title: The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis.
abstract: BACKGROUND
  Cervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN), and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power.
  
  
  METHODS
  We systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer.
  
  
  RESULTS
  Our results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54-36.06; cancer vs CIN: OR =2.53, 95% CI =1.79-3.5; CIN vs control: OR =9.68, 95% CI =5.82-16.02). The specificity, sensitivity, area under the receiver operating characteristic curve, and diagnostic odds ratio were 0.99 (95% CI: 0.97-0.99), 0.36 (95% CI: 0.28-0.45), 0.93 (95% CI: 0.91-0.95), and 43 (95% CI: 19-98), respectively.
  
  
  CONCLUSIONS
  Our findings indicate that abnormal CDKN2A methylation may be strongly correlated with the pathogenesis of cervical cancer. Our results also demonstrate that CDKN2A methylation might serve as an early detector of cervical cancer. These findings require further confirmation.
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University; Department of Medical Oncology, Affiliated Hospital, Ningbo University.
authors: Jinyun
authors: J
authors: Li
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University.
authors: Chongchang
authors: C
authors: Zhou
authors: Department of Molecular Diagnosis, Ningbo Diagnostic Pathology Center, Ningbo, Zhejiang, People's Republic of China.
authors: Haojie
authors: H
authors: Zhou
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University.
authors: Tianlian
authors: T
authors: Bao
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University.
authors: Tengjiao
authors: T
authors: Gao
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University.
authors: Xiangling
authors: X
authors: Jiang
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University; Department of Medical Oncology, Affiliated Hospital, Ningbo University.
authors: Meng
authors: M
authors: Ye
keywords: cervical cancer carcinogenesis; methylation; p16