Introduction:Effective detection methods to distinguish between transient human papillomavirus(HPV)infection and clinically relevant high-risk HPV(hrHPV)-induced diseases are lacking,leading to excessive referrals and...Introduction:Effective detection methods to distinguish between transient human papillomavirus(HPV)infection and clinically relevant high-risk HPV(hrHPV)-induced diseases are lacking,leading to excessive referrals and overtreatment.This study evaluated the clinical performance of a host DNA sixmethylation marker panel(ASTN1,DLX1,ITGA4,RXFP3,SOX17,and ZNF671)to triage Chinese women who were hrHPV-positive.Methods:This prospective multicenter study enrolled women aged 21-65 years with positive hrHPV testing.hrHPV genotyping,cytology,colposcopy,and the six-methylation marker assay were performed.High-grade cervical lesions were defined as histologically confirmed CIN2+.Forest plots analyses were performed to assess the triage performance of the methylation assay.Results:Of the 1,806 patients recruited from 4 hospitals in China,1,659 were included.The methylation assay positivity rates were 7.5%,73.9%,88.9%,and 100%for CIN1,CIN2,CIN3,and cervical cancer,respectively.The six-methylation marker assay demonstrated sensitivities of 82.2%and 90.3%and specificities of 92.4%and 84.1%for CIN2+and CIN3+,respectively,which were higher than those of HPV genotype testing and cytology(≥ASCUS)screening;the areas under the curve for CIN3+detection were 0.87(0.84-0.90),0.68(0.64-0.72),and 0.64(0.60-0.69),respectively.The six-methylation marker assay showed the lowest colposcopy referral rate(24.2%)and required the fewest referrals for detection,with 1.32 and 2.39 referrals per CIN2+and CIN3+cases,respectively.In women aged<30 years,the six-methylation marker assay had the highest specificity for CIN2+(95.7%)and a sensitivity and specificity for CIN3+of 80.8%and 88.9%,respectively.It had the lowest referral rate(17.17%)and colposcopy referrals,with 1.24 and 2.43 per CIN2+and CIN3+cases,respectively.Conclusions:The host DNA six-methylation marker assay is a reliable triage tool for women who are hrHPV-positive,providing evidence supporting the application of methylation markers in China.展开更多
文摘Introduction:Effective detection methods to distinguish between transient human papillomavirus(HPV)infection and clinically relevant high-risk HPV(hrHPV)-induced diseases are lacking,leading to excessive referrals and overtreatment.This study evaluated the clinical performance of a host DNA sixmethylation marker panel(ASTN1,DLX1,ITGA4,RXFP3,SOX17,and ZNF671)to triage Chinese women who were hrHPV-positive.Methods:This prospective multicenter study enrolled women aged 21-65 years with positive hrHPV testing.hrHPV genotyping,cytology,colposcopy,and the six-methylation marker assay were performed.High-grade cervical lesions were defined as histologically confirmed CIN2+.Forest plots analyses were performed to assess the triage performance of the methylation assay.Results:Of the 1,806 patients recruited from 4 hospitals in China,1,659 were included.The methylation assay positivity rates were 7.5%,73.9%,88.9%,and 100%for CIN1,CIN2,CIN3,and cervical cancer,respectively.The six-methylation marker assay demonstrated sensitivities of 82.2%and 90.3%and specificities of 92.4%and 84.1%for CIN2+and CIN3+,respectively,which were higher than those of HPV genotype testing and cytology(≥ASCUS)screening;the areas under the curve for CIN3+detection were 0.87(0.84-0.90),0.68(0.64-0.72),and 0.64(0.60-0.69),respectively.The six-methylation marker assay showed the lowest colposcopy referral rate(24.2%)and required the fewest referrals for detection,with 1.32 and 2.39 referrals per CIN2+and CIN3+cases,respectively.In women aged<30 years,the six-methylation marker assay had the highest specificity for CIN2+(95.7%)and a sensitivity and specificity for CIN3+of 80.8%and 88.9%,respectively.It had the lowest referral rate(17.17%)and colposcopy referrals,with 1.24 and 2.43 per CIN2+and CIN3+cases,respectively.Conclusions:The host DNA six-methylation marker assay is a reliable triage tool for women who are hrHPV-positive,providing evidence supporting the application of methylation markers in China.
