HPV status to predict outcome for anal cancer treated with radiochemotherapy.
4065 Background: Evaluation of the HPV infection- and transformation-status as a predictor of the response to definitive radio-chemotherapy for anal cancer. Methods: 80 patients (54 fm, 26 m) with histologically confirmed anal cancer and known HPV-Infection- (determined by PCR) and p16-expression-status (determined by immunohistochemistry) were analyzed. All pts. were treated with definitive radio-chemotherapy (RCT) with 5-FU/MMC, median age 60ys (35–86), median follow up 54mo (4–180). 41 pts. were HPV+ and p16+ (group 1), 10 pts. were HPV-/p16+ (group 2), 9 pts. were HPV+/p16- (group 3) and 17 pts. were HPV+/p16- (group 4). Endpoints were local control (LC) at 5ys and overall survival (OS) at 5ys. In addition to HPV/p16 status, the influence of T-stage and tumor localization (canal vs. margin) was analyzed. Results: More women than men were HPV+ (fm 77% vs. m 33%) while gender was evenly distributed among HPV-pts. (fm 48% vs. m 53%). Upon univariate analysis, gender, HPV+ and p16+ were significant predictors of both LC and OS (p<0.05) while T-Stage was predictive for LC (p<0.05). Upon multivariate analysis, gender and T-Stage significantly influenced LC (w85.2% vs. m54.9%, p=0.028; <T3 84.2% vs ≥ T3 48,1%, p=0,019). OS was significantly influenced by gender (w95% vs. m59.2%, p=0.005), while the influence of HPV/p16-status did not reach significance when all four groups were analyzed simultaneously in this moderately sized cohort. Upon direct univariate comparison of HPV+/p16+ und HPV-/p16-pts, both gender and combined HPV/p16-positivity had a significant influence on LC and OS. Upon multivariate analysis, combined HPV/p16-positivity resulted in better LC (HPV+/p16+: 85% vs. HPV-/p16-: 38.7%, p=0.003), while, as a consequence of moderate patient numbers, only gender significantly predicted OS (fm93.7% vs. m62.6%, p=0.015). Viral status, however, showed a trend for significance. Conclusions: The data from one of the largest monocentric series treated with a uniform treatment regimen suggest that HPV-status predicts response to RCT in pts. with anal cancer. Patients with tumors not associated with HPV whatsoever (HPV-/P16-) have both inferior LC and a clear trend for inferior OS and might require an intensified treatment regimen.