6003

Background: The favorable prognosis for HPV-positive (pos) OPC requires confirmation in a clinical trial of sufficient size to account for confounding variables including smoking. Methods: A correlative study was performed to evaluate the association of tumor HPV status (THS) and survival in a randomized phase 3 trial comparing standard fractionation (FX) radiotherapy (RT) and cisplatin (cis) (100 mg/m², days 1, 22, 43) to accelerated FX-RT and cis (100 mg/m², days 1, 22). THS for OPC cases was determined by HPV16 in situ hybridization (ISH). Two-year overall (OS, death) and progression-free survival (PFS, progression, salvage surgery, death) for patients with HPV-pos and HPV-negative [neg] OPC were estimated along with 95% confidence intervals (CIs) by Kaplan-Meier method and compared by log-rank test. Hazard ratios (HR) for OS/PFS comparing HPV-pos to HPV-neg OPC after adjustment for treatment assignment, age, race, T and N stage, and smoking (< or ≥ 20 pack-years [p-y]) were estimated by use of Cox models along with 95% CIs with multiple imputation for cases with undetermined THS and/or missing p-y. Results: THS was evaluable for 73% (317/433) of OPC cases and 60.6% (55.2–65.9) were HPV16-positive. OS/PFS outcomes were similar for cases with and without HPV determination. After median follow-up of 4.4 years, cases with HPV-pos OPC had better OS (p < 0.0001; 2-year 87.5% [82.8–92.2] vs 67.2% [58.9–75.4]) and PFS (p < 0.0001; 2-year 71.9% [65.5–78.2] vs 51.2% [42.4–59.9]). Patients with HPV-pos OPC had a 59% reduction in risk of death (HR 0.41 [0.27–0.64]) and a 46% reduction in risk of progression or death (HR 0.54 [0.37–0.78]). Results with and without imputation were consistent. The hazard of death was elevated for HPV-neg OPC with ≥ 20 p-y (HR 4.33), HPV-neg OPC with < 20 p-y (HR 2.41), and HPV-pos OPC with ≥ 20 p-y (HR 1.79), relative to HPV-pos OPC with <20 p-y. Second primary tumors were less common among HPV-pos cases and patterns of first failure were similar. Conclusions: Tumor HPV status is strongly associated with OS/PFS among OPC patients receiving standard of care chemo-radiation, and should now be a stratification factor for all clinical trials including OPC cases, and separate trials based on THS should be considered.

No significant financial relationships to disclose.