aged 18-24, we also compared prevalence with that in a postvaccine study conducted in 2010-2012. Results: For the 2015 sample, Vaccination Register-confirmed 3-dose coverage was 53.3% (65.0% and 40.3% aged 18-24 and 25-35, respectively). Prevalence of vaccine HPV types decreased from 22.7% (2005-2007) and 7.3% (2010-2012), to 1.5% (2015) (P trend < .001) among women aged 18-24, and from 11.8% (2005-2007) to 1.1% (2015) (P = .001) among those aged 25-35. Conclusions: This study, reporting the longest surveillance follow-up to date, shows prevalence of vaccine-targeted HPV types has continued to decline among young women. A substantial fall also occurred in women aged 25-35, despite lower coverage. Strong herd protection and effectiveness of less than 3 vaccine doses likely contributed to these reductions.

The role of human papillomavirus in p16-positive oral cancers.

BACKGROUND: The aim of this study was to identify the presence and frequency of human papillomavirus (HPV) nucleic acid in p16-positive oral squamous cell carcinomas (OSCCs), to assess whether the virus was transcriptionally active and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC. METHODS: Forty-six OSCC patients treated between 2007 and 2011 with available formalin-fixed paraffin-embedded (FFPE) specimens were included. Twenty-three patients were positive for p16 by immunohistochemistry (IHC) and these were matched with 23 patients with p16-negative tumours. Laser capture microdissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high-risk HPV types using a PCR-ELISA method based on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16 and HPV-18 E6 region. Genotyping of HPV-positive cases was performed using a reverse line blot hybridization assay (Inno-LiPA). RNAScope® (a chromogenic RNA in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high-risk HPV types for detection of transcriptionally active virus. RESULTS: HPV DNA was found in 3 OSCC cases, all of which were p16 IHC-positive. Two cases were genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH. CONCLUSION: We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non-viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC.

Human Papillomavirus Prevalence in Unvaccinated Heterosexual Men After a National Female Vaccination Program.

Background: In Australia, high uptake of the quadrivalent human papillomavirus (4vHPV) vaccine has led to reductions in the prevalence of human papillomavirus (HPV) genotypes 6, 11, 16, and 18 in women and girls aged ≤25 years. We evaluated the impact of the program impact on HPV prevalence in unvaccinated male subjects. Methods: Sexually active heterosexual male subjects aged 16-35 years were recruited in 2014-2016. Participants provided a self-collected penile swab sample for HPV genotyping (Roche Linear Array) and completed a demographic and risk factor questionnaire. Results: The prevalence of 4vHPV genotypes among 511 unvaccinated male subjects was significantly lower in those aged ≤25 than in those aged >25 years: 3.1% (95% confidence interval, 1.5%-5.7%) versus 13.7% (8.9%-20.1%), respectively (P < .001); adjusted prevalence ratio, 0.22 (.09-.51; P < .001). By contrast, the prevalence of high-risk HPV genotypes other than 16 and 18 remained the same across age groups: 16.8% (95% confidence interval, 12.6%-21.9%) in men aged ≤25 years and 17.9% (12.4%-25.0%) in those aged >25 years (P = .76); adjusted prevalence ratio, 0.98, (.57-1.37; P = .58). Conclusions: A 78% lower prevalence of 4vHPV genotypes was observed among younger male subjects. These data suggest that unvaccinated men may have benefited from herd protection as much as women from a female-only HPV vaccination program with high coverage.

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. METHODS/DESIGN: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. DISCUSSION: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.

Antibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men.

Men who have sex with men (MSM) are at risk for human papillomavirus (HPV)-related anal cancer. Few data exist on antibody responses following incident anogenital infection with HPV in teenage MSM. A cohort of 200 MSM aged 16-20 years from Melbourne, Australia were assessed at baseline, 3, 6 and 12 months. At each visit anal and penile swabs were collected for HPV DNA and serum for HPV antibodies for genotypes 6, 11, 16 and 18 (Merck's Multiplex Assays using Luminex). The main outcome, seroconversion, was defined as the detection of HPV antibodies following a negative antibody result for the same HPV type at baseline. The seroincidence rates for HPV types 6, 11, 16 and 18 were: 19 (95% CI 12-26), 7 (3-12), 4 (1-8) and 6 (3-11) per 100 person-years, respectively. Men who experienced incident anal HPV infections from types 6/11 were significantly more likely to develop serum antibodies to the same HPV type(s) than those who experienced incident anal infections from types 16/18 [73 vs. 18%, odds ratio (OR) = 15, 95% CI: 2-118]. The median time between incident anal HPV infection and seroconversion for HPV 6, 11, 16 and 18 was: 91, 38, 161 and 182 days, respectively. Antibody responses against HPV types 6/11 were significantly more likely to occur following incident anal compared with incident penile infection with HPV types 6/11 (OR = 6, 95% CI: 2-21). The likelihood of antibody responses following anogenital HPV infections depends on the HPV type and site of infection.

Anal HPV detection in men who have sex with men living with HIV who report no recent anal sexual behaviours: baseline analysis of the Anal Cancer Examination (ACE) study.

