Importance: The incidence of HPV-associated OPSCC has increased at an epidemic rate over the last 30 years. Patients with HPV-associated OPSCC experience better treatment response and survival outcomes compared to HPV-negative OPSCC. The treatment of OPSCC has evolved to include single or combined modalities and is largely dependent upon HPV/p16 positivity and smoking history. The survival benefit of chemotherapy in the post-surgical treatment of OPSCC is unclear, especially in the setting of HPV-OPSCC.
Objective: To determine the survival benefit of postoperative chemoradiotherapy (CRT) versus postoperative radiotherapy (RT) in the management of patients with advanced-stage OPSCC (7th Edition AJCC) when stratifying patients based on p16 and smoking status. We hypothesized the survival benefit of postoperative CRT is dependent on both the p16 and smoking status of the patient.
Design, setting, and participants: A retrospective cohort of OPSCC patients undergoing curative intent treatment between January 1, 1998 – December 31, 2009 were identified through a provincial cancer registry. All patients included in the study were diagnosed and treated at a high-volume tertiary care centre for head and neck oncology. p16 positivity was determined from formalin-fixed paraffin embedded tissues using a tissue microarray design and cut-off values accepted by the College of American Pathologists.
Exposures: Postoperative chemotherapy for OPSCC.
Main outcomes and measures: Comparative univariate and multivariate survival analyses were performed between patients who received surgery (S) + CRT and S + RT, stratified according to p16 status and tobacco smoking history (≥10 pack years).
Results: Patients with OPSCC treated with S + CRT compared to patients treated with S + RT alone showed a significantly higher 5-year overall survival regardless of p16 or smoking status (n=138, 77% versus 58.1%, p = 0.014). Patients with a smoking history, regardless of the p16 status, also showed an overall survival benefit with the addition of postoperative chemotherapy to RT compared to postoperative RT alone (n = 99, 73.8% versus 48.1%, p = 0.017). When further stratified by both p16 and smoking status, p16-positive patients with a smoking history had significantly higher overall survival when treated with postoperative CRT versus postoperative RT alone (n = 58, 83.8% versus 57.7%, p = 0.029). p16-OPSCC non-smokers did not have a significant survival benefit when treated with chemotherapy in the postoperative setting (n=24, 75% versus 100%, p = 0.136).
Conclusions and relevance: In OPSCC treated with surgery and post-operative RT, the addition of chemotherapy may improve survival in select patients, mainly HPV-positive smokers. The risk versus benefit of postoperative CRT vs postoperative RT alone in OPSCC should be further investigated.