Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

TLDR

HPV‑positive oropharyngeal cancer patients have lower progression risk than HPV‑negative patients, but it is unclear whether HPV status also reduces mortality after progression. This study retrospectively examined whether tumor p16 status predicts overall survival after disease progression in stage III–IV oropharyngeal squamous cell carcinoma patients treated with platinum‑based chemoradiotherapy. Kaplan‑Meier estimates and Cox proportional hazards models, stratified by treatment protocol, were applied to 181 patients (105 p16‑positive, 76 p16‑negative). p16‑positive tumors were associated with markedly better post‑progression survival (2‑year OS 54.6% vs 27.6%, median 2.6 vs 0.8 years; HR 0.48) and, together with salvage surgery, reduced death risk, whereas distant progression increased risk, indicating HPV status is an independent prognostic factor and should guide trial stratification.

Abstract

Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced.Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol.A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment.Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.