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.
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: Kamran Zargar-Shoshtari; Philippe E Spiess; Anders E Berglund; Pranav Sharma; Julio M Powsang; Anna Giuliano; Anthony M Magliocco; Jasreman Dhillon Journal: Clin Genitourin Cancer Date: 2015-12-23 Impact factor: 2.872
Authors: Julie Steinestel; Andreas Al Ghazal; Annette Arndt; Thomas J Schnoeller; Andres J Schrader; Peter Moeller; Konrad Steinestel Journal: BMC Cancer Date: 2015-04-03 Impact factor: 4.430
Authors: Vicenilma de Andrade Martins; Jaqueline Diniz Pinho; Antonio Augusto Lima Teixeira Júnior; Leudivan Ribeiro Nogueira; Fábio França Silva; Victor Eduardo Maulen; André Salim Khayat; José de Ribamar Rodrigues Calixto; Herikson Araújo Costa; Leandra Naira Zambelli Ramalho; Gyl Eanes Barros Silva Journal: PLoS One Date: 2018-10-12 Impact factor: 3.240
Authors: Marilia Freitas Calmon; Mânlio Tasso de Oliveira Mota; Érica Babeto; Natália Maria Candido; Ana Paula Girol; Carlos Fabian Mendiburu; Jane Lopes Bonilha; Rodrigo Vellasco Duarte Silvestre; Bruno Miziara Rosa; Jorge Alberto Thomé; Gustavo Hernandez Américo Medeiros; Fernando Augusto Soares; Gustavo Cardoso Guimarães; José Germano Ferraz de Arruda; Sonia Maria Oliani; Luisa Lina Villa; José Vassallo; Paula Rahal Journal: PLoS One Date: 2013-01-14 Impact factor: 3.240