Evolution of hazard of recurrence and death after surgery for oropharyngeal cancer according to HPV status

Background: Human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative disease. However, limited evidence is available on how the risk of recurrence and cancer-related death evolves according to HPV status. Methods: This multicentre retrospective cohort study included patients who underwent upfront surgery with neck dissection for OPSCC between 2010 and 2022. HPV status was determined by p16 immunohistochemistry. Overall survival, cancer-specific survival, disease-free survival, and disease-free specific survival were estimated using Kaplan–Meier methods. Time-varying hazard rates (HR) for cancer-related death, local recurrence, regional recurrence, distant metastasis, and secondary primary tumor were estimated over a five-year period using nonparametric smoothed hazard functions, stratified by p16 status. Results: Among 650 patients, 284 (43.7%) had p16-positive tumours. Cancer-related mortality peaked during the second postoperative year in both groups, but occurring earlier and at markedly higher levels in p16-negative than in p16-positive patients (15 vs 18 months; annual HR: 12.7% vs 4.1%). Local and regional recurrence risks were the highest within the first two years, remained significantly higher and more prolonged in p16-negative patients than in p16-positive counterpart. The risk of second primary tumors was higher for p16-negative patients than p16-positive ones, remaining almost constant during follow-up in both groups. Conclusions: The risk of recurrence and cancer-related death after surgery for OPSCC differs in magnitude and in timing according to p16 status. Hazard function analysis provides clinically relevant information beyond conventional survival estimates and may support time-adapted follow-up strategies and patient counselling in OPSCC.