Abstract LB-181: Oral HPV DNA detection and subsequent risk of head and neck cancers in two prospective cohorts
Authors: Agalliu Ilir , Chen Zigui , Wang Tao , Ludvigsen Rebecca , Teras Lauren , Kreimer Aimee R. , Hayes Richard B. , Gapstur Susan , Burk Robert D. 
Published: August 2015

Abstract
Background: Alpha HPV16 detection in the oral cavity is associated with head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer. However, there have been no prospective studies examining the temporal relationship between oral HPV detection and subsequent risk of HNSCC. Moreover, recent data indicates that the oral cavity contains a plethora of HPV types in addition to alpha HPVs (e.g. beta and/or gamma HPVs), but their association with risk of HNSCC is unknown.
Methods: We examined prospective associations between alpha, beta and gamma HPVs and risk of HNSCC, using a nested case-control design among &gt;120,000 participants with available mouthwash samples in the American Cancer Society (ACS) Cancer Prevention Study-II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A total of N = 132 incident cases of HNSCC (oropharyngeal, oral and laryngeal SCCs) were identified during an average 3.94 years of follow-up (range 0.02-9.0) in both cohorts. Three controls per case (N = 396) were selected using incidence density sampling, with matching on age (±2 years), race/ethnicity, gender, and time since mouthwash collection (±3 months). Detection of HPV DNA in mouthwash samples was carried out using (1) a novel next-generation sequencing assay designed to detect all HPV types, (2) the MY09/MY11 assay targeting alpha-HPV types, and (3) a RT-PCR specific for HPV16. Associations of alpha, beta and gamma HPVs with risk of HNSCC were evaluated using conditional logistic regression models for matched risk sets to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for smoking and alcohol as well as alpha HPV16 for beta and gamma HPVs.
Results: The prevalence of oral HPV16 was 1.8% in controls. HPV16 detection was associated with a 7.1-fold higher risk of overall HNSCC (95% CI 2.2-22.6); the risk was highest for oropharyngeal cancer (OR = 22.41, 95% CI 1.8 - 276.7), while no excess was found for oral cavity or larynx cancers. There were no associations between other alpha HPVs and risk of HNSCC. Oral prevalence of any beta or gamma HPVs was 59.4% and 38.2%, respectively in controls. Detection of any beta HPV (OR = 1.74, p = 0.05) or any gamma HPV (OR = 2.11, p = 0.005) was also associated with risk of HNSCC, with several beta (β1 HPV5, β2 HPV17, β2 HPV38) and gamma (γ11, γ12) HPVs having statistically significant increased risks (ORs from 3.92 to 7.36). In regard to tumor location, β1HPV5 was associated with oropharyngeal (OR = 7.42, p = 0.05), oral cavity (OR = 5.34, p = 0.01) and laryngeal cancers (OR = 2.71, p = 0.05); while β2 HPV38 was associated with oropharyngeal cancer (OR = 7.28, p = 0.02) only. Gamma HPV species groups 11 and 12 were associated with both oral cancer (OR = 7.47, p = 0.03; and OR = 6.71, p = 0.01, respectively) and laryngeal cancers (OR = 7.49, p = 0.04 and OR = 5.31, p = 0.03).
Conclusion: This study is the first to demonstrate that alpha HPV16 detection precedes the incidence of oropharyngeal cancers. Risks identified with other HPV types from gamma11 and 12 species as well as beta HPV5, previously associated with skin cancer, suggests a broader role for HPVs in HNSCC etiology. Readily-collected oral wash samples provide a strong prospective marker for oropharyngeal cancer and, with the incorporation of other HPV types, may indicate risk for a broader spectrum of HNSCC.
Citation Format: Ilir Agalliu, Zigui Chen, Tao Wang, Rebecca Ludvigsen, Lauren Teras, Aimee R. Kreimer, Richard B. Hayes, Susan Gapstur, Robert D. Burk. Oral HPV DNA detection and subsequent risk of head and neck cancers in two prospective cohorts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-181. doi:10.1158/1538-7445.AM2015-LB-181