Improved Survival of Patients With Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial

TLDR

Retrospective studies suggest HPV‑positive head and neck squamous cell carcinoma has a better prognosis than HPV‑negative disease, but prospective confirmation is lacking. This study prospectively assessed how tumor HPV status relates to treatment response and survival in 96 stage III/IV oropharyngeal or laryngeal HNSCC patients enrolled in an ECOG phase II trial. Patients received two cycles of paclitaxel/carboplatin induction chemotherapy followed by weekly paclitaxel with standard radiation; HPV status was determined by multiplex PCR and in situ hybridization, and survival outcomes were analyzed with Kaplan–Meier and multivariable Cox models. Forty percent of tumors were HPV‑positive, and these patients had higher response rates after induction (82% vs 55%) and chemoradiation (84% vs 57%), a 2‑year overall survival of 95% versus 62%, and significantly lower risks of progression (HR 0.27) and death (HR 0.36) compared with HPV‑negative patients, confirming a strong association between HPV status and favorable outcomes.

Abstract

The improved prognosis for patients with human papillomavirus (HPV)–positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan–Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.