Detection of Human Papillomavirus Infection and p16 Immunohistochemistry Expression in Bladder Cancer with Squamous Differentiation

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.