人乳头瘤病毒E6/E7 mRNA检测在宫颈癌筛查、分流中的价值分析

Value analysis of HPV E6∕E7 mRNA detection in cervical cancer screening and diversion

目的比较人乳头瘤病毒(HPV)E6/E7 mRNA与HPV-DNA分别及联合液基薄层细胞学检查(thin-prep cytology test,TCT)在宫颈病变筛查中的价值及HPV E6/E7 mRNA与HPV-DNA在非典型鳞状细胞(ASC-US)分流中的价值。方法纳入2022年1月~2023年12月于扬州大学医学院附属盐城妇幼保健院进行宫颈癌筛查的2079名受检者,行TCT、HPV-DNA、HPV E6/E7 mRNA检测,剔除3项结果均阴性者,513例行阴道镜活检。以病理报告为金标准,比较HPV-DNA和HPV E6/E7 mRNA的宫颈病变检出率。对HPV-DNA和HPV E6/E7 mRNA单独筛查及分别联合TCT筛查CIN2+(包括CIN2、CIN3及宫颈癌)的效能进行比较。对HPV-DNA与HPV E6/E7 mRNA分流ASC-US的效能进行比较。结果HPV-DNA CIN1检出率4.08%高于HPV E6/E7 mRNA的2.45%,差异有统计学意义(χ^(2)=8.787,P=0.003),而两种筛查方法CIN2+检出率差异无统计学意义(χ^(2)=0.250,P=0.617)。HPV-DNA和HPV E6/E7 mRNA筛查CIN2+的灵敏度为85.98%vs.81.09%、特异度为49.57%vs.84.24%,HPV-DNA的筛查灵敏度高于E6/E7 mRNA、特异度低于E6/E7 mRNA,两种筛查方法的特异度、阳性预测值及假阳性率差异有统计学意义(χ^(2)=94.732、32.802、94.732,P=0.000)。TCT联合HPV-DNA和TCT联合HPV E6/E7 mRNA筛查CIN2+的灵敏度为94.51%vs.90.85%、特异度为85.37%vs.90.26%,联合TCT提高了筛查的灵敏度和特异度,但TCT联合HPV-DNA的筛查特异度仍低于TCT联合HPV E6/E7 mRNA,两种联合筛查方法的特异度和假阳性率差异有统计学意义(χ^(2)=3.871、3.871,P=0.049)。HPV E6/E7 mRNA在ASC-US中筛查CIN2+的ROC曲线下面积为0.814,大于HPV-DNA的0.704,差异有统计学意义(χ^(2)=2.352,P<0.05)。结论与HPV-DNA相比,HPV E6/E7 mRNA单独筛查及分别与TCT联合筛查CIN2+均有更高的特异度,对ASC-US的分流管理更具优势。

Objective To compare the value of HPVE6∕E7 mRNA and HPV-DNA,respectively and in combination with TCT,in screening cervical lesions,and the value of E6∕E7 mRNA and HPV-DNA in ASC-US shunting.Methods 2079 women who underwent cervical cancer screening in our hospital from January 2022 to December 2023 were included in the study.TCT,HPV DNA,and HPV E6∕E7 mRNA tests were performed and those with negative results in all 3 categories were excluded.513 cases underwent vaginal biopsy.Using pathological reports as the gold standard,compare the positivity rates of HPV DNA and HPV E6∕E7 mRNA.Comparison of the efficacy of HPV DNA and HPV E6∕E7 mRNA screening alone and in combination with TCT screening for CIN2+(including CIN2,CIN3,and cervical cancer).Compare the efficiency of ASC-US for HPV DNA and HPV E6∕E7 mRNA diversion.Results The CIN1 rate in the HPV-DNA group was 4.08%,which higher than 2.45%in the E6∕E7 mRNA group(χ^(2)=8.787,P=0.003).There was no statistically significant difference in the CIN2+detection rate between the two screening methods(χ^(2)=0.250,P=0.617).The sensitivity and specificity of HPV-DNA and E6∕E7 mRNA in screening for CIN2+were 85.98%vs.81.09%and 49.57%vs.84.24%,respectively.The sensitivity of HPV-DNA screening was higher than that of E6∕E7 mRNA,while the specificity was lower than that of E6∕E7 mRNA.The differences in specificity,positive predictive value,and false positive rate between the two screening methods were statistically significant(χ^(2)=94.732,32.802,94.732,P=0.000).The sensitivity and specificity of TCT combined with HPV-DNA and TCT combined with E6∕E7 mRNA for screening CIN2+were 94.51%vs.90.85%and 85.37%vs.90.26%,respectively.The combination of TCT improved the sensitivity and specificity of screening,but the specificity of TCT combined with HPV-DNA was still lower than that of TCT combined with E6∕E7 mRNA.The difference in specificity and false positive rate between the two combined screening methods was statistically significant(χ^(2)=3.871,3.871,P=0.049).The area under the ROC curve of E6∕E7 mRNA in screening for CIN2+in ASC-US is 0.814,which is greater than that of HPV-DNA by 0.704,and the difference is statistically significant(χ^(2)=2.352,P<0.05).Conclusion Compared with HPV-DNA,E6∕E7 mRNA alone and in combination with TCT screening for CIN2+have higher specificity,and have more advantages in shunt management of ASC-US.