| Objective:With different screening populations as the starting point and cervical biopsy results as the gold standard,this study aims to evaluate the clinical application value of HPV E6/E7 mRNA detection in the diagnosis of high-grade cervical lesions in different populations,and provide a theoretical basis for more efficient screening of high-grade cervical lesions.Methods:This study selected different screening populations as research objects,including outpatient opportunistic screening populations and census populations.(1)Opportunistic screening population: A total of 1,409 patients who were admitted to the gynecological clinic of our hospital from March 2021 to December 2022 and met the NA standard were selected.All patients underwent thin-layer liquid-based cytology(TCT),HPV DNA detection(including HC2 detection or high-risk HPV detection)and HPV E6/E7 mRNA detection(hereinafter referred to as mRNA detection).(2)The population of the census were selected from 3,000 women who met the standard of natrexia in Shuangjiang Maternal and Child Health Hospital,Lincang City,Yunnan Province from January 2022 to December 2022.All the women underwent TCT and mRNA detection.According to colposcopy referral guidelines,biopsy results were the gold standard,the consistency of mRNA detection and HPV DNA detection was compared,and the detection rate and colposcopy referral rate of high-grade cervical lesions with different screening methods and different shunt strategies were statistically analyzed.The sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Yoden index and AUC value were calculated.Results:1.Consistency analysis of HPV E6/E7 mRNA detection and HPV DNA detection: In different histropathological grades of the opportunistic screening population,Kappa coefficients of the two groups were successively as follows: cancer group 1.0,LSIL group 0.945,HSIL group 0.833,inflammation group 0.088,and overall 0.533.The consistency between the two groups was the highest in the cancer group,and the consistency was good in the LSIL and HSIL groups,and the consistency was general.Therefore,mRNA detection could be expected to be the primary screening method for high-grade cervical lesions.2.Positive rate of HPV E6/E7 mRNA detection in different histopathologic grades:(1)1409 cases of opportunistic screening population: 922 cases of chronic inflammation,230 cases of LSIL,216 cases of HSIL,41 cases of cervical cancer(40cases of squamous cell carcinoma,1 case of adenocarcinoma).mRNA positive rates were 26.3% and 91.6% in patients with ≤LSIL and ≥HSIL respectively.(2)There were 3000 cases: 2885 cases of chronic inflammation,82 cases of LSIL,31 cases of HSIL,1 case of cervical cancer;The positive rates of mRNA were 4.9% and 90.9% in patients with ≤LSIL and ≥HSIL,respectively.By binary Logistic regression analysis,mRNA detection positive rates of ≤LSIL and ≥HSIL were significantly correlated between the two groups(P < 0.001).3.Comparison of the efficacy of different preliminary screening methods in detecting high-grade cervical lesions in the opportunistic screening population:Sensitivity,specificity,positive predictive value,Yoden index and AUC values of the six preliminary screening methods in diagnosing lesions ≥HSIL were in order: mRNA(91.4%,73.7%,43.7%,0.651,0.826),DNA(96.9%,48.7%,29.6%,0.456,0.728),TCT(51.8%,88.8%,50.8%,0.406,0.703),TCT+ mRNA(49%,94.1%,64.9%,0.431,0.716),TCT+DNA(50.2%,90.6%,54.4%,0.408,0.704),TCT+DNA+ mRNA(47.5%,94.3%,64.9%,0.417,0.709);The Yoden index and AUC values of mRNA preliminary screening were the highest,and the differences between mRNA and AUC of other 5 preliminary screening methods were statistically significant(P < 0.05).4.Comparison of the efficacy of different shunt strategies in the opportunistic screening population: Among the four shunt strategies,the number of colposcopy referrals/cases of diagnosis of high-grade and above lesions,Yoden index and AUC value were: TCT+DNA→mRNA(577/240,0.641,0.821),TCT+(using TCT combined DNA as primary screening,mRNA as shunt)mRNA→DNA(577/240,0.641,0.821),TCT→mRNA shunt(220/131,0.433,0.716),mRNA→TCT shunt(194/126,0.431,0.716),The efficiency of the first two shunt strategies was almost the same as that of TCT+DNA screening alone and TCT+ mRNA screening alone.Nearly half of the cases ≥HSIL were missed by mRNA→TCT shunt compared with the initial screening of mRNA alone.Although the sensitivity of TCT→mRNA shunt decreased slightly(51%vs51.8%),the specificity and AUC value increased significantly(92.3% vs 88.8%;0.716 vs 0.703),the diagnostic efficacy was better than that of single TCT preliminary screening,and the TCT→mRNA shunt efficacy was considered to be the best.5.Comparison of the efficacy of different screening methods in detecting high-grade cervical lesions in the general population: the sensitivity,specificity,positive predictive value,Yoden index and AUC values of the three screening methods in diagnosing lesions ≥HSIL are as follows: mRNA(90.9%,95.1%,17%,0.86,0.930),TCT(42.4%,94.4%,7.7%,0.368,0.691),TCT+mRNA(33.3%,98.5%,19.6%,0.318,0.659);The Yoden index and AUC values of mRNA preliminary screening were the highest,and the results of mRNA preliminary screening were statistically different from those of TCT and TCT+mRNA combined preliminary screening(P < 0.05).6.Comparison of the efficacy of different shunt strategies in the general population:Among the three shunt strategies,the number of colposcopy referrals/cases of diagnosis of high-grade and above lesions,Yoden index and AUC value were successively: TCT→mRNA shunt(56/11,0.318,0.659),mRNA→TCT(76/14,0.403,0.702),TCT+ mRNA mainly shunt(120/19,0.627,0.813).The three shunt strategies all required referral of 5-6 women for colposcopy for every case ≥HSIL detected.However,comprehensive analysis showed that compared with the other two shunt strategies,the TCT→mRNA shunt did not miss too many patients with high-grade lesions,and fewer people were referred for colposcopy.It is also believed that TCT→mRNA has the best shunt effect.Conclusion:1.In different histopathologic grades,the overall consistency between mRNA detection and DNA detection in the opportunistic screening population was general,and the consistency was the highest in the cancer group,while the consistency was better in the LSIL and HSIL groups.mRNA detection could be expected to be the primary screening method for high-grade cervical lesions.2.The positive rate of HPV E6/E7 mRNA increased with the increase of cervical pathological grade.3.HPV E6/E7 mRNA has the best diagnostic efficacy for lesions ≥HSIL,which is expected to be a candidate for cervical cancer screening tool;The efficacy of opportunistic screening TCT+mRNA co-test is better than that of TCT+DNA co-test,which can be used as an alternative to cervical cancer screening co-test.4.In opportunistic screening or census population,using TCT as initial screening and mRNA as shunt(TCT→mRNA)may be a feasible triage strategy. |
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