Screening Strategies Among High-Risk Populations for Anal Cancer

The incidence of anal cancer has nearly doubled over the past decades, along with increased advanced disease and mortality. Persistent high-risk human papillomavirus (hrHPV) infection leads to anal high-grade squamous intraepithelial lesion (aHSIL), the precursor to anal cancer. Anal cancer risk is also exceptionally high among individuals with chronic impairment of the immune system and women with an history of high-grade anogenital tract diseases. Early detection of aHSIL, particularly among high-risk populations, is crucial to reduce cancer incidence and disease burden. However, the current recommendation for aHSIL screening is based on expert opinions, and research is scarce. Therefore, we propose this large multisite study to investigate potential screening markers for aHSIL. It is crucial to develop reliable markers to stratify risks of aHSIL progression and regression. Given the importance of local DNA methylation and the immune environment to viral stimulus and carcinogenesis, we will examine DNA methylation and immunological profiles to identify markers for cancer risk stratification after aHSIL. Examining local immune responses may also shed light on targeted immunotherapeutic approaches and lead to better outcomes. Additionally, given the increasing incidence of anal cancer and poor outcomes due to late presentation we will examine additional environmental covariates to determine whether they play a pivotal role in aHSIL prevalence and clearance. We will recruit 500 men and women at high risk for anal cancer from Emory University and the University of Miami. We will follow them yearly for up to two years. Overall, the proposed study provides a unique opportunity to examine the much-needed evidence on early aHSIL screening among high-risk populations. The methylation results will be crucial to stratify risks of screen-detected aHSIL and could be translated to screening. The immune and inflammatory profile will identify alterations associated with neoplastic progression and subsequently inform targeted immune interventions for better outcomes.