The association between human papillomavirus type 16 seropositivity and oropharyngeal cancer among men living with HIV

Background: There are no methods for the early detection of human papillomavirus–driven oropharyngeal squamous cell carcinoma (HPV+OPSCC); however, HPV16 E6 seropositivity has been identified as a promising screening marker. Although people living with HIV have a higher risk of developing HPV+OPSCC, few studies have evaluated the association between HPV16 antibodies and HPV+OPSCC. Methods: The association between HPV16 seropositivity (L1, E1, E2, E4, E6, and E7) and OPSCC was assessed among 2331 men living with HIV (MLWH) aged ≥40 years who had blood specimens banked within the Tennessee Center for AIDS Research biorepository between 2001 and 2019; some samples were collected before OPSCC diagnosis, and others after. The association between HPV16 seropositivity and OPSCC was analyzed via univariable logistic regression. Results: One hundred and thirty-five HPV16 E6 seropositive cases and 11 OPSCC cases were identified. HPV16 E6 seropositivity was associated with a 14-fold higher odds of OPSCC (odds ratio [OR], 14.04; 95% CI, 4.23–46.61; p <.001); five of the 11 OPSCC cases were HPV16 E6 seropositive (sensitivity, 45%; 95% CI, 17%–77%) compared to 6% of controls (specificity, 94%; 95% CI, 93%–95%). Seroreactivity against HPV16 E1 (OR, 7.14; 95% CI, 1.52–33.67; p =.013), HPV16 E2 (OR, 16.43; 95% CI, 4.94–54.65; p <.001), and HPV16 E7 (OR, 13.84; 95% CI, 3.99–48.11; p <.001) was also significantly associated with OPSCC. HPV16 E6 antibodies were detectable up to 9 years before and 19 years after OPSCC diagnosis. Conclusions: Among MLWH, HPV16 E6 antibodies are strongly associated with OPSCC, yet point estimates of the sensitivity and specificity of HPV16 E6 antibodies for OPSCC were lower compared to studies in populations without HIV.