Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: correlation with pathologic subtypes, p16(INK4a) expression, and prognosis.

Abstract

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, p16(INK4a) 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. P16(INK4a) 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 p16(INK4a) immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical overexpression. Both hrHPV-positive and p16(INK4a)-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. P16(INK4a) immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16(INK4a) staining should be incorporated in histologic evaluation of PSCC.

• Authors: 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
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 68 Issue 1 Pg. 73-82 (Jan 2013) ISSN: 1097-6787 [Electronic] United States
• PMID: 22863066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma in Situ (metabolism, pathology, virology)
• Carcinoma, Squamous Cell (metabolism, pathology, virology)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Genotype
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Papillomaviridae (genetics, isolation & purification)
• Papillomavirus Infections (epidemiology)
• Penile Neoplasms (metabolism, pathology, virology)
• Prevalence
• Prognosis
• Retrospective Studies
• Spain (epidemiology)