Preliminary Research On Clinical Screening Model Of Folate Receptor-mediated Cervical Special Dyeing(FRD)

Objective To evaluate and compare the diagnostic value and cost-effectiveness of different screening strategies of folic acid receptor mediated cervical special dyeing(FRD)in cervical lesion screening,and to explore a better diagnostic value and economical and feasible FRD screening model of cervical lesions,and to explore the effect of common infection of inferior genital tract and vaginal bleeding on FRD.Methods451 women were collected to screen cervical lesions,prospectively examined by FRD,HPV and TCT,in the first affiliated Hospital of Jinan University from June2017 to January 2019.1.The relationship between FRD and TCT and HPV was analyzed of 451 women.The diagnostic value of FRD testing alone and sequential screening of FRD-based screening were evaluated by taking the cervical biopsies of 174 women as the gold standard.2.The cost-effectiveness ratio was retrospectively analyzed and compared if 437 women were screened by six different screening strategies respectively(Strategy A: HPV triage when TCT is ASC-US.Strategy B: TCT triage for non-16 / 18 hr HPV-positive.Strategy C: TCT combined with HPV screening.Strategy D:TCT triage for FRD-suspicious,then HPV triage when TCT is ASC-US.Strategy E: HPV triage for FRD-suspicious,then TCT triage for non-16 / 18 hr HPV-positive.Strategy F: TCT combined with HPV triage for FRD-suspicious).3.To respectively compare that were there a statistically significant difference in the results of FRD of 451 women concomitant vaginal bleeding or not,and in the results of FRD of negative and positive of vaginal secretion pathogen examination plus BV test of 304 women,four items of STD of 57 women and vaginal secretion pathogen examination plus BV test plus four items of STD of52 women.Results1.Among the 451 women,the detection rate of ASC-H+ was 4.68%,9.57% and32.43% in the FRD-negative,FRD-suspicious and FRD-positive,respectively.And the detection rate of hr HPV was 25.75%,40.00% and 72.97%,respectively.There were significant differences between the above any two groups(P<0.05).The coincidence rate between FRD-negative and TCT combined with HPV screening was 86.62%,and the coincidence rate between FRD-positive and TCT combined HPV screening was 59.46%.2.The detection rate of HSIL(CIN2)+ was 6.25%,24.49% and79.31% in the FRD-negative,FRD-suspicious and FRD-positive,respectively.There were significant differences between the above any two groups(P<0.05).The diagnostic coincidence rate of FRD-negative and FRD-positive was 93.75% and79.31%,respectively.3.When FRD-suspicious was respectively classified as screening negateve and positive,the sensitivity was 56.10% and 86.05%,the specificity was 95.49% and67.67%,the positive predictive value was 79.31%% and 44.87%,the negative predictive value was 87.59% and 93.75%,the diagnostic coincidence rate was86.21% and 71.84%,the Youden index was 51.59% and 53.04%,the positive likelihood ratios was 12.44 and 2.64,the negative likelihood ratio was 0.46 and0.20,Kappa value was 0.57 and 0.49,respectively.The difference of sensitivity and specificity between the two situations are both statistically significant(P = 0.000).4.When FRD-suspicious was classified as screening negative,the sensitivity of FRD(56.10%)was not significantly different from TCT(48.78%)(P=0.648),but it was significantly lower than HPV(90.24%)(P=0.003),and the specificity of FRD(95.49%)was significantly higher than TCT(87.22%)and HPV(47.37%)(P<0.05).If FRD-suspicious was classified as screening positive,the sensitivity of FRD(85.37%)was not significantly different from HPV(90.24%)(P=0.727),but it was significantly higher than TCT(48.78%)(P=0.000).And the specificity of FRD(67.67%)was significantly lower than TCT(87.22%)and significantly higher than HPV(47.37%)(P<0.05).Meanwhile,AUC of FRD(0.84)was significantly different from AUC of TCT testing alone(0.70)and HPV testing alone(0.72)(P<0.05).5.The sensitivity of three sequential screening strategies of primary FRD screening with HPV or TCT or TCT in combination with HPV triage for FRD-suspicious was 85.37%,65.85% and 78.05%,respectively,and the specificity was 78.95%,90.23% and 84.21%.Compared with FRD testing alone,when FRD-suspicious was classified as screening negative,the sensitivities of three sequential screening strategies were both increased,but the specificities were decreased.When FRD-suspicious was classified as screening positive,the sensitivities of the three sequential screening strategies were both decreased,but the specificities were both increased.The AUC of the four FRD screening strategies(0.82,0.78,0.81 and 0.84,respectively)were not significantly