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

爱因斯坦/卢旺达刚果民主共和国 HIV/HPV 恶性肿瘤研究联盟

基本信息

批准号：
10084655
负责人：
Kathryn M. Anastos
金额：
$ 25.88万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-21 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10084655
关键词：
AIDS related cancer Africa South of the Sahara Age Anal canal Anatomy Anogenital Human Papilloma Virus Infection Antibodies Anus Area Blood Central Africa Cervical Cessation of life Collaborations Colorectal Cancer Country Data Democratic Republic of the Congo Developed Countries Development Disease Enrollment Environment Exposure to Gastrointestinal tract structure General Population Genotype Goals Grant HIV HIV Infections HPV-High Risk Human Papilloma Virus Vaccination Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Immune response Impairment Incidence Individual Inflammatory Bowel Diseases Investigation Knowledge Lesion Link Low Prevalence Malignant Neoplasms Malignant Vaginal Neoplasm Malignant neoplasm of anus Malignant neoplasm of cervix uteri Malignant neoplasm of penis Malignant neoplasm of vulva Measures Medical Natural History Pathogenesis Persons Policies Population Populations at Risk Prevalence Prevention strategy Primary Prevention Prospective Studies Research Resolution Risk Risk Factors Rwanda Secondary Prevention Source Squamous intraepithelial lesion System Time Vaccinated Vaccination Virus Diseases cancer prevention cancer risk cohort cost design dysbiosis follow-up high risk high risk behavior high risk men high risk population infection rate infection risk innovation malignant oropharynx neoplasm men men who have sex with men microbial microbial community microbiome normal microbiota penis premalignant prophylactic virtual

项目摘要

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.

抽象的：高危型人乳头瘤病毒 (HPV) 几乎可导致所有宫颈癌、大多数肛门癌、外阴癌、阴道癌、和阴茎癌，以及很大比例的口咽癌。男男性行为者 (MSM) 是由于感染 HPV 的高危行为以及艾滋病毒感染者，患肛门癌的风险较高（MSM-LWH）由于对 HPV 的免疫反应受损，因此患肛门癌的风险最高。了解肛门生殖器HPV感染和癌前病变的患病率和发生率及其影响高危人群中的相关危险因素尤为重要，因为与大多数其他癌症不同，HPV- 相关癌症可能是可以预防的。这些癌症的预防可以通过初级预防来实现预防（疫苗接种）或可能通过识别和治疗癌前病变进行二级预防病变。一般来说，人们对肛门和阴茎 HPV 感染的流行率和发病率知之甚少，生活在撒哈拉以南非洲 (SSA) 的 MSM 中的肛门和阴茎鳞状上皮内病变 (SIL)。我们之前在卢旺达 MSM 中完成了一项 HPV 研究，令人惊讶地发现了意想不到的低患病率 MSM-LWH 和未感染 HIV (HIV[-]) MSM 之间的肛门 HPV 患病率没有差异。我们建议通过开展补充性研究，继续对 MSM 中的肛门和阴茎 HPV 进行研究。研究居住在刚果民主共和国 (DRC) 的 MSM。我们假设刚果 MSM 是由于不同的文化和性别，艾滋病毒感染率可能高于卢旺达男性做法。拟议的研究旨在提供有关肛门和阴茎的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，并描述相关的危险因素刚果 MSM，并将这些发现与我们之前在卢旺达进行的 MSM 研究进行比较。在进行形成性研究以达到目标 MSM 人群并建立当地能力后在刚果民主共和国进行拟议的研究，我们将招募并跟踪 300 名刚果 MSM、150 名 MSM-LWH 和 150 名 HIV[-] MSM，每 6 个月一次，持续 18 个月，正如我们在卢旺达研究的前 18 个月所做的那样。此外，我们将对卢旺达 MSM 队列的随访时间再延长两年，以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 感染我们已经将基因分型系统引入卢旺达，并将作为这笔赠款的一部分引入 DRC，通过测量血液中循环的抗 HPV 抗体来确定过去的暴露情况。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 自然史因为它们似乎针对宫颈 HPV。我们的（长期）目标是在两国建立一批 MSM，以研究 MSM 的自然史居住在 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 以及在什么年龄，这可用于指导针对 MSM 的目标年龄的政策预防性 HPV 疫苗接种。拟议的研究具有创新性，因为它利用并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，开展最先进的肛门和阴茎 HPV 自然史及相关异常及其相应风险这些因素在生活在 SSA 的 MSM-LWH 和 HIV[-] MSM 中描述得很少。