Valquíria do Carmo Alves Martins1,2,3, Isabela Werneck Cunha4,5, Giuseppe Figliuolo1,6, Heidy Halanna de Melo Farah Rondon2, Paloma Menezes de Souza6, Felipe Luz Torres Silva2, Guilherme Luz Torres Silva6, Michele de Souza Bastos7, Daniel Barros de Castro3,8, Monique Freire Santana1,7, Rajendranath Ramasawmy3,7,9, José Eduardo Levi10, Kátia Luz Torres1,2,3. 1. Department of Education and Research, Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil. 2. Universidade Federal do Amazonas, Manaus, Amazonas, Brazil. 3. Genomic Health Surveillance Network: Optimization of Assistance and Research in The State of Amazonas - REGESAM, Manaus, Amazonas, Brazil. 4. Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil. 5. Department of Pathology, Rede D'OR- São Luiz, São Paulo, Brazil. 6. Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil. 7. Department of Virology, Fundação de Medicina Tropical Heitor Vieira Dourado, Manaus, Amazonas, Brazil. 8. Technical Advisory, Fundação de Vigilância em Saúde do Amazonas, Manaus, Amazonas, Brazil. 9. Faculdade de Medicina, Universidade Nilton Lins, Manaus, Amazonas, Brazil. 10. Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.
Abstract
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.
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.
Authors: Juan Chipollini; Grant Pollock; Chiu-Hsieh Hsu; Ken Batai; Alejandro Recio-Boiles; Benjamin R Lee Journal: Cancer Med Date: 2021-10-10 Impact factor: 4.452
Authors: 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 Journal: BMC Cancer Date: 2022-10-15 Impact factor: 4.638