Prevalence of high-risk human papillomavirus in primary squamous cell carcinoma of urinary bladder

Studies have demonstrated an etiologic role of high-risk human papillomavirus (HR-HPV) infection for epithelial malignancies, including most cervical carcinomas, anogenital cancers, and carcinomas of the head and neck; however, a causative role of HPV infection for bladder cancer is controversial. The purpose of this study was to investigate the prevalence of HR-HPV in primary bladder carcinoma to determine the association between HPV infection and the squamous cell component of urothelial carcinoma of the bladder. Furthermore, we evaluated the utility of p16 overexpression as a surrogate marker for HPV infection in these cancers and the correlation of this with tumor stage. Our study included 33 cases of squamous cell carcinoma (SCC) of the urinary bladder. Tumors deemed primary from the bladder were selected and either showed predominant (>50 %) or pure squamous differentiation. Immunohistochemical study for p16 and HR-HPV by RNA in situ hybridization (ISH) was performed in all cases. p16 expression was detected in 7 cases (28 %, 7/25) of urothelial carcinoma with squamous differentiation and not detected in any of the 8 cases (0%, 0/8) of pure SCC. Detection of HR-HPV by ISH was negative in all 33 cases (0%, 0/33). There was no association between p16 overexpression and the presence of HPV infection in squamous cell carcinomas of the bladder. p16 should not be used as a surrogate marker for evidence of HPV infection. Our study suggests that HPV infection does not play an etiologic role in the development of bladder cancer and should not be used as a diagnostic adjunct for these cases.