Design and initial findings of a natural history study of anal HPV and associated lesions among young adult women in Costa Rica

Anal cancer is caused by HPV, and its incidence has increased globally over the last five decades. We conducted an anal HPV natural history study nested in the Costa Rica HPV Vaccine Trial (CVT) to quantitatively describe the natural history and clinical outcomes of anal HPV in HIV-negative women. CVT was a randomized clinical trial of the bivalent HPV vaccine, and an anal substudy included women selected based on a priori criteria to enrich for anal disease. For women in the anal substudy, anal samples were collected for cytology and determination of HPV16/18/45 for up to four annual visits. Women were referred for high-resolution anoscopy (HRA) based on abnormal anal cytology or anal HPV16/18/45 positivity. We describe the analytic cohort for this study according to inclusion criteria and factors associated with referral criteria for HRA during study follow-up. 9,416 women, 1,178 were included in the anal substudy (age-range = 23-35-years): 93 had prevalent anal HPV16, 236 had cervical HPV16, 364 had an anal high-risk HPV infection other than 16, 295 had anal low-risk HPV, and 227 were included as anal HPV-negative controls; 352 women were included because of a CIN3+ in study follow-up. From 3,033 study visits over a median of 70 months follow-up, 71 (6%) women were referred to HRA. This anal study nested within the CVT infrastructure and enriched for anal disease provides a unique setting to address research questions related to the natural history of anal HPV infections and associated lesions in women without HIV.