TY - JOUR
T1 - Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16INK4a expression, and prognosis
AU - Ferrándiz-Pulido, Carla
AU - Masferrer, Emili
AU - De Torres, Ines
AU - Lloveras, Belen
AU - Hernandez-Losa, Javier
AU - Mojal, Sergio
AU - Salvador, Carlos
AU - Morote, Juan
AU - Ramon Y Cajal, Santiago
AU - Pujol, Ramon M.
AU - Garcia-Patos, Vicente
AU - Toll, Agustin
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - human papillomavirus
KW - p16 INK4a
KW - penile intraepithelial neoplasia
KW - penis
KW - squamous cell carcinoma
KW - survival
U2 - 10.1016/j.jaad.2012.05.029
DO - 10.1016/j.jaad.2012.05.029
M3 - Article
SN - 0190-9622
VL - 68
SP - 73
EP - 82
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 1
ER -