Prevalence of Anal Human Papillomavirus Infection and Anal High-Grade Squamous Intraepithelial Lesions Among Men Who Have Sex With Men 50 Years and Older Living With or Without HIV.

BACKGROUND: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). SETTING: We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. METHODS: One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. RESULTS: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. CONCLUSION: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

"The problem is that our culture is just so messed up about aging." Recruiting older men who have sex with men (MSM) into research studies: an example from a study of aging, HIV, and anal HPV.

BACKGROUND: Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research. METHODS: We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50-75. RESULTS: We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered "older" in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care. CONCLUSION: Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.

Rationale and design of the Anal HPV, HIV and Aging (AHHA) study: Protocol for a prospective study of anal HPV infection and HSIL among men who have sex (MSM) or trans women living with and without HIV, ages 50 and older.

Introduction: More than half of people living with HIV in the US are 50+ years old. Despite the benefits of antiretroviral therapy, older individuals with HIV are at higher risk for illnesses than their HIV-negative counterparts. Anal cancer, anal high-grade squamous intraepithelial lesions (HSIL), and anal HPV-16 infection occur most frequently among men who have sex with men living with HIV (MSMLWH). Men aged 60+ are 3-fold more likely to be diagnosed with anal cancer compared with younger men. Despite the increasing risk of anal cancer with age and HIV, little is known about the relationships among aging, HPV infection, HSIL and HIV. Methods and analysis: The Anal HPV, HIV, and Aging (AHHA) Study is a two-stage project to evaluate the relationships among anal HPV infection, HSIL, HIV infection, and biomarkers of biological aging in MSM or trans women over the age of 50 years. Stage 1 will estimate the cross-sectional prevalence of both anal HPV infection and HSIL, based on outcomes of anal HPV DNA testing, and high-resolution anoscopy with biopsy. We will also study associations with study outcomes and serological biomarkers of inflammation (interleukin-6, C-reactive protein, D-dimer) and with the Veterans Aging Cohort Study Index and the Fried Frailty Phenotype using multivariable models. Participants living with HIV (n = 150) and HIV-negative participants (n = 150) will be enrolled. The 3-year Stage 2 longitudinal sample restricted to HSIL-negative and anal HPV-16 DNA-negative participants will estimate the 3-year incidence of both anal HSIL and anal HPV, stratified by HIV status through Cox proportional hazards regression. The effect of biomarkers of inflammation and markers of aging on study outcomes will be evaluated through multivariable repeated measures models stratified by HIV status. Ethics and dissemination: This protocol was approved by the University of California, San Francisco Institutional Review Board (IRB: 16-18966). Results will be disseminated through presentations at national/international scientific conferences and publication in peer-reviewed journals.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Prevalence of oral human papillomavirus infection among Indian HIV-positive men who have sex with men: a cross-sectional study.

BACKGROUND: Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population. METHODS: We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of oral HPV was 23.7% (95% CI: 19-29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4-6.9]) in multivariable analyses. CONCLUSIONS: This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

Genital Human Papillomavirus Infection in Indian HIV-Seropositive Men Who Have Sex With Men.

BACKGROUND: The incidence of penile cancer in Indian men is high. Little is known about genital human papillomavirus (HPV) infection in Indian HIV-seropositive men who have sex with men (MSM), a population that may be at particularly high risk for genital HPV infection and, potentially, penile cancer. In this study, we assessed the prevalence and risk factors for genital HPV infection in this population. DESIGN AND METHODS: Three hundred HIV-seropositive MSM were recruited from 2 clinical sites in India. They were tested for genital HPV infection using L1 HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. Participants received an interviewer-administered questionnaire that included questions on demographics and behaviors. RESULTS: Human papillomavirus data were available from 299 participants. The prevalence of any HPV type in the penis and scrotum was 55% and 54%, respectively. Human papillomavirus type 35 was the most common oncogenic HPV type followed by HPV-16. In multivariate analysis, being the insertive partner with 100+ male partners increased the odds of any penile HPV infection compared with not being insertive with any partners (odds ratio, 2.5; 95% confidence interval, 1.3-5.1). Circumcision was protective against penile HPV infection (odds ratio, 0.39; 95% confidence interval, 0.19-0.76). CONCLUSIONS: The prevalence of penile and scrotal HPV infection was high among Indian HIV-seropositive MSM. The most common oncogenic HPV type in this population, HPV-35, is not included in any currently available HPV vaccines. Insertive anal sex with men and lack of circumcision were the primary risk factors for penile HPV infection in this population.

Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India.

BACKGROUND: India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. METHODS: We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. CONCLUSIONS: Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.

Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM.

OBJECTIVE: HIV-positive MSM are at increased risk of anal human papillomavirus (HPV) infection compared with men in the general population, and little is known about the natural history of anal HPV infection in this population. The objective of this study was to determine the incidence of and risk factors for anal type-specific HPV infection. DESIGN: Prospective cohort study. METHODS: HIV-positive MSM were evaluated for anal HPV DNA, lifestyle factors, and sexual risk behaviors every 6 months for at least 2 years. RESULTS: The overall incidence rate of detectable type-specific anal HPV infection was 21.3 per 100 person-years [95% confidence interval (CI) 17.7-25.4] and was 13.3/100 person-years (10.5-16.6) for oncogenic HPV types. The most common incident infections were HPV 18 (3.7/100 person-years) and HPV 16 (3.5/100 person-years). An increased number of recent partners with whom the participant was the receptive partner [odds ratio (OR) 2.9 (1.6-5.1) 8+ partners vs. 0-1], an increased number of new partners in which the participant was the receptive partner [OR 1.03 (1.01-1.1) per partner], an increased number of new oral-anal contact partners in which the participant was the receptive partner [OR 1.1 (1.03-1.1) per partner], and the frequency of receptive anal intercourse [OR 1.1 (1.03-1.1) per act] all significantly increased the odds of incident HPV infection (P ≤ 0.05). CONCLUSION: HIV-positive MSM have a high incidence of oncogenic anal HPV infection. Recent receptive anal sexual behaviors, including receptive anal intercourse and receptive oral-anal contact, are the most important risk factors for incident anal HPV infection.

Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco.

BACKGROUND: HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, the risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. DESIGN: Cross-sectional data from the baseline visit of a 4-year prospective cohort study. METHODS: Three hundred forty-eight HIV-positive MSM were recruited in San Francisco, and they received a detailed sexual behavior risk factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA polymerase chain reaction. We used log-binomial multivariable models to determine the risk factors for anal HPV 16 infection. RESULTS: Ninety-two percent of HIV-positive MSM had at least 1 anal HPV type, 80% had at least 1 oncogenic HPV type, and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (relative risk: 1.6, 95% confidence interval 1.1 to 2.4, P = 0.01) for 201-1000 partners compared with 1-200. Injection drug use was independently associated with anal HPV 16 infection (relative risk: 1.5, 95% confidence interval 1.2 to 1.9, P = 0.003). CONCLUSIONS: The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and injection drug use.

Injection drug use in Rural Iran: integrating HIV prevention into iran's rural primary health care system.

Major opium trafficking routes traverse rural Iran, but patterns of drug use and HIV infection in these areas are unknown. In 2004, Iran's Ministry of Health integrated substance use treatment and HIV prevention into the rural primary health care system. Active opium or heroin users (N = 478) were enrolled in a rural clinic. Participants received counseling for abstinence from substances, or daily needle exchange and condoms. On enrollment, 108 (23%) reported injecting; of these, 79 (73%) reported sharing needles. Of 65 participants tested for HIV, 46 (72%) tested positive. Participants who received daily needle exchange/condoms stayed in the program longer than those who did not (AOR 2.08, 95% CI 1.1-3.88). This project demonstrates that HIV risks exist in rural Iran and suggests the innovative use of Iran's rural health care system to extend prevention and treatment services to these populations.