Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer

摘要

Purpose: Oropharyngeal squamous cell carcinoma (OPSCC) associated with human papilloma virus (HPV) is rapidly growing in incidence. Despite better prognosis than OPSCC associated with traditional risk factors, treatment failure still occurs in a significant proportion of patients. We had identified the antiapoptotic protein Bd2 as a marker for poor outcome in advanced OPSCC treated with concurrent chemoradiation. To determine whether Bd2 and HPV together might further characterize treatment response, we examined whether the prognostic value of Bd2 was independent of HPV status.Experimental Design: Pretreatment tumor biopsies from 68 OPSCC patients were tested for HPV by in situ hybridization and were immunostained for Bd2 to evaluate relations with disease-free (DFS) and overall survival following platin-based concurrent chemoradiation. Median follow-up among surviving patients was 47 months (range, 10-131 months).Results: Bd2 and HPV independently predicted DFS and overall survival. Hazard ratios (with 95% confidence interval) for positive versus negative status in bivariate Cox proportional hazard analysis of DFS were 6.1 (1.8-21) for Bd2 and 0.11 (0.035-0.37) for HPV. Only 1 of 32 HPV-positive/Bd2-negative tumors recurred. Pretreatment Bd2 expression was spedfically assodated with distant metastasis; five of six distant metastases occurred in the <40% of patients whose primary tumors were Bd2 positive.Conclusions: Independent of HPV status, pretreatment Bd2 expression identifies a subset of OPSCC patients having increased risk of treatment failure, particularly through distant metastasis, after concurrent chemoradiation. Considering HPV and Bd2 together should help in devising better personalized treatments for OPSCC. Clin Cancer Res