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

Carla Ferrándiz-Pulido, Emili Masferrer, Ines De Torres, Belen Lloveras, Javier Hernandez-Losa, Sergio Mojal, Carlos Salvador, Juan Morote, Santiago Ramon Y Cajal, Ramon M. Pujol, Vicente Garcia-Patos, Agustin Toll

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47 Citations (Scopus)


Background: Penile 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. Objective: We 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. Methods: A 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. Results: HPV 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 p16 INK4a immunohistochemical overexpression. Both hrHPV-positive and p16INK4a-positive tumors showed a better overall survival without reaching statistical significance. Limitations: This was a retrospective study. Conclusions: Our 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. © 2012 by the American Academy of Dermatology, Inc.
Original languageEnglish
Pages (from-to)73-82
JournalJournal of the American Academy of Dermatology
Issue number1
Publication statusPublished - 1 Jan 2013


  • human papillomavirus
  • p16 INK4a
  • penile intraepithelial neoplasia
  • penis
  • squamous cell carcinoma
  • survival


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