Effect of HPV-Associated p16INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck

Abstract

Purpose A subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16^INK4A in these tumors. We evaluated p16^INK4A as a prognostic marker of treatment response and survival in a well-defined and prospectively collected cohort of patients treated solely with conventional radiotherapy in the Danish Head and Neck Cancer Group (DAHANCA) 5 trial. Patients and Methods Immunohistochemical expression of p16^INK4A was analyzed in pretreatment paraffin-embedded tumor blocks from 156 patients treated with conventional primary radiotherapy alone. The influence of p16^INK4A status on locoregional tumor control, disease-specific survival, and overall survival after radiotherapy was evaluated. Results p16^INK4A positivity was found in 35 tumors (22%). Tumor-positivity for p16^INK4A was significantly correlated with improved locoregional tumor control (5-year actuarial values 58% v 28%; P = .0005), improved disease-specific survival (72% v 34%; P = .0006), and improved overall survival (62% v 26%; P = .0003). In multivariate analysis, p16^INK4A remained a strong independent prognostic factor for locoregional failure (hazard ratio [HR], 0.35; 95% CI, 0.19 to 0.64), disease-specific death (HR, 0.36; 95% CI, 0.20 to 0.64), and overall death (HR, 0.44; 95% CI, 0.28 to 0.68). Conclusion Expression of p16^INK4A has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy.