Incidence and Outcomes of HPV-Associated Head and Neck Cancers in the United States: A Large Population-Based Analysis

Abstract

Human papillomavirus (HPV)-associated oropharyngeal cancers are increasing in the United States (US); yet there are no large epidemiologic studies to define the national burden of HPV-associated head and neck squamous cell carcinomas (HNSCC) of oropharynx and non-oropharynx subsites. A custom Surveillance, Epidemiology, and End Results (SEER) database identified 5,936 patients with HNSCC (oropharynx, nasopharynx, hypopharynx, or other pharynx) and known HPV status, diagnosed from 2013-2014. Age-adjusted HPV-positive HNSCC incidence rates per 100,000 persons were calculated using SEER*Stat. Associations between HPV status and cancer-specific mortality (CSM) were determined using multivariable Fine-Gray competing-risks regression. From 2013-2014, the US incidence of HPV-positive versus negative HNSCC was 2.43 (95% Confidence Interval [CI] 2.35-2.50) versus 1.28 (1.22-1.33) per 100,000 persons, respectively. HPV-positive incidence was 2.26 (2.19-2.34), 0.06 (0.05-0.07), 0.06 (0.05-0.07), and 0.04 (0.01-0.03) for oropharynx, nasopharynx, hypopharynx, and other pharynx HNSCC, respectively. White (2.80, 2.71-2.90), non-Hispanic (2.68, 2.59-2.77) and male patients (4.38, 4.23-4.53) had the highest incidences of HPV-positive disease, with a unimodal age incidence distribution peaking at ages 60-64 (8.04, 7.49-8.62); notably, non-Hispanic white men ages 60-64 had an incidence of 18.56 (17.09-20.13). HPV-positive disease was associated with lower CSM in oropharynx HNSCC (Adjusted Hazard Ratio [AHR] 0.40, P<0.001; 23-month CSM 4.5% versus 11.2%), but not in non-oropharynx HNSCC (AHR 1.08, P=0.81; 23-month CSM 12.2% versus 11.4%), Poropharynx*HPV interaction = 0.002. This large epidemiological study defines the US burden of HPV-associated HNSCC. The highest incidence of US incidence of HPV-positive HNSCC was in non-Hispanic white men, where it represents the sixth most common non-skin solid malignancy in patients 64 and younger. The favorable prognosis associated with HPV appears to be limited to the oropharynx.