7. Project Summary / Abstract The ANCHOR Study is an ongoing, longitudinal, multicenter trial in people living with HIV (PLWH), which demonstrated that treating anal high-grade squamous intraepithelial lesions (HSIL, or precancer) prevents progression to anal cancer, as compared to active monitoring (six-monthly high-resolution anoscopy exams with biopsies and cytology). This trial was a unique opportunity to conduct a randomized study comparing monitoring to treatment, the utility of which had not yet been established as effective and therefore not considered standard care. As part of the trial, we collected serial samples to establish a biobank, and therefore a unique opportunity to conduct comparisons in participants who did and did not progress to cancer. Our aims with this supplement are to initiate the trial’s correlative science objectives to inform HSIL screening algorithms for secondary prevention of anal cancer, optimize use of HRA and HSIL treatment resources by identifying biomarkers of HSIL regression, and explore the molecular pathogenesis of progression from HSIL to anal cancer. Findings from this research, among other assays, are intended to inform optimal screening and treatment strategies for anal cancer prevention in PLWH and potentially other groups.