Oral HPV Research Among Latin Americans Living with HIV (ORAL - H² Study)

ABSTRACT Oropharyngeal cancer (OPC) is predominantly caused by HPV 16 and other oncogenic HPV types and disproportionately impacts men and people living with HIV (PLWH). There is no reliable method to detect OPC pre-cancerous lesions for secondary prevention. Trials assessing efficacy of the 9vHPV vaccine to prevent OPC are ongoing by our team: NCI-funded U54 grant, Research on Oral and Cervical Cancer, HPV and HIV in the Americas [ROCCHHA] Trial 201 among men with HIV, and the Merck v503-049 trial among HIV-uninfected men. While HPV vaccination is a promising approach for the primary prevention of OPC, vaccination may not be available to those in greatest need as most countries exclude males in their national programs and may not have policies for PLWH vaccination. Additional methods to prevent OPC and identify PLWH at highest risk for surveillance are urgently needed, particularly given that OPC incidence rates are significantly increasing in the US and Latin America. To inform prevention strategies, the identification of modifiable risk factors and easily measured biomarkers identifying those at highest risk is needed. Development of HPV-related OPC is multi- factorial. Sexual behavior leading to an oral oncogenic HPV infection is a necessary step. Regardless of anatomic site of infection, only a proportion of infections persist and progress to cancer. Multiple interplaying factors influence viral persistence. We are among the few groups that have conducted large oral HPV natural history studies contributing to this literature. Results from ours and other studies indicate that older age, poor oral health, immune dysregulation, such as occurs among PLWH, and aberrant DNA methylation influence oral HPV persistence. Exacerbating this is the fact that PLWH are living to older ages which results in lifelong immune dysfunction that may accelerate biological aging, increase risk of acquiring or reactivating a multitude of infections such as EBV, and ultimately lead to reduced oncogenic viral control. Social factors compound this scenario as PLWH have lower utilization of dental care and other services resulting in prolonged untreated oral infections, subsequent chronic oral inflammation, periodontal disease, and tooth loss, factors that potentially promote oral HPV carcinogenesis, and have independently been associated with HPV-OPC risk. We are conducting two large studies as part of our ROCCHHA grant among PLWH that obtain clinical data and oral gargle specimens at bi-annual study visits, which we will leverage to study oral HPV natural history. The goal of this application is to define the natural history of oncogenic oral HPV infection among PLWH. The central hypothesis of the Oral HPV Research Among Latin Americans Living with HIV (ORAL H2) Study is that among PLWH advanced biological age, dental health, and viral factors are associated with persistent oral oncogenic HPV. We will estimate oral HPV 16 and oncogenic HPV infection, assess factors associated with viral persistence, and determine the optimal combination of biomarkers and behavioral factors that predict oral oncogenic HPV persistence.