Oropharyngeal cancer (OPC) is rare and, in some countries, more than 70% of all cases are caused by human papillomavirus (HPV).1 The type HPV16 accounts for more than 85% of all cases of HPV–associated oropharyngeal cancer (HPV-OPC).1 Antibodies to the HPV16 E6 oncoprotein are biomarkers for determining the HPV status of OPC cases, with reported sensitivities of around 90% and specificities higher than 95%.2 Antibodies can be detected more than 10 years prior to OPC diagnosis.1,3 However, their positive predictive value for HPV-OPC is low, at approximately 1% per year.3,4 Most patients with HPV-OPC also have antibodies to other viral regulatory and oncoproteins (E1, E2, E7)1-3 and have higher antibody levels than seropositive individuals who do not develop cancer.1,3 Currently, there is no consensus on HPV-OPC screening,4 but including these other variables may improve the specificity of HPV-OPC prediction. We examined HPV16 E6, E7, E1, and E2 seropositivity and antibody levels in a cohort of older men who have sex with men (MSM).