AIDS Malignancy Consortium (AMC)

这项补充研究的父母拨款是肛门癌/HSIL结果研究(ANAR)研究，这是一项大型的多地点随机临床试验，是艾滋病恶性联盟(AMC)的协议，UM1CA121947。它旨在确定肛门高级别鳞状上皮内病变(HSIL)的识别和治疗是否在降低肛门癌发病率方面有效，类似于目前预防宫颈癌的方法。自20世纪70年代以来，肛门癌在普通人群中的男性和女性都有所增加。这在艾滋病毒携带者(PLWH)中尤其常见，尤其是与艾滋病毒携带者(MSMLWH)发生性行为的男性，其中目前的发病率超过每年100/100,000(1)。PLWH患肛门癌的风险很高，因为肛门HSIL及其病原体--肛门人乳头瘤病毒(HPV)感染的患病率、发病率和持久性都很高(2)。SARS-CoV-2大流行对这项研究的进行产生了戏剧性的影响，促使全国所有主要研究地点在2020年3月停止对随机参与者的筛选、登记和跟踪。预计这些活动将于2020年5月在一些地点恢复，随着时间的推移，越来越多的地点将恢复正常活动。然而，除了影响正常的研究活动外，SARS-CoV-2还可能通过影响肛门HPV感染的自然历史、肛门HSIL的发展和持续以及从HSIL向肛门癌的进展而产生额外的相关性。这是因为越来越多的证据表明，SARS-CoV-2病毒是从粪便中排出的，可能会感染胃肠道。目前尚不清楚SARSCoV-2是否能特异性地感染肛门上皮，是否影响肛门HPV感染的生物学，如何影响局部免疫反应，是否影响肛门HSIL的自然病程。此外，在肛门癌风险最高的人群PLWH中，对肛门感染SARS-CoV-2一无所知。该研究为着手解决这些问题提供了一个理想的机会，特别是因为该研究的参与者中有很高比例的人来自医疗服务不足的少数群体，他们也是感染SARS-CoV-2病毒的高风险人群。本补充资料的重点是描述从PLWH的肛拭子样本中检测到SARS-CoV-2，以进行锚定研究；检查其与筛查人群中普遍的肛门HPV感染和HSIL的关系；并通过检查其与HSIL消退和HPV感染清除的关系来确定其对肛门HPV感染和HSIL自然病史的影响。

The parent grant of this supplement is the ANal Cancer/HSIL Outcomes Research (ANCHOR) Study, a large multi-site randomized clinical trial and protocol of the AIDS Malignancy Consortium (AMC), UM1CA121947. It is designed to determine if identification and treatment of anal high-grade squamous intraepithelial lesions (HSIL), the anal cancer precursor, is effective in reducing the incidence of anal cancer, similar to the approach currently in place to prevent cervical cancer. Anal cancer has increasing in the general population in both men and women since the 1970s. It is particularly common among people living with HIV (PLWH) and especially men who have sex with men living with HIV (MSMLWH), among whom current incidence exceed 100/100,000 per year (1). PLWH are at high risk of developing anal cancer because of a high prevalence, incidence and rate of persistence of anal HSIL and the causative agent, anal human papillomavirus (HPV) infection (2). The SARS-CoV-2 pandemic has had a dramatic effect impact on the conduct of the study, prompting all ANCHOR study sites round the country to cease screening, enrollment and follow-up of randomized participants in March, 2020. Expectations are that these activities will resume at some sites in May, 2020 with more and more sites resuming normal activity over time. However, apart from affecting normal study activities, SARS-CoV-2 may have additional relevance by impacting on the natural history of anal HPV infection, development and persistence of anal HSIL, and progression from HSIL to anal cancer. This is because of the growing body of evidence that SARS-CoV-2 is shed in stool and may infect the gastrointestinal tract. Nothing is known at present as to whether SARSCoV-2 can infect the anal epithelium specifically, whether it affects the biology of anal HPV infection, how it affects the local immune response, and whether it affects the natural history of anal HSIL. Furthermore, nothing is known about anal SARS-CoV-2 infection in the group at highest risk of anal cancer, PLWH. The ANCHOR study offers an ideal opportunity to begin to address these issues particularly since a high proportion of participants in the ANCHOR Study are from medically underserved minority populations who are also at very high risk of SARS-CoV-2 infection. The focus of this supplement is to describe detection of SARS-CoV-2 in anal swab samples from PLWH being screened for the ANCHOR study; examine its relationship to prevalent anal HPV infection and HSIL in the screening population; and determine its effect on the natural history of anal HPV infection and HSIL by examining its relationship to regression of HSIL and clearance of HPV infection in the subset of enrolled participants randomized to the active monitoring arm.