Abstract 2264: Co-infection with Epstein-Barr virus impacts oral HPV persistence
Authors: Dickey Brittney L. , Giuliano Anna R. , Sirak Bradley , Abrahamsen Martha , Lazcano-Ponce Eduardo , Villa Luisa L. , Coghill Anna E. 
Published: June 2022

Abstract
Rates of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) infection are increasing in men. The obligate precursor to OPC is a persistent infection with an oncogenic HPV type that is unable to be cleared via natural immunity alone. However, the factors that influence HPV persistence at the oral cavity are unknown. It is plausible that long-term infection with other pathogens at the same anatomic site indicates an overall inability to clear an oral infection. Epstein-Barr virus (EBV) is a saliva-transmitted gamma herpesvirus that infects 90% of the population by adulthood and replicates in the epithelial cells of the oropharynx. This study aimed to investigate whether oral EBV shedding, a marker of active viral replication, could serve as a biomarker for persistent, oncogenic oral HPV infection in men. Men with an HPV16 or 18 oral infection present at the baseline visit of the HPV Infection in Men (HIM) Study were included (n=63). Briefly, men from Tampa, FL, U.S.; Cuernavaca, Mexico; and Sao Paolo, Brazil were followed every 6 months for a median of 4.1 years. Men completed a risk factor questionnaire and provided an oral gargle sample at each visit. For this study, the baseline, 6-month, and 12-month oral specimens were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 system. Presence of EBV was evaluated in the baseline specimen using PCR to amplify and quantify the EBV DNA on the Rotor-Gene Q MDx instrument. Men with the same oral HPV type present at the 6-month and 12-month visit were categorized as 6-month and 12-month oral HPV persistent, respectively. The association between EBV and persistent HPV infection was investigated using a logistic regression model adjusted for age, country, and smoking. Among 63 men with oral HPV 16/18 infection at baseline, 44 HPV infections did not persist, 19 persisted to at least 6-months and 11 persisted to at least 12 months. Among the total sample, 32 also had EBV detected in the oral gargle at baseline. Among men who did not have a persistent HPV infection, 21 (47.7%) had EBV detected at baseline while 11 (57.9%) men with an HPV infection that persisted at least 6 months had detectable EBV at baseline; and 9 (81.8%) of the men who persisted to 12 months had EBV detected. Mean EBV viral load was highest among men who persisted to at least 12 months (5.0 log copies/ml) and was significantly higher than men who did not persist (2.5 log copies/ml; p=0.047). Detection of oral EBV at baseline was significantly associated with elevated risk of ≥12-month oral HPV 16/18 persistence (aOR: 9.90; 95% CI: 1.38-70.96), but not ≥6-month HPV 16/18 persistence (aOR: 1.62; 95% CI: 0.52-5.06).These data support the hypothesis that EBV reactivation may be a biomarker of poor immune control leading to increased risk of oral HPV persistence. The use of a biomarker that identifies men whose HPV infection may persist would be a useful tool to allow for screening and early detection of OPC.
Citation Format: Brittney L. Dickey, Anna R. Giuliano, Bradley Sirak, Martha Abrahamsen, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna E. Coghill. Co-infection with Epstein-Barr virus impacts oral HPV persistence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2264.