Locally advanced hypopharyngeal and laryngeal cancer: Influence of HPV status

Larynx preservation with chemoradiotherapy (CRT) is used frequently in the treatment of locally advanced hypopharyngeal/laryngeal squamous cell carcinoma (LSCC). Multiple large retrospective analyses have shown that CRT is associated with worse overall survival (OS) compared to total laryngectomy (TL) in patients with T4a disease. Burgeoning evidence suggests HPV status may play a prognostic role in patients with LSCC. We aimed to determine if HPV status influences OS among patients with T4a LSCC, and, if so, if it may be useful in selecting patients for CRT.

Using the National Cancer Database (NCDB), we identified 810 patients with T4a N0-3 M0 squamous cell carcinoma of the larynx or hypopharynx with known HPV status who received either definitive CRT (to 66-81.6 Gy with any chemotherapy) or definitive TL (with the addition of 60-70 Gy of adjuvant RT). We evaluated differences in OS using the Kaplan-Meier method and Cox proportional hazards analyses.

On multivariate analysis, HPV-negative status (HR = 1.42, p = 0.02) and receipt of CRT (HR = 1.34, p = 0.01) were associated with worse OS when compared to HPV-positive patients and patients receiving TL, respectively. Among patients receiving CRT, 5-year OS was lower among HPV-negative patients (33.4%) when compared to HPV-positive patients (50.6%).

These data suggest that HPV status may be a prognostic factor in patients with T4a LSCC. Further, it supports further investigation into the usefulness of HPV status as a selection factor for larynx preservation with CRT in these patients.