p16INK4a is not a reliable screening marker of hpv infection in esophageal squamous cell carcinoma: Evidence from a meta-analysis

Abstract

Background: The role of p16INK4a as a surrogate marker for screening human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) remains controversial. Methods: A comprehensive search of EMBASE, PubMed, China National Knowledge Infrastructure and China Biology Medicine was performed from inception to December 27, 2015. A random-effects model was applied to the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Ten studies were identified (985 cases). The pooled results showed no significant relationship between p16INK4a expression and HPV infection in ESCC based on overall HPV types (OR:1.79, 95% CI:0.69-4.66, p = 0.235). Subgroup analysis by HPV detection method showed no statistical significance in either the polymerase chain reaction (PCR) (OR:1.65, 95% CI:0.83-3.30, p = 0.154) or in situ hybridization (ISH) group (OR:2.58, 95% CI:0.03-268.14, p = 0.689). The pooled OR of the sensitivity analysis ranged from 1.27 (95% CI:0.58-2.84) to 2.32 (95% CI:0.95-5.64). Of these studies, 6 involved only high-risk human papillomavirus types (HR-HPV), HPV16 or HPV18. However, similar observations were made for HR-HPV (OR = 1.31, 95% CI:0.26-6.59, p = 0.741). Subgroup analysis again showed no statistical significance in the PCR group (OR:0.95, 95% CI:0.25-3.64, p = 0.940) and ISH group (OR:2.58, 95% CI:0.03-268.14, p = 0.689). Sensitivity analysis showed that the pooled OR ranged from 0.69 (95% CI:0.21-2.22) to 1.89 (95% CI:0.33-10.86). Conclusions:p16INK4a is not a reliable screening marker of HPV infection in ESCC. Further multicenter, large-sample and well-matched prospective studies are still required to illuminate the possible etiological roles of HPV in ESCC.