Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0232474 |
| _version_ | 1818405173819604992 |
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| author | Valquíria do Carmo Alves Martins Isabela Werneck Cunha Giuseppe Figliuolo Heidy Halanna de Melo Farah Rondon Paloma Menezes de Souza Felipe Luz Torres Silva Guilherme Luz Torres Silva Michele de Souza Bastos Daniel Barros de Castro Monique Freire Santana Rajendranath Ramasawmy José Eduardo Levi Kátia Luz Torres |
| author_facet | Valquíria do Carmo Alves Martins Isabela Werneck Cunha Giuseppe Figliuolo Heidy Halanna de Melo Farah Rondon Paloma Menezes de Souza Felipe Luz Torres Silva Guilherme Luz Torres Silva Michele de Souza Bastos Daniel Barros de Castro Monique Freire Santana Rajendranath Ramasawmy José Eduardo Levi Kátia Luz Torres |
| author_sort | Valquíria do Carmo Alves Martins |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T08:51:51Z |
| format | Article |
| id | doaj.art-49199dc739764dd9a6ff7827e50173ab |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:51:51Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-49199dc739764dd9a6ff7827e50173ab2022-12-21T23:09:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01155e023247410.1371/journal.pone.0232474Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.Valquíria do Carmo Alves MartinsIsabela Werneck CunhaGiuseppe FigliuoloHeidy Halanna de Melo Farah RondonPaloma Menezes de SouzaFelipe Luz Torres SilvaGuilherme Luz Torres SilvaMichele de Souza BastosDaniel Barros de CastroMonique Freire SantanaRajendranath RamasawmyJosé Eduardo LeviKátia Luz TorresBACKGROUND: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.https://doi.org/10.1371/journal.pone.0232474 |
| spellingShingle | Valquíria do Carmo Alves Martins Isabela Werneck Cunha Giuseppe Figliuolo Heidy Halanna de Melo Farah Rondon Paloma Menezes de Souza Felipe Luz Torres Silva Guilherme Luz Torres Silva Michele de Souza Bastos Daniel Barros de Castro Monique Freire Santana Rajendranath Ramasawmy José Eduardo Levi Kátia Luz Torres Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. PLoS ONE |
| title | Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. |
| title_full | Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. |
| title_fullStr | Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. |
| title_full_unstemmed | Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. |
| title_short | Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon. |
| title_sort | presence of hpv with overexpression of p16ink4a protein and ebv infection in penile cancer a series of cases from brazil amazon |
| url | https://doi.org/10.1371/journal.pone.0232474 |
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