Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis

BMC Cancer

Research Article

Carlos A Maestri¹  Newton S Carvalho²  Valentina Tarallo³  Chiara Grasso³  Morena Trevisan³  Laura De Marco³  Anna Gillio-Tos³  Daniela Zugna³  Hadriano M Lacerda³  Valentina Fiano³  Lorenzo Richiardi⁴  Franco Merletti⁴  Maria da Graça Bicalho⁵  Renata Slowik⁵  MarinaBarbaradeSousa Xavier⁵ 

[1] Department of Cervical Pathology, Hospital Erasto Gaertner, Curitiba, Brazil;Department of Gynecology and Obstetrics, Federal University of Paraná, Infectious Diseases in Gynecology and Obstetrics Sector, Hospital de Clínicas, Curitiba, Brazil;Department of Medical Sciences, Unit of Cancer Epidemiology – C.E.R.M.S, University of Turin, Turin, Italy;Department of Medical Sciences, Unit of Cancer Epidemiology – C.E.R.M.S, University of Turin, Turin, Italy;Centre for Oncologic Prevention, Turin, Italy;Laboratory of Immunogenetics and Hystocompatibility, Federal University of Paranà, Curitiba, Brazil;

关键词: HPV;    Cervical cancer;    HLA-G;    Methylation;   

DOI  :  10.1186/1471-2407-12-618

 received in 2012-07-10, accepted in 2012-12-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions.MethodsA case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression.ResultsHPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07).ConclusionsThis study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions.

【 授权许可】

CC BY   
© Gillio-Tos et al.; licensee BioMed Central Ltd. 2012