A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease.

Autor: Teixeira Júnior AAL; Department of Genetics and Postgraduate Program in Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil., da Costa Melo SP; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Pinho JD; Higher Education Center of Zé Doca, State University of Maranhão, Zé Doca, Brazil., Sobrinho TBM; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Rocha TMS; Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil.; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Duarte DRD; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., de Oliveira Barbosa L; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., Duarte WE; Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil.; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., de Castro Belfort MR; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil.; Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil., Duarte KG; Postgraduate Program in Clinical Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., da Silva Neto AL; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., de Ribamar Rodrigues Calixto J; University Hospital of the Federal University of Maranhão, São Luís, Brazil., Paiva Paiva LC; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil., do Nascimento FSMS; University Hospital of the Federal University of Maranhão, São Luís, Brazil., Alencar Junior AM; Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil.; University Hospital of the Federal University of Maranhão, São Luís, Brazil., Khayat AS; Oncology Research Center, Federal University of Pará, Belém, Brazil., da Graça Carvalhal Frazão Corrêa R; University Hospital of the Federal University of Maranhão, São Luís, Brazil., Lages JS; University Hospital of the Federal University of Maranhão, São Luís, Brazil., Dos Reis RB; Postgraduate Program in Clinical Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Araújo WS Jr; Department of Genetics and Postgraduate Program in Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Silva GEB; Postgraduate Program in Adult Health, Federal University of Maranhão, São Luís, Brazil. gyl.silva@ufma.br.; Laboratory of Immunofluorescence and Electron Microscopy, University Hospital of the Federal University of Maranhão, São Luís, Brazil. gyl.silva@ufma.br.; Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil. gyl.silva@ufma.br.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2022 Oct 15; Vol. 22 (1), pp. 1063. Date of Electronic Publication: 2022 Oct 15.
DOI: 10.1186/s12885-022-10127-z
Abstrakt: Background: 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.
Methods: 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-p16 INK4a , p53, and ki-67.
Results: 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 p16 INK4a 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).
Conclusions: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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