title: 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.
authors.affiliation:  Department of Thoracic Surgery, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Wang
authors.affiliation:  School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan Province - China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wu
authors.affiliation:  Department of Pathology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Jing-Li
authors.initials: JL
authors.lastname: Ren
authors.affiliation:  Department of Thoracic Surgery, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation:  Department of Pathology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chang
authors.affiliation:  Department of Pathology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Gui-Ming
authors.initials: GM
authors.lastname: Hu
authors.affiliation:  Department of Pathology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province - China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Wu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D055088:Early Detection of Cancer; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16