Robust Differences in p16-Dependent Oropharyngeal Squamous Cell Carcinoma Distant Metastasis: Implications for Targeted Therapy

Objective. Historically, head and neck squamous cell carcinoma (HNSCC) has been earmarked a lymphatic malignancy. Recently, this has been called into question. Our study aims to (1) illustrate the robust differences in distant metastases between p16+ and p16 oropharyngeal squamous cell carcinoma (OPSCC) and (2) provide support that p16+ OPSCC has a predilection toward vasculature invasion and hematogenous spread. Study Design. Multi-institutional, case series with chart review. Setting. Four academic institutions. Subjects and Methods. Within a group of 1113 patients with primary OPSCC who received treatment between 1979 and 2013, those who developed distant metastasis (DM) were divided into 2 cohorts based on p16 status. Intergroup and intragroup univariate analysis was performed as well as descriptive analysis of end-organ sites. Results. Of the 1058 patients included, 89 developed DM. Thirty were p16 and 59 were p16+. Of the p16 patients with DM, only 10% had disseminated disease (distant metastases at ≥2 sites) compared with 74% of p16+ patients. Distant disease in p16+ patients included brain, abdomen, and a distinct pattern of pulmonary metastases. Conclusion. Our large, multi-institutional study supports published reports that p16+ OPSCC metastasizes with a unique phenotype that is hematogenous and widely disseminated with atypical end-organ sites. Our data suggest that p16+ OPSCC has a predilection toward active vasculature invasion as evidenced by the results and illustrative radiologic and pathohistologic examples. These findings may have implications for future targeted therapy when treating p16+ OPSCC.