different(P > 0.05).The Youden indexs of the three sequential screening strategies(0.66,0.58 and 0.64,respectively)were both higher than FRD.6.The sensitivities of three sequential screening strategies of primary FRD screening with HPV or TCT or TCT in combination with HPV triage for FRD-suspicious(85.37%,65.85%,and 78.05%,respectively)were not significantly different from TCT combined with HPV screening(78.05%)(P>0.05).But the specificities of the three sequential screening strategies(78.95%,90.23% and 84.21%,respectively)were both higher than that of TCT combined with HPV screening(64.66%)and the differences were both significant(P<0.05).There was a significant difference between AUC of primary FRD screening with HPV triage(0.82)and AUC of TCT combined with HPV screening(0.71)(P=0.048).While,the AUC of primary FRD screening with TCT triage(0.78)and primary FRD screening with TCT in combination with HPV triage(0.81)were not significantly different from TCT combined with HPV(0.71),and the differences of the three sequential screening strategies were not significant(P>0.05).Meanwhile,the sensitivity of TCT,HPV and TCT combined with HPV in the FRD-suspicious women was 33.33%,100.00% and 75.00%,respectively.And the AUC was 0.54,0.80 and 0.67,respectively.7.The cost-effectiveness ratio of strategie A,B,C,D,E and F was 6614.25,7103.10,9138.71,3841.71,3944.44 and 4506.18 yuan per case,respectively.The average number of visit in strategy D(1.47±0.81)was lower than that in strategy A(2.31 ±0.79),and the average number of visit in strategy E 1.57±0.98)was less than that in strategy B(2.60±0.99),and the average number of visit in strategy F(1.51±0.86)was lower than that in strategy C(2.38±0.79),the differences were both statistically significant(P=0.000).When the incremental cost-effectiveness ratio was used to compare the screening strategies,the strategy D’s incremental cost-effectiveness ratio was less 8357.48 yuan per positive case of cervical lesions than strategy A.And the strategy E’s incremental cost-effectiveness ratio was less 104026.00 yuan per positive case of cervical lesions than B.The number of positive cases of cervical lesions detected by strategy F was the same as that of strategy C,but the cost was obviously reduced.8.It could not be considered that the results of FRD between negative and positive of vaginal secretion pathogen examination plus BV test,four items of STD and Vaginal secretion pathogen examination plus BV test plus four items of STD was different,and there were not significant differences between them(P>0.05).The FRD grade of patients with vaginal bleeding(average rank 384.12)was higher than that of non-vaginal bleeding group(average rank 216.33),and the difference was statistically significant(P=0.000).Conclusions1.The color of FRD was darker,the detection rates of ASC-H+,hr-HPV + and HSIL(CIN2)+ were both higher,and the cervical lesions were more severe.2.The diagnostic coincidence rates of FRD-negative and FRD-positive were high,and the negative coincidence of FRD was 93.75%.The diagnostic value of FRD screening was obviously influenced by FRD-suspicious.While the negative predictive value of FRD testing alone was more than 85% and the diagnostic accuracy was slightly higher than that of TCT testing alone and HPV testing alone.3.The diagnostic value of FRD testing alone is obviously influenced by FRD-suspicious.But three sequential screening strategies of primary FRD screening with HPV or TCT or TCT in combination with HPV triage for FRD-suspicious could decrease the influence of FRD-suspicious in the diagnostic value of FRD and increase the Youden index.4.The sensitivities of three sequential screening strategies were both similar to that of TCT in combination with HPV screening(cotesting),but specificities were both slightly higher than that of cotesting.Meanwhile,the diagnostic accuracy of primary FRD screening with TCT or TCT in combination with HPV triage for FRD-suspicious was similar to that of cotesting,but the diagnostic accuracy of primary FRD screening with HPV triage for FRD-suspicious was slightly higher than that of cotesting.5.No matter it was primary HPV screening,primary TCT screening or cotesting,the average number of visit of primary FRD screening in addition to it was decrease,and the cost-effectiveness was better.6.It could not think that common lower genital tract infection had significant effect on the outcome of FRD,and vaginal bleeding increased the false positive rate of FRD.7.It is recommended that sequential screening mode of FRD-based screening,FRD-negative women entry into next round of screening,FRD-positive wowen direct referral to colposcopy,and FRD-suspicious women use HPV triage of high sensitivity.