This review investigates the role of p16INK4a as a marker of transcriptionally active human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) and the regional prevalence of HPV in ESCC.
PubMed, EMBASE, and the Cochrane Library were systematically searched with the purpose of identifying all studies published between January 1980 and July 2013 reporting both HPV and p16INK4a results in a minimum of five human ESCC specimens.
Twelve studies were identified, providing data on a total of 1383 ESCC specimens collected between 1987 and 2009 from 10 different countries. HPV DNA was detected in 12.0% (n = 161) of 1347 specimens, and p16INK4a was detected in 33.9% (n = 209) of 617 specimens. The HPV presence varied from 0% to 70% among the studies. The prevalence of p16INK4a overexpression in HPV-positive and HPV-negative specimens demonstrated no statistically significant difference, neither for the combined data (p = 0.7507) nor for any individual study, and detection of p16INK4a overexpression did not affect the odds of tumors being HPV positive (odds ratio = 1.0666 with 95% confidence interval 0.7040–1.6157). In a pooled analysis, the sensitivity of p16INK4a overexpression as a marker of HPV DNA presence was 0.35, the specificity 0.67, and the positive predictive value 0.25.
This systematic review reports great regional variation in the prevalence of HPV in ESCC and suggests that p16INK4a is not a reliable marker of HPV status in ESCC.