Squamous cell carcinoma of the oropharynx (SCCOP) caused by human papillomavirus (HPV) accounts for more than half of all cases of head and neck cancers. While survival of HPV-associated SCCOP is better than SCCOP caused by tobacco, a considerable number of patients still do poorly. Most patients are treated with intensive, multi-modality therapy approaches incurring long-term toxicities. Identification of biomarkers and development of risk stratification models will allow individualized treatment strategies to minimize overtreatment and associated adverse effects. Tumor HPV status and presence of antibodies to HPV oncoproteins predict both risk and prognosis of SCCOP. Genome-wide associatio...

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Squamous cell carcinoma of the oropharynx (SCCOP) caused by human papillomavirus (HPV) accounts for more than half of all cases of head and neck cancers. While survival of HPV-associated SCCOP is better than SCCOP caused by tobacco, a considerable number of patients still do poorly. Most patients are treated with intensive, multi-modality therapy approaches incurring long-term toxicities. Identification of biomarkers and development of risk stratification models will allow individualized treatment strategies to minimize overtreatment and associated adverse effects. Tumor HPV status and presence of antibodies to HPV oncoproteins predict both risk and prognosis of SCCOP. Genome-wide association studies (GWAS) consistently report that genetic factors, including immunogenic variation, play a role in HPV-associated SCCOP and may, in part, explain the marked heterogeneity in survival among patients. Understanding how genetic immunovariants (variants in immune-related genes) interact with tumor HPV status will help develop improved prognostic biomarkers for SCCOP. We propose the following aims to test our hypotheses that HPV serostatus and immunovariants interact to determine survival of SCCOP patients: 1) To determine if the blood-based non-tumor biomarkers HPV16 E serostatus and GWAS-based genetic immunovariants predict survival among 2,286 SCCOP patients; 2) To investigate the interaction between HPV serostatus and immunovariants in determining survival among SCCOP patients; and 3) To validate significant associations found in the discovery cohort using an independent external cohort of 1,519 SCCOP patients from INHANCE consortium. Our study will identify specific HPV serology patterns and immunovariants that predict survival of SCCOP patients that could have a significant role in the clinical management of SCCOP patients with the potential to increase survival while minimizing treatment-related side-effects of the treatments to improve patient quality of life.

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