Year of Publication



Public Health

Date Available


Degree Name

Master of Public Health (M.P.H.)

Committee Chair

Krystle Kuhs

Committee Member

Jay Christian

Committee Member

Rachel Hogg-Graham

Committee Member

Jaclyn McDowell



Objective: The incidence of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is surging in the United States, particularly in the southeast and Appalachia. The reason for this increase is unknown. We evaluated the prevalence of two markers of increased risk, HPV16 E6 antibodies and oral HPV infection, among men in Appalachian and non-Appalachian Kentucky.

Methods: This study was nested within an ongoing HPV-OPC screening study of healthy men aged 45+ residing in urban (non-Appalachian) and rural (Appalachian) Kentucky and included the first 1,581 participants with either HPV serologic and/or oral HPV testing. Blood and oral rinse samples were collected at enrollment. Blood samples (N=1,363) were assessed for HPV16 antibodies using multiplex serology. Oral samples (N=1,507) were tested for HPV16, HPV18 and/or other high-risk HPVs using the AmpFire genotyping assay. Prevalence of HPV16 antibodies (L1, E1, E2, E4, E6, E7) and oral HPV were assessed overall and by Appalachian status. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for determinants of HPV16 E6 seropositivity and oral HPV.

Results: Overall, 4.99% had at least 1 HPV16 antibody detected, 1.32% (N=18) were HPV16 E6 seropositive; 7.43% were high-risk oral HPV positive, 3.19% were HPV16+, and 0.46% were HPV18+. Appalachian men were significantly more likely to be positive for at least 1 HPV16 antibody (6.61% vs. 3.38%, OR 2.02 [95% CI: 1.21 to 3.38], P=0.007); yet, seroprevalence of individual HPV16 antibodies was non-significantly elevated due to sample size: L1 (1.62% vs. 0.73%), E1 (1.44% vs. 0.29%), E2 (0.73% vs. 0.59%), E4 (2.35% vs. 1.17%), E6 (1.32% vs. 1.32%), and E7 (1.03% vs. 0.73%). High-risk oral HPV was non-significantly elevated among Appalachian men (8.23% vs. 6.40%; OR: 1.30 [95%CI: 0.89-1.90]); HPV16 (3.53% vs. 2.74%), and HPV18 (0.59% vs. 0.30%). Current smoking status (OR 2.42, 95% CI: 1.57 to 3.76, P<0.001) and >20 pack-years of smoking (OR: 1.78, 95%CI: 1.09 to 2.90, P<0.021) were significantly associated with high-risk oral HPV. HPV16 E6 seropositivity was strongly associated with oral HPV16 (OR: 13.5, 95%CI: 4.5 to 40.78, P<0.001).

Conclusion: The prevalence of several risk factors for HPV-OPC are elevated in Kentucky, particularly among Appalachian men.

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