Prognostic Factors for Survival in Human Papilloma Virus Positive Head and Neck Squamous Cell Carcinoma

Abstract

Objectives: The TNM classification of human papillomavirus (HPV) associated tumors does not account for HPV/p16 status or that the cervical metastases tend to be cystic, which artifactually increases the size of the affected nodes. Our study objective was to review the outcomes of patients with HPV associated squamous cell carcinoma (SCC) of the oropharynx and unknown primary treated at our institution from 2008-2011. Methods: A retrospective review of patients at our institution from 2008-2011 identified 199 patients with p16 positive squamous cell carcinoma of unknown primary or of the oropharynx. Results: Of the 199 patients, 177 (89%) were males, 182 (92%) were Caucasian, 135 (68%) were ≤ 60 years old, 85 (43%) were non-smokers, 187 (94%) arose from the oropharynx, 139 (70%) had T stage ≤2, 47 (24%) had N ≤1, and 20 (10.1%) were p16 positive but HPV DNA negative by in situ hybridization (ISH). On multivariate analysis of disease-free survival (DFS), increased age (hazard ratio [HR] = 1.05 P = 0.02), ECOG status ≥1 (HR = 3.09 P = 0.002), T3/4 vs. T0/1/2 (HR 2.27 P = 0.02), N2C vs. N1/N0 (HR = 2.77 P = 0.02) and receiving induction chemotherapy versus definitive chemoradiotherapy (HR = 5.13 P = 0.02) were associated with worse DFS. p16 and HPV DNA positivity (HR 0.41 P = 0.03) was associated with improved DFS. Conclusions: Our data suggest that nodal size may not be as important as number of nodes in HPV positive disease. Furthermore, dual positivity of p16 and HPV DNA compared to p16 alone has a positive impact on prognosis suggesting a biologic difference between them.