BACKGROUND: One third to one half of penile squamous cell carcinomas (SCCs) are related to human papillomavirus (HPV) infection. Viral detection is usually carried out by polymerase chain reaction (PCR) or other molecular methods. In this study, we evaluated p16(INK)⁴(a) immunohistochemical expression, which is simpler and less costly, as a potential marker of high-risk HPV (HR-HPV) infection in penile SCC. DESIGN AND METHODS: We pathologically classified 202 invasive penile carcinomas and performed HPV genotyping by short PCR fragment (SPF)₁₀ PCR and p16(INK)⁴(a) immunohistochemistry. We also evaluated HPV and p16(INK)⁴(a) according to the histologic subtypes of penile SCC. Tumors depicting continuous p16(INK)⁴(a) immunostain in all neoplastic cells were considered positive. HPV and p16(INK)⁴(a) status were compared using classifier performances and concordance indexes. RESULTS: Evidence of HPV (low-risk and high-risk genotypes) was found in 63 cases (31%) by PCR. Fifty-three p16(INK)⁴(a)-positive cases were identified (26%). Overexpression of p16(INK)⁴(a) had a sensitivity of 67% and a specificity of 91% for defining the HPV status. Concordance indexes between p16(INK)⁴(a) and HPV status were high (≥78%) in general cases and in all histologic subtypes of penile SCC. The stain was useful in the differential diagnosis of basaloid and low-grade warty carcinomas. Low-risk HPV genotypes were found in 5 tumors, 4 of which were p16(INK)⁴(a) negative. Basaloid and nonbasaloid high-grade (grade 3) SCCs were more likely to be HR-HPV positive when compared with grades 1 to 2 tumors (P<0.000001 and 0.0417, respectively). CONCLUSIONS: p16(INK)⁴(a) overexpression was found to be a reliable marker for HR-HPV and a helpful tool in the differential diagnosis of low-grade verruciform and high-grade solid penile tumors. SCC variants depicting basaloid features were more likely to be HPV and p16(INK)⁴(a) positive than low-grade, keratinizing lesions. We also observed a tendency toward HPV positivity in high-grade nonbasaloid tumors. Our results indicated a concordance between HPV and p16(INK)⁴(a) status and this observation may have diagnostic and prognostic implications.
BACKGROUND: One third to one half of penile squamous cell carcinomas (SCCs) are related to human papillomavirus (HPV) infection. Viral detection is usually carried out by polymerase chain reaction (PCR) or other molecular methods. In this study, we evaluated p16(INK)⁴(a) immunohistochemical expression, which is simpler and less costly, as a potential marker of high-risk HPV (HR-HPV) infection in penile SCC. DESIGN AND METHODS: We pathologically classified 202 invasive penile carcinomas and performed HPV genotyping by short PCR fragment (SPF)₁₀ PCR and p16(INK)⁴(a) immunohistochemistry. We also evaluated HPV and p16(INK)⁴(a) according to the histologic subtypes of penile SCC. Tumors depicting continuous p16(INK)⁴(a) immunostain in all neoplastic cells were considered positive. HPV and p16(INK)⁴(a) status were compared using classifier performances and concordance indexes. RESULTS: Evidence of HPV (low-risk and high-risk genotypes) was found in 63 cases (31%) by PCR. Fifty-three p16(INK)⁴(a)-positive cases were identified (26%). Overexpression of p16(INK)⁴(a) had a sensitivity of 67% and a specificity of 91% for defining the HPV status. Concordance indexes between p16(INK)⁴(a) and HPV status were high (≥78%) in general cases and in all histologic subtypes of penile SCC. The stain was useful in the differential diagnosis of basaloid and low-grade warty carcinomas. Low-risk HPV genotypes were found in 5 tumors, 4 of which were p16(INK)⁴(a) negative. Basaloid and nonbasaloid high-grade (grade 3) SCCs were more likely to be HR-HPV positive when compared with grades 1 to 2 tumors (P<0.000001 and 0.0417, respectively). CONCLUSIONS:p16(INK)⁴(a) overexpression was found to be a reliable marker for HR-HPV and a helpful tool in the differential diagnosis of low-grade verruciform and high-grade solid penile tumors. SCC variants depicting basaloid features were more likely to be HPV and p16(INK)⁴(a) positive than low-grade, keratinizing lesions. We also observed a tendency toward HPV positivity in high-grade nonbasaloid tumors. Our results indicated a concordance between HPV and p16(INK)⁴(a) status and this observation may have diagnostic and prognostic implications.
Authors: José Vassallo; André Fellipe Freitas Rodrigues; Antonio Hugo J F M Campos; Rafael Malagoli Rocha; Isabela Werneck da Cunha; Stênio Cássio Zequi; Gustavo Cardoso Guimarães; Francisco Paulo da Fonseca; Ademar Lopes; Antonio Cubilla; Fernando Augusto Soares Journal: Tumour Biol Date: 2015-01-05
Authors: Karl Kashofer; Elke Winter; Iris Halbwedl; Andrea Thueringer; Marisa Kreiner; Stefan Sauer; Sigrid Regauer Journal: Mod Pathol Date: 2017-04-07 Impact factor: 7.842
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