Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão.
A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67.
Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank).
Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.
BMC cancer. 2022 Oct 15*** epublish ***
Antonio Augusto Lima Teixeira Júnior, Syomara Pereira da Costa Melo, Jaqueline Diniz Pinho, Thaís Bastos Moraes Sobrinho, Thalita Moura Silva Rocha, Denner Rodrigo Diniz Duarte, Liseana de Oliveira Barbosa, Wesliany Everton Duarte, Marta Regina de Castro Belfort, Kelly Gomes Duarte, Antonio Lima da Silva Neto, José de Ribamar Rodrigues Calixto, Lúcio Cristiano Paiva Paiva, Francisco Sérgio Moura Silva do Nascimento, Antonio Machado Alencar Junior, André Salim Khayat, Rita da Graça Carvalhal Frazão Corrêa, Joyce Santos Lages, Rodolfo Borges Dos Reis, Wilson Silva Araújo, Gyl Eanes Barros Silva
Department of Genetics and Postgraduate Program in Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Higher Education Center of Zé Doca, State University of Maranhão, Zé Doca, Brazil., Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil., Postgraduate Program in Clinical Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., University Hospital of the Federal University of Maranhão, São Luís, Brazil., Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil., Oncology Research Center, Federal University of Pará, Belém, Brazil., Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil. .