Persistent anal human papillomavirus (HPV) infection is the primary cause of anal cancer which is a common cancer among men having sex with men (MSM). Annual anal cancer screening is standard of care for HIV+ MSM and recommended by expert opinion for HIV- MSM; thus, Pap cytology and high-resolution anoscopy (HRA) are now increasingly offered by clinics. But most HIV+ and HIV- MSM do not screen. Since home-based self-sampling increases rates of cervical cancer screening and self-sampling is acceptable to MSM, it is im- portant to investigate home-based screening for anal cancer among MSM. No one has assessed compliance with annual home-based anal canal self-sampling which is required to detect persistent HPV infections among MSM. Current anal cancer screening protocols already mirror cervical cancer screening protocols with in- creased reliance on a molecular biomarker (e.g., HPV DNA testing). DNA collection works well with home- based kits, but one-time DNA screening is of no value for MSM given their high HPV prevalence; thus, an ex- periment of repeated DNA screening can efficiently test important questions: Will MSM comply with annual bi- omarker screening? Will home-based sampling increase compliance? What other factors are associated with repeated annual screening? And, what proportion of men will agree to clinic-based HRA-directed biopsy (the definitive test for precancerous lesions) after home-based self-sampling? Our long-term goal is to reduce mor- bidity and mortality from anal cancer given increasing incidence of disease. Using a 2-arm randomized con- trolled trial, our primary objective is to determine compliance with annual DNA-based screening among Hou- ston HIV+ and HIV- MSM, aged ?27 years. Men randomized to arm 1 will receive an HPV DNA home-based collection kit in the mail at 0 and 12 months and those in arm 2 will attend a clinic where a clinician will collect the DNA specimen at 0 and 12 months. Then, men will receive HRA-directed biopsy to assess precancerous lesions by study arm. We will recruit a total of 400 men, with oversampling of African American and Latino men. We hypothesize that a majority of men will comply with annual screening with increased compliance among men in the home-based arm vs clinic-based arm. We will test our hypothesis with 3 specific aims: 1. Determine men?s compliance with annual anal HPV DNA specimen collection; 2. Determine factors associated with annual screening compliance; 3. Establish the proportion of men in each arm who agree to have HRA. The current research will deliver: 1) The first estimates of compliance with an annual bi- omarker screening program among MSM; 2) The first estimates of the relative ability of home-based screening to increase annual compliance; and 3) Evidence of the influence that home-based vs clinic-based screening has on uptake of HRA-directed biopsy. The proposed research could indicate that annual HPV DNA testing may identify at-risk MSM who then agree to follow up with HRA; thus, we will determine how high-risk men are identified for treatment in light of very limited screening resources.