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

Published:August 06, 2012DOI:https://doi.org/10.1016/j.jaad.2012.05.029

      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 p16INK4a 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.

      Key words

      Abbreviations used:

      adjPeIN (adjacent penile intraepithelial neoplasia), HPV (human papillomavirus), hrHPV (high-risk human papillomavirus), PeIN (penile intraepithelial neoplasia), PSCC (penile squamous cell carcinoma), SCC (squamous cell carcinoma)
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