The Role Of HrHPV E6E7 MRNA In Cervical Screening And Triage

Objective: To research hrHPVE6 / E7 mRNA performance in cervical cancer screening and triage effect for abnormal cytology results,explore the clinical value and feasibility in cervical screening.Methods: We chose 7791 women for opportunistic cervical cancer screening in Qingdao Municipal Hospital Group and Qingdao Chengyang People's Hospital gynecology clinic row from January 2013 to December 2015,between the ages of 21-65 years old.According to the cervical screening methods,patients were divided into three groups.Group A: thinprep cytology(LBC)+ hrHPV-DNA test(HC2 group);Group B:LBC + hrHPV-DNA genotyping test(HPV genotyping group);Group C: LBC + hrHPV E6 / E7 mRNA test(E6 / E7 group).We compared the accuracy of four screening methods,three cotesting strategies and cytology alone,including sensitivity,specificity,positive predictive value,negative predictive value,colposcopy referral rate,CIN2 + /CIN3 + detection rate.Results: 1.In E6E7 group,the HPV-positive rates of cytology results were NILM8.02%,ASCUS 47.80%,LSIL 58.86%,ASC-H 86.67%,HSIL 88.51%,respectively.The total HPV-positive rate was 14.73%.The difference was statistically significance(P trend<0.001).The HPV-positive rates of various cytology results and the total HPV-positive rate in E6E7 group were lower than the other two groups,the difference was statistically significant(P <0.05).2.The sensitivities of E6E7 detecting CIN2 + / CIN3 + were 93.02% and 94.83%,NPVs were 99.52% and 99.88%,without significant difference(P> 0.05)compared with HC2 and genotyping.The specificities of E6E7 detecting CIN2 +/CIN3 + were 90.20%and 86.90%,the differences were statistically significant compared with LBC,HC2 and genotyping in pair match(P <0.01).The PPV of E6E7 detecting CIN 2+ was 37.38%,higher than genotyping(P <0.01).When LBC as a reference,the RRs of E6E7 detecting CIN2 + / CIN3 + were 1.05(0.87-1.26),0.93(0.74-1.18),without significant difference.When HC2 and genotyping as references,the RRs of E6E7 detecting CIN2 + / CIN3 +were greater than 1,the differences were statistically significant.The colposcopy referral rate of E6E7 was 14.73%,which was lower than the other two HPV testand higher than the LBC,the differences were statistically significant(P <0.01).The CIN2 + / CIN3+detecting rates of three HPV tests were no significant difference(P> 0.05).3.The sensitivities,specificities,PPVs,NPVs,colposcopy referral rate,CIN2 + /CIN3 + detection rates of LBC + E6E7 for CIN2 + / CIN3 + were 91.28%(89.64%-93.97%),95.50%(94.76%-96.06%),56.07%(54.32%-58.84%),99.43%(98.32%-99.97%),9.64%,5.40%;and 93.10%(91.27%-95.03%),92.06%(91.58%-93.83%),19.29%(17.74%-22.21%),99.85%(98.67%-99.99%),9.64%,1.86%,respectively.These outcome index were not statistically different between three cotesting strategies(P> 0.05).4.The sensitivities for CIN2 + / CIN3 +of ASCUS triage by hrHPV E6 / E7 mRNA were 100.00%(90.51%-100.00%),specificities were 64.84%(53.06%-75.99%),56.46%(43.98%-69.72%),NPVs were 100.00%(99.41%-100.00%),100.00%(99.34%-100.00%),respectively,without significant difference(P> 0.05)compared with HC2 andgenotyping.PPVs were 40.79%(37.91%-44.29%),15.79%(10.07%-20.94%),higher than HC2(P <0.05).The colposcopy referral rate was 47.80%,lower than HC2 and genotyping,but without significant difference(P> 0.05).CIN2 + detection rate was19.50%,higher than HC2,the difference was statistically significant(P <0.05).5.The sensitivities for CIN2 + / CIN3 +of LSIL triage by hrHPV E6 / E7 mRNA were 70.83%(51.02%-89.14%),100.00%(81.19%-100.00%),specificities were 47.44%(28.18%-63.92%),46.32%(27.22%-64.31%),PPVs were 29.31%(19.51%-39.75%),12.07%(7.10%-17.36%),NPVs were 96.97%(86.39%-99.01%),100.00%(90.70%-100.00%).The colposcopy referral rate was56.86%.CIN2 +/CIN3+ detection rate was 16.67%,6.86%.The indicators of triage LSIL by hrHPV E6 / E7 mRNA were no significant difference compared with HC2 and genotyping(P> 0.05).6.The Kappa values of hrHPV E6 / E7 mRNA in CIN2 + / CIN3 + ??were 0.49 and 0.20,better than HC2 and genotyping consistency.In CIN2 +,the concordance rate between hrHPV E6E7 mRNA and HC2 was 82.64%,Kappa value was 0.69.hrHPV E6E7 m RNA loads were 687.54 ± 1209.59,1001.08 ± 1973.85,1499.90 ± 2934.18,3314.78 ±4480.08,14787.41 ± 19939.35 in normal biopsy,CIN1,CIN2,CIN3 and the ICC,respectively.mRNA load gradually increased with the aggravation of lesions,the difference was statistically significant(p trend <0.01).Conclusion:1.Compared with HC2 and genotyping,hrHPV E6E7 mRNA has the same sensitivity,higher specificity and lower colposcopy referral rate,the sameCIN2 + /CIN3 + detection rate so that it can be used for cervical screening.2.The sensitivity and specificity of ASCUS triage by hrHPV E6E7 mRNA is similar with HC2,with higherPPV and CIN2 + detection rate and lower colposcopy referral rate which is valuable in ASCUS triage.3.The accuracy of hrHPV E6E7 mRNA and LBC contesting is as well as HC2,HPV typing cotesting with LBC so that it could be an alternative as HPV-DNA in cotesting programm.4.The value of LSIL triage by hrHPV E6E7 m RNA has not been demonstrated,we need more clinical validation studies.5.The agreement between hrHPV E6E7 mRNA and HC2 in diagnosis of CIN2 + is good,and mRNA load increases with the severity of lesions which may reflect the degree of cervical lesions.