Prognostic Significance of P16(INK4a) Expression in Penile Squamous Cell Carcinoma: A Meta-Analysis with Trial Sequential Analysis

BACKGROUND: Recently, P16(INK4a) expression has been shown to be correlated with cancer-specific survival (CSS) in penile squamous cell carcinoma (SCC). Therefore, we performed this meta-analysis to clarify the prognostic value of P16(INK4a) for penile SCC. METHODS: A systematic search was performed in PubMed, Embase, and Web of Science to identify all relevant articles up to May 25, 2017. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of included studies were pooled to estimate the prognostic value. Trial sequential analysis (TSA) was performed to assess the quantity and strength of survival evidence. RESULTS: Five retrospective studies consisting of 323 cases were finally included. We found that P16(INK4a) positive expression was significantly associated with a better CSS of penile SCC (HR=0.45, 95%CI: 0.30-0.67, P<0.001). No heterogeneity or publication bias was noted among the included studies. Furthermore, TSA demonstrated that the findings were based on sufficient evidence. CONCLUSIONS: P16(INK4a) positive expression is independently associated with improved CSS for patients with penile SCC.