AIDS Malignancy Consortium (AMC)

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.