Background
Most people acquire Epstein–Barr virus (EBV) and certain human papillomaviruses (HPVs) during their lifetime. HPV-related oropharyngeal carcinomas have increased in recent decades, particularly among men. The role of coinfection with viruses like EBV on HPV outcomes is unclear. We investigated potential associations between EBV serology and longitudinal outcomes of oral HPV infections in men.

Methods
This study included 119 men from the Finnish Family HPV Study who were followed up for 3 years. Blood and oral cavity samples were collected at baseline, 12-, 24-, and 36-month follow-up visits. HPV was genotyped with the Multimetrix assay, and the serum IgG antibodies of EBV proteins Zebra, EA-D, EBNA, and VCAp18 were measured with fluorescent bead-based multiplex serology. Univariate regression analysis was used to measure the strength of the association between different variables.

Results
Most participants (99.2%; n = 118) were EBV-seropositive with stable antibody titers throughout the follow-up. Self-reported history of atopy was positively associated with elevated EBNA-1 levels, with OR 7.43 (95% CI: 1.39–39.76). EBV seropositivity with high titers and elevated EA-D levels alone increased the risk of type-specific oral HPV persistence for Types 16, 18, 33, and 51, with OR 4.20 (95% CI: 1.09–16.19) and OR 6.23 (95% CI: 1.19–32.75), respectively.

Conclusions
Most of the participants were EBV-seropositive as expected. Elevated EA-D antibody levels and being EBV-seropositive with high titers significantly increased the risk of type-specific oral HPV persistence among these men.