Human Papillomavirus Is Associated With Improved Overall Survival in Patients With Non-Oropharyngeal Squamous Cell Carcinomas Presenting With Metastatic Disease

Abstract

Human papillomavirus (HPV) is a favorable prognostic marker for patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-metastatic non-OPSCC of the head and neck. We evaluated the impact of HPV status on overall survival (OS) for patients with Stage IVC non-OPSCC. Patients diagnosed between 2010 and 2013 with Stage IVC non-OPSCC and known HPV status were identified in the National Cancer Database. Univariate and multivariate analyses were performed with Cox proportional hazards to determine factors associated with OS. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in OS analyses. The multiple imputation method was used for sensitivity analysis. We identified 708 patients with Stage IVC non-OPSCC with 30% being HPV positive. Unadjusted median survival was 10.3 months for HPV-negative patients and 21.4 months for HPV-positive patients (P < .0001). Age ≥ 65 (HR: 1.47; 95% CI 1.08-2.01) and tumor diameter (HR: 1.13; 95% CI 1.03-1.25) were associated with worse OS while treatment (HR 0.29; 95% CI 0.19-0.43) and HPV-positive status (HR 0.43; 95% CI 0.29-0.64) were associated with improved OS on multivariate analysis. Adjusted median survival for patients with HPV-negative and HPV-positive disease was 11.1 months and 23.8 months, respectively (P < .01). On subgroup analysis, patients with HPV-positive oral cavity disease exhibited improved outcomes (P < .0001) while HPV-positive hypopharynx and larynx patients exhibited a trend for improved OS compared to HPV-negative patients. The survival advantage associated with HPV positivity was maintained on sensitivity analysis (HR 0.66; 95% CI 0.48-0.92). These data demonstrate a clinically meaningful association between HPV status and overall survival in patients with non-oropharyngeal squamous cell carcinomas presenting with Stage IVC disease. In the absence of randomized data, these findings support active consideration of HPV status in clinical decision making, clinical trial design, and patient counseling regarding prognosis.