Einstein/Rwanda DRC Consortium for Research in HIV/HPV Malignancies

摘要： 高危类型的人乳头瘤病毒（HPV）几乎会导致所有宫颈癌，大多数是肛门癌、外阴癌、阴道癌， 阴茎癌和口咽癌占很大比例。男男性行为者（MSM） 由于感染HPV的高危行为，以及艾滋病毒感染者患肛门癌的风险增加 （MSM-LWH），由于对HPV的免疫反应受损，肛门癌的风险最高。 了解肛门生殖器HPV感染和癌前病变的患病率和发病率及其 高危人群中的相关风险因素尤为重要，因为与大多数其他癌症不同，HPV- 相关的癌症是可以预防的。这些癌症的预防可以通过初级预防来实现。 预防（疫苗接种）或潜在地通过识别和治疗癌前病变 病变 一般来说，对肛门和阴茎HPV感染的患病率和发病率知之甚少， 肛门和阴茎鳞状上皮内病变（SIL）的MSM谁住在撒哈拉以南非洲（SSA）。我们 之前完成了一项关于卢旺达MSM中HPV的研究，并意外地发现了一个意想不到的低患病率 肛门HPV感染率在MSM-LWH和HIV未感染（HIV[-]）MSM之间无差异。 我们建议继续我们的调查肛门和阴茎HPV在男男性接触者进行补充， 研究生活在刚果民主共和国（DRC）的男男性接触者。我们假设刚果的男男性接触者 由于文化和性别差异， 实践这项拟议的研究旨在提供肛门和阴茎的患病率和发病率的数据， HPV感染和HPV相关病变在这些解剖部位，并描述相关的危险因素， 刚果男男性接触者，并将这些结果与我们之前在卢旺达的男男性接触者研究结果进行比较。 在进行形成性研究以接触目标男男性行为者群体并建立地方能力， 在刚果民主共和国进行拟议的研究，我们将招募并随访300名刚果男男性接触者，150名男男性接触者-LWH和 150名HIV阴性的MSM，每6个月一次，持续18个月，就像我们在卢旺达研究的前18个月所做的那样。 此外，我们将把对卢旺达男男性接触者队列的随访延长两年， 癌前病变的发生率。我们将使用低成本，强大的HPV来测量当前的HPV感染。 我们已经在卢旺达引入了基因分型系统，作为这笔赠款的一部分， 通过测量血液中循环的抗HPV抗体来检测刚果民主共和国和过去的暴露情况。我们还将测量 肛门微生物组，以确定某些微生物环境是否影响肛门HPV自然史 就像宫颈HPV一样。 我们的（长期）目标是在这两个国家建立一个男男性接触者队列，研究男男性接触者的自然史。 生活在SSA的MSM的肛门和阴茎HPV。这一贡献意义重大，因为它将确定 暴露于HPV和在什么年龄，这可以用来指导政策，什么年龄的目标男男性接触者 预防性HPV疫苗。拟议的研究是创新的，因为它利用和扩大了当地的 卢旺达和刚果民主共和国的研究和医疗能力，并建立南南合作， 肛门和阴茎HPV和相关异常的最新自然史及其相应风险 因素，这是描述不佳的男男性接触者-LWH和艾滋病毒[-]男男性接触者生活在SSA。

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.