The Influence of HPV-Status on Outcome of Anal Cancer Treated with Radio-Chemotherapy

To evaluate the HPV infection- and transformation-status as a potential predictor of the response to definitive radio-chemotherapy for anal cancer. One hundred six patients (63 women, 43 men) with histologically confirmed anal cancer and known HPV-Infection- and p16-expression-status were evaluated. All patients were treated with definitive radio-chemotherapy (RCT) with 5-FU/MMC. Median Age was 59 yrs (range, 35 – 86 yrs), median follow-up of living patients was 47 mo (2-205). Sixty patients were simultaneously HPV+ and p16+ (group 1), 9 patients were HPV+/p16- (group 2), 11 patients were HPV-/p16+ (group 3) and 23 patients were HPV-/p16- (group 4). Endpoints were local control (LC) at 5 years and overall survival (OS) at 5 years. In addition to HPV/p16 status, the influence of age, gender, previous surgery, T-stage, N-Status and tumor localization (canal vs margin) were analyzed. Seventy-two (68%) pts. were HPV positive. More women than men were HPV+ (women 70% vs men 30%). In univariate analysis, small T-Stage (T1/2), female gender, previous complete resection, and HPV/p16 status showed significant influence on LC. HPV+/p16+ patients showed significantly better LC (87.5%) in contrast to HPV-/p16+ (63.6%; p = 0.016) and especially HPV-/p16- pts. (55.8%; p = 0.001), but not when compared to HPV+/p16- pts. (77.8%; p = 0.302). OS was influenced by T-Stage, previous surgery, and LC. HPV+/p16+ pts. showed a trend toward better OS compared to HPV-/p16- (81.8% versus 68.8%; p = 0.075). Upon multivariate analysis, T3/4-stage and HPV/p16 status (HPV-/p16+, HPV-/p16-) predicted poorer LC (T1/2: 86.6% vs T3/4: 50.3% LC, HR = 4.21; 95% CI = 1.72-10.28; p = .002; group 1 vs group 3 HR = 4.51; 95% CI = 1.27-16.04; p = 0.020, and group 1 vs group 4 HR = 5.64; 95% CI = 1.91-16.62; p = 0.002), while local relapse predicted shorter OS (0% vs 91.9%, HR = 18.88; 95% CI = 6.53-54.58; p < 0.001). Our data suggest that patients with HPV+/p16+ disease had the best prognosis, while patients with HPV-/p16+ and HPV-/p16- disease showed the worst outcome and therefore require therapy optimization, particularly given that LC is the most important factor for overall survival. Pooling of data or large scale prospective studies will be needed to further dissect the relative importance of HPV- vs p16-status.