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

摘要： 人乳头瘤病毒(HPV)的高危类型导致几乎所有的宫颈癌，大多数是肛门，外阴，阴道， 和阴茎癌，以及口咽癌的相当大比例。男男性行为者(MSM)是 由于感染HPV的高危行为和艾滋病毒携带者，患肛门癌的风险增加 (MSM-LWH)是患肛门癌的最高风险人群，因为他们对HPV的免疫反应也受到损害。 了解肛门生殖道HPV感染和癌前病变的患病率和发病率及其影响因素 高危人群中的相关风险因素尤其重要，因为与大多数其他癌症不同，HPV- 相关癌症很可能是可以预防的。这些癌症的预防可以通过初级保健来完成。 预防(接种疫苗)或可能通过识别和治疗癌前病变进行二级预防 损伤。 总体而言，人们对肛门和阴茎HPV感染的流行和发病率知之甚少。 生活在撒哈拉以南非洲(SSA)的男男性接触者的肛门和阴茎鳞状上皮内病变(SIL)。我们 之前完成了对卢旺达MSM中HPV的研究，令人惊讶地发现感染率出人意料地低 男男性接触者与非HIV感染(HIV[-])男男性接触者肛门HPV感染率无差异。 我们建议通过进行补充研究来继续我们对男男性接触者肛门和阴茎HPV的研究。 对生活在刚果民主共和国(DRC)的男男性接触者进行研究。我们假设刚果男男性接触者是 由于不同的文化和性别，可能比卢旺达男性有更高的艾滋病毒感染率 练习。这项拟议的研究旨在提供有关肛门和阴茎患病率和发病率的数据。 这些解剖部位的HPV感染和HPV相关病变，并描述与 刚果男男性接触者，并将这些发现与我们之前在卢旺达进行的男男性接触者研究的结果进行比较。 在进行形成性研究以接触到目标男男性接触者人群并建立当地能力以 在刚果民主共和国进行拟议的研究，我们将招募和跟踪300名刚果男男性接触者，150名男男性接触者-LWH和 150名HIV[-]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，我们将把我们对卢旺达男男性接触者队列的后续行动再延长两年，以进行评估 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 我们已经引入卢旺达的基因分型系统，并将作为这笔赠款的一部分，引入 通过测量血液中循环的抗HPV抗体来检测DRC和过去的暴露情况。我们还将测量 确定某些微生物环境是否影响肛门HPV自然病史的肛门微生物组 就像他们对宫颈HPV所做的那样。 我们的(长期)目标是在两国建立一个男男性接触者队列，以研究 SSA地区男男性接触者的肛门和阴茎HPV感染这一贡献意义重大，因为它将确立 暴露于HPV以及在什么年龄，这可以用来指导针对MSM目标年龄的政策 预防性接种HPV疫苗。拟议的研究具有创新性，因为它利用并扩展了当地的 在卢旺达和刚果民主共和国的研究和医疗能力，并建立了南南合作，以开展 肛门和阴茎HPV及其相关异常的最新自然病史及其相应的风险 因素，这在生活在SSA的MSM-LWH和HIV[-]MSM中描述得很差。

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.