High Grade Anal Dysplasia in People Living with HIV: A Review of the Anal Cancer/HSIL Outcomes Research (ANCHOR) Trial. Implications for Screening and Treatment Strategies to Minimize Anal Cancer in a Very High-risk Population

Abstract

The rates of AIDS-defining cancers have plummeted for people living with HIV (PLWH) and who have access to highly active antiretroviral therapies. In contrast, as survival of PLWH has improved and now rivals that of age-matched controls, rates of non-AIDS-defining cancers are increasing. Exposure to oncogenic viruses including human papillomavirus (HPV) as well as to traditional carcinogens, such as tobacco and alcohol are among the reasons for many of these cancers. Worldwide, anal cancer rates are increasing, and this is particularly true for high-grade squamous intraepithelial lesions (HSIL) evolving into invasive anal cancer in PLWH. Herein, I briefly review the oncogenic viruses most important in the pathogenesis of AIDS-defining and non-AIDS-defining malignancies and then focus on the link between HPV and anal cancer and efforts to minimize the risk of anal cancer in PLWH. The Anal Cancer/HSIL Outcomes Research (ANCHOR) study is a randomized phase III clinical trial which enrolled nearly 4500 participants across 25 diverse cities in the United States. PLWH who at time of enrollment were 35 years of age or older and who had biopsy-proven HSIL were eligible to take part in the study. The study is the first to show that screening and treating HSIL in a group at high risk for anal cancer can lead to a reduction in anal cancer incidence. Lessons learned from the ANCHOR study may also provide a blueprint for best practices when reaching out and recruiting marginalized groups with cancer into clinical trials. Much work is needed to plan for screening and treatment programs, including better algorithms for referral for high resolution anoscopy (HRA), and increased training to develop a workforce proficient in HRA screening and treatment of anal cancer. The development of progression biomarkers to identify those with HSIL most in need of treatment is essential. Finally, a more detailed analysis of costs and benefits of screen and treat algorithms for this malignancy is necessary for anal cancer screening to be implemented on a global scale.