Effect of HPV-Associated p16^INK4A Expression on Response to Radiotherapy and Survival in Squamous Cell Carcinoma of the Head and Neck

TLDR

HPV infection defines a subset of head and neck cancers, and its presence is closely linked to overexpression of the tumor suppressor p16(INK4A). The study aimed to determine whether p16(INK4A) expression predicts treatment response and survival in patients receiving conventional radiotherapy alone. In a prospective cohort of 156 Danish patients, pretreatment tumor blocks were immunohistochemically stained for p16(INK4A) to assess its status and correlate with locoregional control, disease‑specific, and overall survival. p16(INK4A)-positive tumors (22%) showed significantly better 5‑year locoregional control (58% vs 28%), disease‑specific survival (72% vs 34%), and overall survival (62% vs 26%), and remained an independent prognostic factor in multivariate analysis (HR 0.35–0.44), underscoring its major impact on radiotherapy outcomes.

Abstract

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.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.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).Expression of p16(INK4A) has a major impact on treatment response and survival in patients with head and neck cancer treated with conventional radiotherapy.