The status of human papillomavirus (HPV)
infection in urothelial
inverted papilloma was examined in the present study.
Formalin-fixed and
paraffin-embedded tissues from eight cases of
inverted papilloma of the bladder were studied. The presence of HPV-
DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of
inverted papilloma. Three cases were diagnosed as
inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one
inverted papilloma with atypia, and HPV-16 was detected in four cases, including one
inverted papilloma with atypia. Multiple HPV type
infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular
proteins, p16-INK4a and mcm7, which are
surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in
inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical
inverted papilloma tissue. High-risk
HPV infection may be one of the causes of urothelial
inverted papilloma, and
inverted papilloma with atypia may have malignant potential.