Females Have Worse Overall and Disease-Specific Survival in Human Papillomavirus–Negative Oropharyngeal Squamous Cell Carcinoma

Abstract

Although sex (male vs female) has been identified as an independent prognostic factor in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), the role of sex in HPV-negative OPSCC is less understood. The purpose of this study is to measure the association between sex and HPV-negative OPSCC disease-specific survival (DSS) and overall survival (OS). This longitudinal, retrospective study examined cases of HPV-negative OPSCC diagnosed in the United States between 2013 and 2016 from the Surveillance, Epidemiology, and End Results database. Patients with primary OPSCC and known HPV-negative status were included. Those with HPV-positive or unknown status and primary lesions located outside the oropharynx were excluded. The primary predictor variable was patient sex (male vs female). Primary outcome variables of interest included DSS and OS. The following patient-level covariates were also assessed: age, race, insurance status, primary anatomical site and histological type of lesion, histologic grade and stage, and disease outcome. A survival analysis was conducted using univariate and multivariate analyses via a cox proportional hazard regression model. An α value less than 0.05 was considered statistically significant. The study sample consisted of 2,565 cases (25.1% female) of HPV-negative OPSCC. Females presented with lower histologic grade (P=.015) and earlier stage (P=.003). Females demonstrated worse DSS (P<.001) and OS (P<.001). After multivariate adjustment, female sex (hazard ratio [HR]= 1.38; 95% confidence interval [CI], 1.13 to 1.67; P=.002), advanced age (HR= 1.672; 95% CI, 1.07 to 2.60; P=.023), advanced overall stage (HR= 4.69; 95% CI, 1.54 to 14.267; P=.006), TNM stage (T4: HR= 5.74; 95% CI, 3.86 to 8.55, P<.001, N3: HR= 3.48; 95% CI, 2.17 to 5.58; P<.001, and M1: HR= 2.80; 95% CI, 2.09 to 3.74; P<.001), subjects residing in counties with the highest rates of smoking (HR= 1.29; 95% CI, 1.01 to 1.65; P=.044), and the lack of surgical treatment in patients treated with radiation and/or chemotherapy (HR= 1.44; 95% CI, 1.08 to 1.91; P=.012) were correlated with poorer DSS and OS. Females with HPV-negative OPSCC demonstrated worse DSS and OS despite better typical prognostic signs such as histologic grade and clinical stage.