Abstract
The role of p16INK4a as a surrogate marker for screening human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) remains controversial. 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). 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). 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.
Highlights
Esophageal carcinoma ranks ninth in cancer incidence and sixth in cancer mortality around the world [1]
The pooled results showed no significant relationship between p16INK4a expression and human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) based on overall HPV types (OR: 1.79, 95% confidence intervals (CIs): 0.69-4.66, p = 0.235)
Previous studies have demonstrated that p16INK4a is highly expressed in oropharyngeal squamous cell carcinoma patients who have been infected by HPV [12,13,14]
Summary
Esophageal carcinoma ranks ninth in cancer incidence and sixth in cancer mortality around the world [1]. Previous studies have demonstrated that p16INK4a is highly expressed in oropharyngeal squamous cell carcinoma patients who have been infected by HPV [12,13,14]. P16INK4a was strongly expressed in patients with head and neck squamous cell carcinoma [7, 15] and patients with cervical squamous cell carcinoma [16, 17] who had been infected by HPV. Some [18,19,20,21,22] suggested that p16INK4a may play an important role in the development of ESCC in patients infected with HPV, but others [23,24,25,26,27] hold an opposite view. In an attempt to clarify the controversy, we undertook this meta-analysis to evaluate the relationship between p16INK4a expression and HPV in ESCC
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