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

## TL;DR

This study tracks anal HPV infections in young women in Costa Rica to understand their natural history and improve cancer screening strategies.

## Contribution

The study provides new insights into anal HPV infection progression and screening in HIV-negative women through a large, longitudinal substudy.

## Key findings

- 1,178 women were followed over 3,033 visits, with 71 referred for high-resolution anoscopy.
- The study cohort was enriched for anal disease, including prevalent and incident high-risk HPV infections.
- Findings will help inform anal cancer screening guidelines for HIV-negative women.

## Abstract

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.

Infection with human papillomavirus (HPV) is the primary cause of anal cancer, for which the majority of cases occur in women. Anal cancer screening guidelines have limited evidence to inform effective strategies for women with HIV. We designed a study that was nested within the Costa Rica HPV Vaccine Trial to understand the natural history of anal HPV infection and referred high‐risk women to receive high‐resolution anoscopy (HRA). From 10,302 women in CVT, we followed 1,178 women over 3,033 annual visits and referred 71 to HRA. These findings will inform our understanding of the natural history of anal HPV infection and inform guidelines for anal cancer screening programs.