Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16INK4a expression, and prognosis

BackgroundPenile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established.ObjectiveWe sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16INK4a immunostaining, and prognosis.MethodsA total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16INK4a immunohistochemical expression on tissue microarrays was also analyzed.ResultsHPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16INK4a immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16INK4a immunohistochemical overexpression. Both hrHPV-positive and p16INK4a-positive tumors showed a better overall survival without reaching statistical significance.LimitationsThis was a retrospective study.ConclusionsOur results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16INK4a immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16INK4a staining should be incorporated in histologic evaluation of PSCC.