Evaluating immunity to oral human papillomavirus to understand the lower oropharyngeal cancer risk among MSM

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Project Abstract Oral human papillomavirus (HPV) is associated with 60-70% of oropharyngeal cancers (OPC), which are highly preventable with vaccination prior to HPV exposure. Men who have sex with men (MSM) living with HIV are at high risk for HPV, but they have a paradoxically low risk of OPC. It is hypothesized that repeated mucosal exposures to HPV in the anal canal generates protective antibody responses, potentially preventing oral HPV acquisition and persistence, resulting in a lower risk of OPC. It remains unclear whether site-specific exposures contribute to systemic immunity and whether systemic immunity is correlated with differential expression of HPV DNA between mucosal sites. The objective of this proposal is to test whether HPV-specific antibodies are associated with oral and rectal mucosal exposures and whether type-specific immunity induced by oral and rectal exposures protect the oral cavity from detectable HPV DNA. We are leveraging archived samples collected cross-sectionally from 620 participants from a well characterized cohort (TRUST/RV368) of MSM and transgender women in Nigeria to disentangle the interactions between mucosal site exposures, systemic immunity, and oral HPV DNA detection. To achieve this goal, we address the following specific aims: AIM 1: Quantify HPV type-specific immunity in relationship to mucosal exposure (penile, rectal, both oral and rectal) indexed to self-reported sexual behavior; AIM 2: Compare the concordance between type-specific serum antibodies with type-specific DNA detection in the oral cavity and anal canal. Findings will yield information on type-specific immunity in the oral cavity and whether it has a differential effect on detection of HPV DNA by mucosal site. With the oral cavity being an uncharacterized site of HPV modulation, our research is key to the development of therapies that control oral HPV and prevent OPC.