Robust Differences in Distant Metastases for p16 ± OPSCC: Implications for Future Targeted Therapy

Abstract

Objectives:

Historically, head and neck squamous cell carcinoma (HNSCC) has been considered a lymphatic malignancy with regional disease. Recently, this has been called into question. Our study aims to (1) illustrate the robust differences between p16+ and p16- oropharyngeal squamous cell carcinoma (OPSCC), and (2) provide circumstantial evidence that p16+ OPSCC has a predilection toward active vasculature invasion and hematogenous spread.

Methods:

A multi-institutional, retrospective study of 1060 patients with OPSCC undergoing definitive treatment between 1979 and 2012. Patients were divided into 2 cohorts: p16+ and p16- OPSCC. Differences in distant metastases (DM) between the 2 cohorts were assessed for risk factors, rate and temporal differences, phenotypic behavior, and post-DM progression-free and disease-specific survival.

Results:

Of the 1060 patients, 105 patients had DM. Thirty-four were p16- and 71 were p16+. Full statistical analysis has yet to be completed, but preliminary findings conclude that of the p16- patients with DM, only 6% had disseminated disease (distant metastases at >1 site) as compared with 70% of p16+ patients with DM. Distant disease in p16+ patients included brain and unique bilateral lung findings.

Conclusions:

Our large, multi-institutional study supports the previously reported claim that patients with p16+ OPSCC have a unique phenotypic disseminated behavior. This calls into question the belief that HNSCC is a lymphatic malignancy. Our data suggest that p16+ disease has a predilection toward active vasculature invasion evidenced by atypical end-organ DM and dissemination profile. This study’s findings coupled with data in the literature may have implications for future p16+ OPSCC targeted therapy.