Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis

Abstract

To clarify the role of human papillomavirus (HPV) in penile cancer we evaluated the prevalence of HPV DNA in different histological subtypes of penile carcinoma, dysplasia, and condyloma using a novel, sensitive SPF10 HPV polymerase chain reaction assay and a novel genotyping line probe assay, allowing simultaneous identification of 25 different HPV types. Formalin-fixed, paraffin-embedded tissue samples were collected from the United States and Paraguay. HPV DNA was detected in 42% cases of penile carcinoma, 90% cases of dysplasia, and 100% cases of condyloma. There were significant differences in HPV prevalence in different histological cancer subtypes. Although keratinizing squamous cell carcinoma and verrucous carcinoma were positive for HPV DNA in only 34.9 and 33.3% of cases, respectively, HPV DNA was detected in 80% of basaloid and 100% of warty tumor subtypes. There was no significant difference in HPV prevalence between cases from Paraguay and the United States. In conclusion, the overall prevalence of HPV DNA in penile carcinoma (42%) is lower than that in cervical carcinoma (approximately 100%) and similar to vulvar carcinoma (approximately 50%). In addition, specific histological subtypes of penile cancer--basaloid and warty--are consistently associated with HPV, however, only a subset of keratinizing and verrucous penile carcinomas is positive for HPV DNA, and thus these two tumor groups seem to develop along different pathogenetic pathways.

Figures

Figure 1.

Main histological subtypes of penile carcinoma analyzed in the study. A: Keratinizing SCC: infiltrating tumor characterized by nests and tongues of malignant squamous epithelium with prominent central keratin pearls. B: Verrucous carcinoma: exophytic tumor characterized by papillary architecture and pushing invasive border; malignant squamous epithelium is well differentiated and no koilocytic atypia is present. C: Basaloid carcinoma: infiltrating tumor characterized by nests and cords of immature malignant squamous epithelium with areas of central necrosis; foci of keratin pearls may be also present. D: Warty carcinoma: exophytic/infiltrating tumor characterized by papillary architecture and marked cytological atypia with prominent koilocytic features.

Figure 2.

Identification of HPV genotypes using LiPA. LiPA strips with hybridization bands indicating a single HPV type infection: lane 1 = HPV 16; lane 2 = HPV 18; and a multiple HPV type infection: lane 3 = HPV 45 and 70. Note: HPV 18 is reactive with two probes, 18 and c68, and HPV 45 with probes 45 and 45/68.