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

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrantmethylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. Thepurpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infectionin cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15studies. 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, I2=78%). By grouping cases according to cancer subtypes, we foundthat 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, I2=55%). Interestingly, HPVinfection 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 betweenHPV infection and RASSF1A promoter methylation in the development of cervical cancers.