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Association between RASSF1A Promoter Hypermethylation and Oncogenic HPV Infection Status in Invasive Cervical Cancer: a Meta-analysis

  • Li, Jin-Yun (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Huang, Tao (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Zhang, Cheng (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Jiang, Dan-Jie (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Hong, Qing-Xiao (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Ji, Hui-Hui (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University) ;
  • Ye, Meng (The Affiliated Hospital, Ningbo University) ;
  • Duan, Shi-Wei (Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University)
  • Published : 2015.09.02

Abstract

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, $I^2=78%$). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, $I^2=55%$). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

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