Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16^INK4a expression, and prognosis

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• 作者：Carla Ferrá ; ndiz-Pulido ; MD^a ; ^d ; ^{40879cfp@comb.cat} ; Emili Masferrer ; MD^e ; ^f ; Ines de Torres ; MD^b ; Belen Lloveras ; MD^g ; ⁱ ; Javier Hernandez-Losa ; PhD^b ; Sergio Mojal ; BMS^h ; Carlos Salvador ; MD^c ; Juan Morote ; MD^c ; Santiago Ramon y Cajal ; MD^b ; Ramon M. Pujol ; MD^f ; Vicente Garcia-Patos ; MD^a ; ^d ; Agustin Toll ; MD^d ; ^f
• 关键词：human papillomavirus ; p16INK4a ; penile intraepithelial neoplasia ; penis ; squamous cell carcinoma ; survival
• 刊名：Journal of the American Academy of Dermatology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：68
• 期：1
• 页码：73-82
• 全文大小：748 K

文摘

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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.