Objective: To determine if the human papilloma virus (HPV) is associated with improved overall survival (OS) in all head and neck sub-sites.
Method: Data were extracted from the National Cancer Database of patients diagnosed with head and neck squamous cell carcinomas from 2010-2014. Patients were classified based on the location of their primary malignancy into the six main sub-sites of head and neck (oral cavity, oropharynx, nasopharynx, hypopharynx, larynx and nasal cavity & sinuses).
Results: We identified a total of 41,950 patients (16,644 with high risk HPV, 25,306 with HPV negative tumors. Each sub-site: oral cavity, oropharynx, nasopharynx, hypopharynx, larynx and nasal cavity & sinuses consisted of 9,080, 21,627, 1,006, 1,931, 7,725 and 581 patients respectively. HPV-positive patients were more likely to be younger, white and male, present with earlier T staging tumors and have poor differentiation on histology.
On Kaplan-Meier 5 year OS analysis, major survival differences were noted in the oropharynx and hypopharynx (OP: 77.6% vs. 50.7% p<0.001; HP: 52.2% vs. 28.8% p<0.001) between HPV-positive and HPV negative patients respectively. Moderate survival differences were found in oral cavity, larynx and nasal cavity & sinuses (OC: 59.4% vs. 53.1% p=0.002; LRX: 57.2% vs. 48.7% p<0.001, NC&S: 63.1% vs. 45.1% p=0.003). No statistically significant survival difference was noted in the nasopharynx (NP: 52.5% vs. 58.7% p=0.728).
On multivariate analysis, HPV status remained an independent prognostic factor for four sub-sites oral cavity, oropharynx, hypopharynx and larynx (OC: HR 0.76, 95% CI 0.68-0.83, p<0.001, OP: HR 0.44, 95% CI 0.40-0.48, p<0.001, HP: HR 0.59, 95% CI 0.46-0.73, p<0.001, LRX: HR 0.71, 95% CI 0.62-0.80, p<0.001) after accounting for age, sex, race, Charleson/Deyo comorbidity score, insurance, income, T and N staging and primary treatment. For the sub-sites nasopharynx and nasal cavity & sinuses, HPV status was not associated with overall survival (NP: HR 1.03, 95% CI 0.87-1.20, p=0.813; NC&S: HR 0.63, 95% CI 0.39-0.87, p=0.056).
Conclusion: HPV plays a varying role in prognosis of head and neck cancers at different sub-sites. In oropharynx and hypopharynx, HPV is strongly prognostic of improved survival. In oral cavity and larynx, HPV is moderately associated with improved survival. In nasopharynx and nasal cavity/sinuses, HPV plays no role in prognosticating overall survival.