Oncogenic Human Papillomaviruses are Rarely Associated with Squamous Cell Carcinoma of the Bladder: Evaluation by Differential Polymerase Chain Reaction

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Abstract
While a strong association between oncogenic human papillomaviruses and squamous cell cancers of the genital tract (penis, urethra and cervix) is known to exist, there is substantial controversy regarding the association of human papillomaviruses and cancers of the bladder. Technical issues regarding assay technique and concern about potential contamination have marred interpretation of previous work. Moreover, because human papillomavirus has been associated predominantly with squamous cell cancers at other sites, any involvement of human papillomavirus and bladder epithelial carcinogenesis must address whether any association between human papillomavirus and squamous cell carcinoma of the bladder exists. Differential polymerase chain reaction and a rigorous protocol to avoid crossover contamination were used to analyze archival bladder carcinoma specimens (22 squamous cell carcinomas and 20 transitional cell carcinomas). Type specific primers for human papillomavirus types 16 and 18 were used as were general primers to detect types 6b, 11, 13, 16, 18, 31, 32, 33, 35, 45 and 51. Only 1 of 22 squamous cell carcinoma specimens (4.4%) was positive (human papillomavirus type 18)--a cadaveric renal transplant patient on chronic immunosuppression. Cervical specimens were human papillomavirus negative in this patient. No human papillomavirus deoxyribonucleic acid was detected in the 20 transitional cell carcinoma cohort. Our results confirm that these human papillomavirus types appear to have little association with invasive transitional cell cancers. Of greater significance, despite this (to our knowledge) first reported case of human papillomavirus type 18 detected in squamous cell carcinoma of the bladder (seen in an immunocompromised patient), we conclude that these oncogenic human papillomavirus types do not have a significant role in squamous cell carcinogenesis of the bladder.