HPV Status and Survival Outcomes in Patients 70 Years and Older After Surgery for Oropharyngeal Carcinoma

Importance: The incidence of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) arising from the palatine tonsil and base of the tongue (BOT) is increasing among the older population. However, data on the prognostic impact of HPV status in patients 70 years and older who undergo up-front surgical treatment remain limited. Objective: To evaluate whether HPV status is associated with survival outcomes in patients 70 years or older undergoing surgical treatment for squamous cell carcinoma (SCC) of the tonsil or BOT. Design, setting, and participants: This was a retrospective cohort analysis including patients 70 years or older at the time of diagnosis with biopsy specimen-proven and surgically resectable SCC of the tonsil or BOT treated in 10 comprehensive cancer centers from January 1, 2010, to July 31, 2021, with a minimum follow-up period of 3 years. Data analysis was conducted from August 20 to December 23, 2024. Exposure: HPV status determined by p16 immunohistochemistry. Main outcomes and measures: Overall survival (OS) and disease-free survival (DFS) were compared between p16-positive and p16-negative groups using Cox proportional hazards models. Results: The analysis included 345 patients (mean [SD] age, 75.7 [4.8] years; 241 [69.9%] male), of whom 207 (60.0%) underwent a transoral surgical approach and 138 (40.0%), an open surgical technique. Of these, 155 patients (44.9%) had p16-positive and 190 (55.1%) had p16-negative test results. The median (IQR) follow-up duration was 55 (18-87) months. Patients with p16-positive tumors demonstrated significantly improved survival outcomes. Specifically, the 5-year OS rate was 71.4% for patients who had p16-positive vs 47.7% for p16-negative test results, with an absolute difference of 23.7% (95% CI, 13.0%-34.4%) and an adjusted hazard ratio (HR) for OS of 0.36 (95% CI, 0.23-0.57). Similarly, the 5-year DFS rate was 66.4% for patients who were p16-positive compared to 40.8% for those p16-negative, with an absolute difference of 25.6% (95% CI, 14.9%-36.3%) and an adjusted HR for DFS of 0.42 (95% CI, 0.28-0.63). Conclusions and relevance: This cohort study found that p16 positivity was associated with significantly improved survival outcomes, suggesting that HPV-associated tumors maintain their favorable prognosis even in patients 70 years and older who were surgically treated for SCC of the tonsil or BOT.