Anatomical Distribution of Human Papillomavirus Infection in the Lower Urinary Tract of Men with Bladder Cancer Undergoing Radical Cystectomy

We investigated the anatomical distribution of human papillomavirus (HPV) infection in the lower urinary tract of men with bladder cancer undergoing radical cystectomy. In total, 79 anterior urethral samples, 99 prostatic urethral specimens, 74 bladder tumor specimens, and 87 non-tumor bladder specimens were collected from 102 patients. After DNA extraction from each formalin-fixed paraffin-embedded tissue specimen, HPV-DNA was examined by nested polymerase chain reaction, and HPV genotypes were determined by Sanger sequencing. In situ hybridization (ISH) was used to localize HPV-DNA in positive samples, and E6/E7 mRNA ISH was performed to assess transcriptional activity. HPV-DNA was detected at any site in 16 (15.7%) of 102 patients, with site-specific detection rates of 8.0% (7/87) in non-tumor bladder mucosa, 5.1% (4/79) in the anterior urethra, 4.1% (3/74) in bladder tumor tissue, and 4.0% (4/99) in the prostatic urethra. HPV16 was detected in 11 samples, and HPV18 in 7 samples. HPV-DNA ISH signals were observed in 12 (66.7%) of 18 HPV-positive specimens, and E6/E7 mRNA signals were present in 2 of 18 specimens. HPV-DNA was detected at various sites of the lower urinary tract. E6/E7 mRNA expression in a bladder cancer specimen warrants further research on the biological relevance of HR-HPV infection.