OBJECTIVES: Men who have sex with men (MSM) living with HIV are at high risk of infection with high-risk human papillomavirus (HPV), the cause of anal cancer. We assess whether anal HPV DNA detection is related to recent anal sexual activity, what types of anal sexual activity or the persistence of HPV genotypes. METHODS: We analysed anal swabs taken at the baseline of a 2-year prospective anal cancer screening study of MSM living with HIV from four HIV clinics in Melbourne, Australia. Anal HPV detection was stratified by age and anal sexual behaviours. RESULTS: 281 anal swabs were included in the analysis. The majority (80%, 95% CI 75 to 84) of men were positive for any HPV; 59% (95% CI 53 to 65) were positive for high-risk HPV (hr-HPV) genotypes; and 31% (95% CI 26 to 36) men were positive for HPV 16 and/or 18 with no significant differences according to age groups (p>0.261). In men who reported no receptive anal sexual activity in the last six months (22%), hr-HPV was found in 53% (95% CI 41 to 65) for no anal sexual activity versus. 60% (95% CI 54 to 67) for anal sexual activity (p=0.320). HPV 16 and/or 18 was found in 26% (95% CI 16 to 38) for no anal sexual activity versus. 32% (95% CI 27 to 39) for anal sexual activity (p=0.320). CONCLUSIONS: Anal HPV in MSM living with HIV is detected in the majority of men throughout all age groups. Anal HPV detection remains high even in men reporting no anal sexual activity in the preceding six months.

Endocervical adenocarcinoma in situ presenting in fundal endometrial polyp: the mother of all skip lesions.

A 38-yr-old woman, with a previous history of low grade squamous intraepithelial lesion in the cervix, presented with heavy menstrual bleeding. At hysteroscopy, a fundal polyp was removed from the right cornu which displayed many glands lined by atypical, mitotically active epithelium with features characteristic of endocervical adenocarcinoma in situ (AIS) of intestinal subtype. Subsequent cervical liquid-based cytology and colposcopically directed biopsies revealed no causative lesion, but residual PreservCyt from the ThinPrep vial tested positive for high risk HPV type other than HPV 16 and 18. Further biopsies from the endocervical canal and base of the resected polyp showed intestinal type AIS, while all those from the intervening anterior and posterior endometrial lining exhibited normal endometrium only. Genomic DNA extracted from the endometrial polyp and second set of endocervical biopsies tested positive for HPV 31, an uncommon cause of endocervical glandular neoplasia. Endocervical AIS typically arises in the transformation zone but may be found exclusively in the endocervical canal and rarely as high as 30 mm from the ectocervix. Contiguous spread into the lower uterine segment is known to occur, as are proximate so-called skip lesions. However, finding a 'skip' lesion 80 mm from the transformation zone poses an interesting pathogenetic conundrum as well as a therapeutic dilemma in a young patient desirous of retaining fertility. Issues relating to pathogenesis include necessary metaplasia of the endometrial glandular epithelium to 'susceptible' endocervical type epithelium within the polyp or metastatic implantation of transformed endocervical glandular cells onto the polyp. The current management plan involves regular hysteroscopic surveillance of the uterine cavity.

Early acquisition of anogenital human papillomavirus among teenage men who have sex with men.

BACKGROUND: Anogenital human papillomavirus (HPV) is common among men who have sex with men (MSM) and causes anal cancer. This study examined the determinants of initial anogenital HPV infection among teenage MSM. METHODS: Two hundred MSM aged 16 to 20 years were recruited via community and other sources. Men were tested for HPV DNA from the anus and penis. RESULTS: The proportion of men with anal HPV of any type increased from 10.0% in men reporting no prior receptive anal sex to 47.3% in men reporting ≥ 4 receptive anal sex partners (P < .001).A similar pattern was also seen with HPV type 16 (P = .044). The proportion of men with penile HPV increased from 3.7% in men reporting no prior insertive anal sex to 14.8% in men reporting ≥ 4 insertive anal sex partners (P = .014). Overall, 39.0% (95% confidence interval (CI), 32.2%-46.1%) of men had at least 1 HPV type: 23.0% (95% CI, 17.4%-29.5%) had a vaccine-preventable type (6, 11, 16 or 18). CONCLUSIONS: Early and high per partner transmission of HPV occurred between men soon after their first sexual experiences. HPV vaccination needs to commence early for maximal prevention of HPV among MSM.

Improving oral human papillomavirus detection using toothbrush sampling in HIV-positive men who have sex with men.

Pre- and postabrasion oral rinse samples (ORS) and a toothbrush sample detected human papillomavirus (HPV) DNA in at least one sample among 45 (26%) of 173 HIV-positive men who have sex with men. There was moderate agreement for HPV genotype detection between the preabrasion and postabrasion ORS (κ = 0.49; 95% confidence interval [CI], 0.37 to 0.61). There was good agreement between postabrasion ORS and toothbrushes (κ = 0.70; 95% CI, 0.60 to 0.80). The sensitivities for HPV genotypes detected were 80% (95% CI, 69 to 88) for preabrasion ORS, 65% (95% CI, 54 to 76) for postabrasion ORS, and 75% (95% CI, 63 to 84) for toothbrushes.

Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea.

OBJECTIVE: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples. DESIGN: Exploratory observational study. SETTING: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea. PARTICIPANTS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal). PRIMARY AND SECONDARY OUTCOME MEASURES: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain. RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%). CONCLUSION: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.