Prognostic Significance of HPV DNA and p16INK4a in Anal Cancer: A Systematic Review and Meta-Analysis

We conducted a systematic review and meta-analysis of observational studies evaluating survival in patients with anal cancer, according to human papillomavirus (HPV) DNA, p16(INk4a), and combined HPV DNA/p16(INK4a) status, We systematically searched PubMed, EMBASE, and Cochrane Library databases to identify studies published in English until July 25, 2018, directly providing or allowing estimation of survival of patients with anal cancer according to the presence of HPV DNA and/or overexpression of p16(INK4a). We estimated pooled HRs and 95% confidence intervals (CI) for overall survival (OS) using a random-effects model. We included 16 studies, comprising 1,724 patients with anal cancer tested for HPV DNA (65% positive), and 567 patients tested for p16(INK4a) la (87% positive). The pooled HR for OS was 0.54 (95% CT, 0.33-0.89) for HPV DNA positive versus negative, 0.37 (95% Cl, 0.24-0.57) for p16(INK4a) positive versus negative, and 0.36 (95% CI, 0.22-0.58) for HPV DNA positive/p16(INK4a) positive versus HPV DNA positive/p16(INK4a) negative patients with anal cancer. Patients with HPV DNA or ploIN"a positive anal cancer have significantly better OS compared with HPV DNA or p16(INK4a) negative. This points to the possible value of HPV DNA and/or p16(INK4a) testing when planning the management and follow-up strategy for patients diagnosed with anal cancer.