Detection of human papillomavirus infection and p16 immunohistochemistry expression in bladder cancer with squamous differentiation

PLoS One. 2014 Mar 27;9(3):e93525. doi: 10.1371/journal.pone.0093525. eCollection 2014.

Abstract

Objectives: To determine the potential association between HPV infection and the squamous cell component of urothelial carcinoma (UC) of the bladder and to validate p16 overexpression as a surrogate marker for HPV infection in these cancers among Koreans.

Methods: We analyzed the presence of HPV infection using an HPV-DNA chip and the expression of p16 using immunohistochemistry in 47 subjects between July 2001 and March 2011. The study group (n = 35) included patients with squamous differentiation of UC of the bladder. The control group (n = 12) included patients with squamous metaplasia of the bladder.

Results: Baseline characteristics of control and study groups were similar. HPV DNA detection rates were approximately 2-fold higher in the study than the control group (17.1% [6/35] versus 8.3% [1/12], respectively), but the difference was not statistically significant. P16 overexpression was detected in 16/35 (45.7%) study group and 1/12 (8.3%) control group samples (p = 0.034). Both HPV-positivity and p16 overexpression were present in 3/35 (8.8%) study group samples, but none of the control group (p = 0.295). In the study group, the percentage of HPV-positive cases who were non-smokers was 2-fold higher than the percentage of HPV-negative cases who were non-smokers (66.7% [4/6] versus 31.0% [9/29], respectively); however, statistical significance was not achieved due to the small sample size.

Conclusions: HPV infection may be associated with UC of the bladder with squamous differentiation, especially in non-smokers. However, p16 expression does not appear to be a strong surrogate marker for evidence of HPV infection in this type of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Carcinoma, Squamous Cell / virology
  • Cell Differentiation
  • DNA, Viral / genetics*
  • Female
  • Gene Expression
  • Human papillomavirus 16 / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / surgery
  • Papillomavirus Infections / virology
  • Urinary Bladder / pathology
  • Urinary Bladder / surgery
  • Urinary Bladder / virology
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Urinary Bladder Neoplasms / virology

Substances

  • DNA, Viral

Grants and funding

This work was supported by a grant from the National Cancer Center (NCC-1110510), Republic of Korea. However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.