Characterize longitudinal events of oral high-risk human papillomavirus to alter risk for oropharyngeal cancer (CLEAR)

University Of Maryland Baltimore, Baltimore MD

Investigators

Abstract

Modified Project Summary/Abstract Section HIV is associated with a 2- to 5-fold higher risk of developing human papillomavirus-related oropharyngeal cancer (HPV-OPC), with up to 90% of cases attributed to oral high-risk (oHR)-HPV16. Because precancerous lesions are a challenge to diagnose, effective clinical interventions will require a thorough understanding of the natural history of oHR-HPV. The presence of persistent non-oral HR-HPV precedes precancerous lesion development in other HPV-related cancers; the same may be true for oHR-HPV. HIV and antiretroviral therapy (ART) may alter the oral microbiome and give rise to oral lesions and periodontal disease, creating an immune microenvironment conducive to persistent oHR-HPV that ultimately increases the risk for HPV-OPC. Predictors of oHR-HPV infection and persistence could serve as detection markers for HPV-OPC to prompt preventive treatment early in disease progression when treatment outcomes are most favorable. We propose to conduct a prospective study to characterize longitudinal events of oHR-HPV to alter risk for oropharyngeal cancer (CLEAR). We will screen a total of 1,200 HPV-unvaccinated individuals who are at highest risk for oropharyngeal cancer. A subset of 500 individuals, including those with a prevalent oHR-HPV will be followed every 6 months for up to 18 months. We will collect oral gargle and blood samples to detect incident and persistent oHR-HPV infection; measure CD4, HIV viral load, and the oral microbiome; characterize oral exposures; and perform dental examinations to document periodontal disease, oral lesions, and dental caries. We will determine the association between HIV clinical markers and oral exposures and the prevalence of oHR-HPV (AIM 1). We will compare the time course of oHR-HPV as a function of HIV status (AIM 2). We will evaluate the relationship between dental phenotypes, the oral microbiome, HIV clinical measures, and oHR- HPV infection (AIM 3). Understanding the oHR-HPV burden, time course of infection, and oral cavity indicators of the immune microenvironment in the context of HIV will generate robust data needed to help inform predictive models and develop rational risk-stratified screening algorithms to help mitigate risk of HPV-OPC.