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Tytuł:
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Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.
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Autorzy:
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Martins VDCA; Department of Education and Research, Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil.; Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.; Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil.
Cunha IW; Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.; Department of Pathology, Rede D'OR- São Luiz, São Paulo, Brazil.
Figliuolo G; Department of Education and Research, Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil.; Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
Rondon HHMF; Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.
de Souza PM; Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
Torres Silva FL; Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.
Torres Silva GL; Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
de Souza Bastos M; Department of Virology, Fundação de Medicina Tropical Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
de Castro DB; Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil.; Technical Advisory, Fundação de Vigilância em Saúde do Amazonas, Manaus, Amazonas, Brazil.
Santana MF; Department of Education and Research, Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil.; Department of Virology, Fundação de Medicina Tropical Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
Ramasawmy R; Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil.; Department of Virology, Fundação de Medicina Tropical Heitor Vieira Dourado, Manaus, Amazonas, Brazil.; Faculdade de Medicina, Universidade Nilton Lins, Manaus, Amazonas, Brazil.
Levi JE; Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.
Torres KL; Department of Education and Research, Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil.; Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.; Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil.
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Źródło:
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PloS one [PLoS One] 2020 May 06; Vol. 15 (5), pp. e0232474. Date of Electronic Publication: 2020 May 06 (Print Publication: 2020).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: San Francisco, CA : Public Library of Science
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MeSH Terms:
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Papillomaviridae*/genetics
Papillomaviridae*/pathogenicity
Cyclin-Dependent Kinase Inhibitor p16/*genetics
Epstein-Barr Virus Infections/*complications
Papillomavirus Infections/*complications
Penile Neoplasms/*etiology
Penile Neoplasms/*virology
Adult ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; DNA, Viral/genetics ; DNA, Viral/isolation & purification ; Epstein-Barr Virus Infections/virology ; Genetic Markers ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/isolation & purification ; Human papillomavirus 16/genetics ; Human papillomavirus 16/pathogenicity ; Human papillomavirus 18/genetics ; Human papillomavirus 18/pathogenicity ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; Penile Neoplasms/epidemiology ; Risk Factors ; Up-Regulation ; Young Adult
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References:
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Substance Nomenclature:
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0 (CDKN2A protein, human)
0 (Cyclin-Dependent Kinase Inhibitor p16)
0 (DNA, Viral)
0 (Genetic Markers)
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Entry Date(s):
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Date Created: 20200507 Date Completed: 20200731 Latest Revision: 20231113
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Update Code:
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20240105
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PubMed Central ID:
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PMC7202603
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DOI:
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10.1371/journal.pone.0232474
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PMID:
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32374757
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Background: In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a is a surrogate sensitive marker of HPV infection in PC.
Objectives: To correlate p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region.
Methods: Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra.
Results: The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%.
Conclusions: p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.
Competing Interests: The authors have read the journal’s policy and have the following conflicts: author Isabela Werneck Cunha IW is affiliated with The Rede D’OR- São Luiz. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
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