Analysis of human papillomavirus and Epstein-Barr virus infection and aberrant death-associated protein kinase methylation in high-grade squamous intraepithelial lesions

Lattario, Fernanda Ribeiro; Furtado, Yara; Fonseca, Renata; Silveira, Filomena Aste; Val, Isabel Chulvis do; Almeida, Gutemberg; Carvalho, Maria da Glória da Costa

doi:10.1111/j.1525-1438.2007.01060.x

Cited by 13 publications

(7 citation statements)

References 29 publications

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“…Of some significance may also be the presence of methylated regions of host regulatory gene promoters in cells infected with the HPV and EBV viruses (Kim et al, 2005;Lattario et al, 2008). The integration of high-risk human papillomavirus (HPV) into the host cell genome is one of the major contributing factors to cervical malignant transformation (Kulmala et al, 2006;Huang et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Herpesviruses as possible cofactors in HPV-16-related oncogenesis.

Szostek¹,

Zawilińska²,

Kopec³

et al. 2009

Acta Biochim Pol

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Cervical carcinogenesis is a complex problem with papillomavirus widely accepted as a causative agent. Integration of a human papillomavirus (HPV) of the high-risk type into the host cell genome is one of the major contributing factors to cervical malignant transformation. In this study, the correlation of CMV, EBV, HSV-1, HSV-2, HHV-6 and HHV-7 infections with the physical status of the HPV genome in cervical cancer and precancerous cervical lesions was investigated in sixty HPV-16-positive women. Cervical secretion samples were submitted to DNA extraction and analyzed by PCR. HPV-16 DNA was confirmed in genotyping with the reverse hybridization line probe assay. Multiplex PCR with specific primers for the E2/E6 genes was used to assess the viral integration status of HPV-16. Our results show that CMV DNA was more frequently present in samples with mixed forms of HPV-16 than in the episomal form (P < 0.025). Such a correlation was also observed in the case of EBV (P < 0.005). The presence of CMV resulted in a six-fold (OR 6.069; 95% CI 1.91-19.22; P = 0.002), while EBV caused a seven-fold (OR 7.11; 95% CI 1.70-29.67; P = 0.007) increase in the risk of the integrated or mixed HPV-16 genome occurrence. Our data suggest that coinfection with herpesviruses, especially CMV and EBV, may be involved in the integration of the HPV-16 genome and may contribute to the development of cervical cancer.

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Section: Resultsmentioning

confidence: 99%

Herpesviruses as possible cofactors in HPV-16-related oncogenesis.

Szostek¹,

Zawilińska²,

Kopec³

et al. 2009

Acta Biochim Pol

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“…The DNA extraction of the biopsy samples and cervical brushings was performed as described by Lattario et al (2008) [ 13 ]. Briefly, these samples were digested in 500 μL of solution containing 10 mM Tris-HCl, pH 7.5, 10 mM NaCl, 2% SDS, 10 mM EDTA, pH 8.0, and 15 μL 10 mg/mL proteinase K and incubated for 16 hours at 55°C, followed by phenol-chloroform (1:1) extraction.…”

Section: Methodsmentioning

confidence: 99%

Association between human papillomavirus and Epstein - Barr virus DNA and gene promoter methylation of RB1 and CDH1 in the cervical lesions: a transversal study

et al. 2015

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BackgroundHuman papillomavirus (HPV) inactivates the retinoblastoma 1 (RB1) gene by promoter methylation and reduces cellular E-cadherin expression by overexpression of DNA methyltransferase 1 (DNMT1). The Epstein-Barr virus (EBV) is an oncogenic virus that may be related to cervical carcinogenesis. In gastric cancer, it has been demonstrated that E-cadherin gene (CDH1) hypermethylation is associated with DNMT1 overexpression by EBV infection. Our aim was to analyze the gene promoter methylation frequency of RB1 and CDH1 and verify the association between that methylation frequency and HPV and EBV infection in cervical lesions.MethodsSixty-five samples were obtained from cervical specimens: 15 normal cervices, 17 low-grade squamous intraepithelial lesions (LSIL), 15 high-grade squamous intraepithelial lesions (HSIL), and 18 cervical cancers. HPV and EBV DNA testing was performed by PCR, and the methylation status was verified by MSP.ResultsHPV frequency was associated with cervical cancer cases (p = 0.005) but not EBV frequency (p = 0.732). Viral co-infection showed a statistically significant correlation with cancer (p = 0.027). No viral infection was detected in 33.3% (5/15) of controls. RB1 methylated status was associated with cancer (p = 0.009) and HPV infection (p = 0.042). CDH1 methylation was not associated with cancer (p = 0.181). Controls and LSIL samples did not show simultaneous methylation, while both genes were methylated in 27.8% (5/18) of cancer samples. In the presence of EBV, CDH1 methylation was present in 27.8% (5/18) of cancer samples. Only cancer cases presented RB1 promoter methylation in the presence of HPV and EBV (33.3%).ConclusionsThe methylation status of both genes increased with disease progression. With EBV, RB1 methylation was a tumor-associated event because only the cancer group presented methylated RB1 with HPV infection. HPV infection was shown to be significantly correlated with cancer conditions. The global methylation frequency was higher when HPV was present, showing its epigenetic role in cervical carcinogenesis. Nevertheless, EBV seems to be a cofactor and needs to be further investigated.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159157579149317.

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“…It is the etiologic agent of infectious mononucleosis (nonmalignant disorder) and is highly associated with several human malignancies, including the Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin diseases, gastric carcinoma, and breast cancer [4,5]. Epstein-Barr virus has been suggested as another oncogenic virus related to cervical carcinogenesis [6]. Previous studies demonstrated that cultured ectocervical epithelial cells can be infected with EBV and also showed an association between viral replication and epithelial differentiation [7,8].…”

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confidence: 98%