Abstract
BACKGROUND: Human papillomavirus (HPV) has emerged as a major cause of head and neck cancer (HNC), yet nationwide HPV-stratified disease data are still lacking in China. The literature remains divided on the prognostic impact of HPV infection. METHODS: The HNC patients treated from 1 January 2017 to 30 June 2021 were retrospectively identified at nine tertiary A centers representing the seven geographic regions of China. Event-free survival (EFS) and cancer-specific survival (CSS) were estimated with the Kaplan-Meier method and compared using the log-rank test. Early survival differences by subsite and HPV status were assessed using restricted mean survival time differences for EFS (ΔRMEFST) and CSS (ΔRMCSST), adjusting for confounders with pseudo-value regression. RESULTS: The study included 345 cases. Most of the Chinese HNC patients in this study were male (84.64%), and more than one-third were already at clinical Tumor-Node-Metastasis (cTNM) stage IV at diagnosis. Among the 237 patients who underwent HPV testing, 18.99% were HPV-positive, with the highest prevalence in oropharyngeal cancers (37.29%) and the lowest in laryngeal cancers (7.48%; p < 0.001). A higher proportion of HPV‑positive patients consumed alcohol (44.44%), received radiotherapy (53.33%) and chemotherapy (88.89%), whereas a lower proportion underwent surgery (62.22%) (all p < 0.001). In oral cancer, EFS was higher in the HPV-positive group (log-rank p = 0.002); after adjustment for confounders, the 12-month ΔRMEFST was 1.576 months (95%CI = 0.157, 2.996; p = 0.029). Among patients with oropharyngeal cancer, both EFS and CSS were higher in the HPV-positive group than in the HPV-negative group (all log-rank p < 0.050). After multivariable adjustment, the 12-month ΔRMCSST was 0.629 months (95%CI = 0.019, 1.238; p = 0.043). Laryngeal cancer patients showed no HPV-related differences in EFS or CSS (all p > 0.050). A 24-month landmark sensitivity analysis confirmed the survival advantage in oral and oropharyngeal cancer. CONCLUSIONS: Demographics, risk profiles, presentation, and treatment patterns differ sharply by HPV status. Early survival is better for HPV-positive oral and oropharyngeal cancers but not for laryngeal cancer.