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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000166
Original Articles

Human Papillomavirus Shows Highly Variable Prevalence in Esophageal Squamous Cell Carcinoma and No Significant Correlation to p16INK4a Overexpression: A Systematic Review

Michaelsen, Sanne Høxbroe BSc Med; Larsen, Christian Grønhøj MD; von Buchwald, Christian MD, DMSc

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Abstract

Introduction:

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.

Methods:

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.

Results:

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.

Conclusions:

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.

Copyright © 2014 by the International Association for the Study of Lung Cancer

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