Abstract: High-risk types of human papillomavirus (HPV) cause virtually all cervical cancer, most anal, vulvar, vaginal, and penile cancer, and a significant proportion of oropharyngeal cancer. Men who have sex with men (MSM) are at an elevated risk of anal cancer because of high-risk behaviors for acquiring HPV, and those living with HIV (MSM-LWH), are at the highest risk of anal cancer due to also having an impaired immune response to HPV. Understanding the prevalence and incidence of anogenital HPV infection and precancerous lesions and their associated risk factors in at-risk populations is particularly important since, unlike most other cancers, HPV- related cancers are likely preventable. Prevention of these cancers may be accomplished through primary prevention (vaccination) or potentially through secondary prevention by identifying and treating precancerous lesions. In general, little is known about the prevalence and incidence of anal and penile HPV infection, and anal and penile squamous intraepithelial lesions (SIL) among MSM who live in sub-Saharan Africa (SSA). We previously completed a study of HPV in Rwandan MSM and surprisingly found an unexpected low prevalence of anal HPV and no difference in anal HPV prevalence between MSM-LWH and HIV-uninfected (HIV[-]) MSM. We propose to continue our investigations of anal and penile HPV in MSM by conducting a complementary study in MSM living in the Democratic Republic of Congo (DRC). We hypothesize that Congolese MSM are likely to have higher hrHIV prevalence than do Rwandan men because of different cultural and sexual practices. The proposed study is designed to provide data on the prevalence and incidence of anal and penile HPV infection and HPV-associated lesions at these anatomic sites, and to describe associated risk factors for Congolese MSM, and compare these findings to those in our prior MSM study in Rwanda. After conducting formative research to reach the target MSM population and build local capacity to conduct the proposed research in DRC, we will enroll and follow 300 Congolese MSM, 150 MSM-LWH and 150 HIV[-] MSM, every 6 months for 18 months, as we did for the first 18 months of our Rwanda study. Moreover, we will extend our follow-up of the Rwandan MSM cohort to for two additional years to assess incidence of precancerous lesions. We will measure current HPV infections using a low-cost, robust HPV genotyping system that we have already introduced into Rwanda and will, as part of this grant, introduce into DRC, and past exposures by measuring anti-HPV antibodies circulating in the blood. We will also measure the anal microbiome to determine whether certain microbiotic environments influence the anal HPV natural history as they seem to for cervical HPV. Our (long-term) goal is to establish a cohort of MSM in both countries to study the natural history of anal and penile HPV in MSM living in SSA. This contribution is significant as it will establish the extent of exposure to HPV and at what ages, which can be used to guide policy on what age to target MSM for prophylactic HPV vaccination. The proposed research is innovative as it leverages and expands the local research and medical capacity in Rwanda and DRC, and creates a south-south collaboration, to conduct a state-of-the-art natural history of anal and penile HPV and related abnormalities, and their corresponding risk factors, which is poorly described in MSM-LWH and HIV[-] MSM living in SSA.

PROJECT NARRATIVE This project is to conduct a prospective study in the Democratic Republic, and continue one in Rwanda, of anal and penile high-risk HPV in men who have sex with men (MSM) with and without human immunodeficiency virus (HIV) infection. The primary goal of the study is to compare and contrast the natural history of anal and penile HPV and related abnormalities, as well as the associated risk factors, in MSM from the two countries. The propose project will provide important knowledge on exposure to HPV and cancer risks in these populations and inform policy on if and what age to vaccinate these high-risk populations.