The Role Of Dna Hypermethylation Of DapkⅠ And Rarβ Combined With High-risk Type Hpv In Early Diagnosis Of Cervical Cancer And Precursor Lesions

Objective: In the current study, we examined the role of aberrant methylation of DAPKⅠand RARβin the devlopment of cervical neoplasm and the significance of united detection of hypermethylation of the above two-genes coupled with high-risk type HPV in the early diagnosis of cervical neoplasm.Method: The exfoliated cells of 48 patients of chronic cervicitis,28 patients of CIN,28 patients of invasive cervical cancer were studied.These samples were collected from out-patients and in-patients at the Affiliated Hospital of Nantong University.All specimens were performed with MSP and HPV type-differentia detection.The hypermethylation of the two genes and HPV infection of these patients were examined. Combining with the TCT results of these patients,we compared the differences of sensitivity and specificity to various stages of cervical lesion with defferent screening method.Results:The hypermethylation rates of DAPKⅠin patients of chronic cervitis, CINⅠ/CINⅡ, CINⅢ/CIS and ICC were 2.08%,14.28%,50.00% and 60.71% respectively.The sensitivity, specificity, positive predictive value(PPV)and negative predictive value(NPV) of DAPKⅠto the invasive cervical cancer were 60.71%,86.84%,62.96% and 85.71% respectively.And to cervical cancer and its precursor lesions, the sensitivity, specificity, PPV and NPV were 46.43%,97.92%, 96.30% and 61.04%. The hypermethylation rates of RARβin patients of chronic cervitis, CINⅠ/CINⅡ, CINⅢ/CIS and ICC were 4.55%, 7.69%, 42.86% and 53.57%. The detection showed the sensitivity, specificity, PPV and NPV to the invasive cervical cancer of 53.57%, 87.67%, 62.50% and 83.12%,while in cervical cancer and its precursor lesions those indicators were 40%, 5.65%, 91.67% and 57.14%.The infection rates of high-risk HPV in patients of chronic cervitis, CINⅠ/CINⅡ, CINⅢ/CIS and ICC were 33.33%, 50.00%, 71.43% and 89.29%. The HPV test showed the sensitivity, specificity, PPV and NPV of 60.71%, 86.84%, 62.96% and 85.71% to the invasive cervical cancer ,and to cervical cancer and its precursor lesions the digital quantity were 46.43%, 97.92%, 96.30% and 61.04%.Detection of the aberrant methylation of the two genes combined with the HPV test in screening invasive cervical cancer showed the sensitivity, specificity, PPV and NPV of 96.43%, 93.11%, 81.82% and 98.59%,and of 82.14%, 100%, 100% and 82.76% when screening cervical cancer and its percursor lesions.Conclution:The aberrant methylation of DAPKⅠand RARβcan be detected in chronic cervitis,CIN and invasive cervical cancer(ICC)with increasing rate. The methylation analysis of DAPKⅠcombined with RARβin screening of cervical cancer was of high specificity and was also superior to methylation detection of single gene in sensitivity of screening.This method was expected to be clinically useful for detection or stratification of ICC and/or its precursor lesions with high sensitivity and specificity. United screening metods of single-gene hypermethylation detection,HPV detection and thinprep cytologic test was more effective compared with the unitary screening technique.The study showed that detection of two-genes hypermethylation combined with HPV was of the highest sensitivity and specificity and was supposed to be the best candidate to screen cervical cancer.