Human papillomavirus shows highly variable prevalence in esophageal squamous cell carcinoma and no significant correlation to p16INK4a overexpression: a systematic review.
BACKGROUND
This review investigates the role of p16(INK4a) 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 p16 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 p16(INK4a) was detected in 33.9% (n = 209) of 617 specimens. The HPV presence varied from 0% to 70% among the studies. The prevalence of p16(INK4a) 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 p16(INK4a) 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 p16(INK4a) 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 p16(INK4a) is not a reliable marker of HPV status in ESCC.
Department of Otorhinolaryngology, Head and Neck Surgery and Audiology University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
Sanne Høxbroe
SH
Michaelsen
Christian Grønhøj
CG
Larsen
Christian
C
von Buchwald
D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000821:virology; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology*; D011237:Predictive Value of Tests; D015995:Prevalence
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral