AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION

Detalhes bibliográficos
Autor(a) principal: Carestiato, Fernanda Nahoum
Data de Publicação: 2013
Outros Autores: Afonso, Larissa Alves, Moyses, Natalia, Almeida Filho, Gutemberg Leao, Velarde, Luis Guillermo Coca, Cavalcanti, Silvia Maria Baeta
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Revista do Instituto de Medicina Tropical de São Paulo
Texto Completo: https://www.revistas.usp.br/rimtsp/article/view/78667
Resumo: SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.
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spelling AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION Padrão de metilação do gene P16INK4A e de infecções por HPV de alto risco acompanham a evolução de lesões cervicais SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer. RESUMO É reconhecido que infecções por papilomavírus humanos de alto risco (HPV) são causa necessária, mas não suficiente para o desenvolvimento do câncer cervical. Recentemente, estudos de silenciamento gênico apontaram que a hipermetilação do gene p16INK4A é importante co-fator para a carcinogênese cervical, eliminando a função supressora de tumor da proteína p16 em lesões malignas. Entretanto poucos estudos avaliaram a relação da metilação com a progressão da doença. Nosso objetivo foi investigar o padrão de metilação do gene P16INK4A em diferentes graus de lesão cervical e sua associação com a infecção por diferentes tipos de HPV. Nosso estudo de corte transversal avaliou 141 amostras cervicais de pacientes atendidas no Hospital Moncorvo Filho, Rio de Janeiro. A detecção e tipagem do HPV foi realizada pela técnica de reação em cadeia da polimerase (PCR), e a metilação do gene P16INK4A pela PCR-metilação específica em formato nested (MSP). A frequência de HPV foi de 62,4% (88/141). O tipo mais prevalente foi o HPV16 (37%), seguido pelo HPV18 (16,3%) e HPV33/45 (15,2%). Curva ascendente foi observada quanto ao padrão de metilação do gene P16INK4A e o grau da lesão: a metilação foi identificada em somente 10,7% das amostras de epitélio normal, em 22,9% das lesões de baixo grau, em 57,1% das lesões de alto grau e em 93,1% dos carcinomas (p < 0,0001). Foram feitas análises univariada e multivariada a fim de correlacionar metilação, idade, exposição ao tabaco, infecção e genótipo de HPV. Foi encontrada correlação da metilação com a infecção pelo HPV (p < 0,0001), genótipos de alto risco (p = 0,01), lesões de alto grau (p < 0,0007) e câncer (p < 0,0001). Uma vez que infecções pelo HPV e alterações epigenéticas mostraram forte associação estatística com o carcinoma cervical, sugerimos que estes padrões de metilação possam ser avaliados como potenciais biomarcadores, combinados à detecção dos HPV oncogênicos para identificação de pacientes em risco de câncer. Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo2013-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/rimtsp/article/view/78667Revista do Instituto de Medicina Tropical de São Paulo; Vol. 55 No. 5 (2013); 329-334Revista do Instituto de Medicina Tropical de São Paulo; Vol. 55 Núm. 5 (2013); 329-334Revista do Instituto de Medicina Tropical de São Paulo; v. 55 n. 5 (2013); 329-3341678-99460036-4665reponame:Revista do Instituto de Medicina Tropical de São Pauloinstname:Instituto de Medicina Tropical (IMT)instacron:IMTenghttps://www.revistas.usp.br/rimtsp/article/view/78667/82720Copyright (c) 2018 Revista do Instituto de Medicina Tropical de São Pauloinfo:eu-repo/semantics/openAccessCarestiato, Fernanda Nahoum Afonso, Larissa Alves Moyses, Natalia Almeida Filho, Gutemberg Leao Velarde, Luis Guillermo Coca Cavalcanti, Silvia Maria Baeta 2014-04-03T17:11:06Zoai:revistas.usp.br:article/78667Revistahttp://www.revistas.usp.br/rimtsp/indexPUBhttps://www.revistas.usp.br/rimtsp/oai||revimtsp@usp.br1678-99460036-4665opendoar:2022-12-13T16:52:14.486299Revista do Instituto de Medicina Tropical de São Paulo - Instituto de Medicina Tropical (IMT)true
dc.title.none.fl_str_mv AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
Padrão de metilação do gene P16INK4A e de infecções por HPV de alto risco acompanham a evolução de lesões cervicais
title AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
spellingShingle AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
Carestiato, Fernanda Nahoum
title_short AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
title_full AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
title_fullStr AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
title_full_unstemmed AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
title_sort AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION
author Carestiato, Fernanda Nahoum
author_facet Carestiato, Fernanda Nahoum
Afonso, Larissa Alves
Moyses, Natalia
Almeida Filho, Gutemberg Leao
Velarde, Luis Guillermo Coca
Cavalcanti, Silvia Maria Baeta
author_role author
author2 Afonso, Larissa Alves
Moyses, Natalia
Almeida Filho, Gutemberg Leao
Velarde, Luis Guillermo Coca
Cavalcanti, Silvia Maria Baeta
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Carestiato, Fernanda Nahoum
Afonso, Larissa Alves
Moyses, Natalia
Almeida Filho, Gutemberg Leao
Velarde, Luis Guillermo Coca
Cavalcanti, Silvia Maria Baeta
description SUMMARY High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant lesions (p < 0.0001). Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.
publishDate 2013
dc.date.none.fl_str_mv 2013-09-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/rimtsp/article/view/78667
url https://www.revistas.usp.br/rimtsp/article/view/78667
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/rimtsp/article/view/78667/82720
dc.rights.driver.fl_str_mv Copyright (c) 2018 Revista do Instituto de Medicina Tropical de São Paulo
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2018 Revista do Instituto de Medicina Tropical de São Paulo
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
publisher.none.fl_str_mv Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
dc.source.none.fl_str_mv Revista do Instituto de Medicina Tropical de São Paulo; Vol. 55 No. 5 (2013); 329-334
Revista do Instituto de Medicina Tropical de São Paulo; Vol. 55 Núm. 5 (2013); 329-334
Revista do Instituto de Medicina Tropical de São Paulo; v. 55 n. 5 (2013); 329-334
1678-9946
0036-4665
reponame:Revista do Instituto de Medicina Tropical de São Paulo
instname:Instituto de Medicina Tropical (IMT)
instacron:IMT
instname_str Instituto de Medicina Tropical (IMT)
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institution IMT
reponame_str Revista do Instituto de Medicina Tropical de São Paulo
collection Revista do Instituto de Medicina Tropical de São Paulo
repository.name.fl_str_mv Revista do Instituto de Medicina Tropical de São Paulo - Instituto de Medicina Tropical (IMT)
repository.mail.fl_str_mv ||revimtsp@usp.br
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