Prognostic Role of p16 in Non-oropharyngeal Head and Neck Cancer

Abstract

Previous studies have reported conflicting information regarding the prognostic role of p16 in non-oropharyngeal head and neck squamous cell carcinoma (HNSCC). We investigated the association between p16 status and cause-specific mortality in a large sample of United States veterans with oropharyngeal or non-oropharyngeal head and neck cancer (Table 1). Using the United States Veterans Affairs database, we analyzed 8727 patients with locoregionally advanced HNSCC diagnosed between 2005 and 2015 and treated with radiation therapy or chemoradiation therapy. Of these, 1538 had known p16 status, determined by review of clinical notes and pathology reports. We compared outcomes for 1164 patients with oropharyngeal HNSCC and 374 patients with non-oropharyngeal (oral cavity, hypopharyngeal, or laryngeal) HNSCC, using multivariable Cox proportional hazards regression models to test effects on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) within strata. We also tested for significant interactions between p16 and non-oropharyngeal primary site for each outcome. In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16 positive tumors had improved OS, CSS, and CM compared to patients with p16 negative tumors in both oropharyngeal (OS: hazard ratio [HR] 0.57, P<.001; CSS: HR 0.54, P<.001; CM: HR 0.63, P = .04) and non-oropharyngeal primary sites (OS: HR 0.48, P<.001; CSS: HR 0.46, P = .007; CM: HR 0.49, P = .03). The prognostic impact of p16 status did not significantly differ by primary tumor site for OS, CSS, or CM (interaction P values all >.05). Our findings support the hypothesis that p16 has a similar prognostic role in both non-oropharyngeal and oropharyngeal cancer. Strong consideration should be given to routine testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.Abstract 100; Table 1OutcomeModelOropharyngealNon-oropharyngealHazard ratio for p16+ (95% CI)P valueHazard ratio for p16+ (95% CI)P valueOverall survivalUnadjusted0.34 (0.26-0.43)<.0010.52 (0.34-0.79)<.001Adjusted0.61 (0.46-0.80)<.0010.47 (0.31-0.73)<.001Cancer-specific survivalUnadjusted0.28 (0.21-0.39)<.0010.52 (0.30-0.90).02Adjusted0.55 (0.38-0.78)<.0010.42 (0.23-0.74).003Competing MortalityUnadjusted0.43 (0.29-0.65)<.0010.52 (0.28-0.99).05Adjusted0.72 (0.46-1.13).150.53 (0.28-1.02).06 Open table in a new tab