人乳头瘤病毒E6/E7mRNA检测在宫颈癌筛查中的意义

Significance of human papillomavirus E6/E7mRNA detection in cervical cancer screening

目的评估人乳头瘤病毒(HPV)E6/E7mRNA检测在宫颈癌筛查中的意义。方法对3 381名行机会性宫颈癌筛查的女性分别行液基细胞学(TCT)、HPV DNA及HPV E6/E7mRNA检查,其中371例结果可疑者行阴道镜下活检。分别记录其TCT、HPV DNA及HPV E6/E7mRNA检测结果及活检病理结果等,采用SPSS 19.0软件进行数据分析。结果人群筛查中HPV E6/E7mRNA的总阳性率为16.47%(557/3 381);炎症患者与宫颈上皮内瘤变(CIN)Ⅰ级患者HPV E6/E7mRNA的阳性率分别为60.73%(116/191)和68.60%(83/121),差异无统计学意义(F=1.98,P>0.05);炎症患者与CINⅠ级患者mRNA表达量分别为7 781.26±2 686.13和7 498.47±2 860.08 copy/m L,亦无显著差异(t=0.07,P>0.05),而CINⅡ-Ⅲ级患者HPV E6/E7mRNA的阳性率为89.10%(49/55),mRNA表达量为30 716.66±10 281.89,均显著高于炎症患者(χ2=15.55,t=2.19)及CINⅠ患者(χ2=8.47,t=2.18),差异均有统计学意义(P<0.05);不同活检病理分级(≤CINⅠ或≥CINⅡ)中,只有HPV E6/E7mRNA的检测结果有显著性差异(χ2=15.45,P<0.05);对于宫颈CINⅡ以上病变的诊断,HPV E6/E7mRNA的敏感度最高(89.83%);TCT特异度最高(62.18%)。HPV E6/E7mRNA最佳工作点为1 637.48copy/m L,其诊断宫颈高级别上皮内瘤变的敏感度为79.70%,特异度为63.50%。ROC曲线下面积为0.75(P<0.05)。结论 HPV E6/E7mRNA检测诊断宫颈高级别上皮内瘤变具有较高的敏感性和特异性,在宫颈癌筛查具有较为重要的意义。

Objective To evaluate the significance of human papillomavirus（ HPV） E6 /E7 mRNA detection in cervical cancer screening.Methods A total of 3 381 women who had taken an opportunistic cervical cancer screening received thin- prep cytologic test（ TCT）,HPV DNA and HPV E6 / E7 mRNA examinations. Among them,371 cases with suspicious results underwent colposcopy guided biopsy. The results of their TCT,HPV DNA and HPVE6 / E7 mRNA tests and the pathologic results were recorded and analyzed by SPSS19. 0 software.Results The total positive rate of the HPV E6 / E7 mRNA test was 16. 47%（ 557 /3 381）. The positive rate of HPV E6 / E7 mRNA in patients with inflammation and cervical intraepithelial neoplasia Ⅰ（ CIN Ⅰ） was 60. 73%（ 116 /191） and 68. 60%（ 83 /121）,respectively. The difference was not significant（ F = 1. 98,P〈0. 05）. The mRNA expression levels of patients with inflammation and patients with CIN Ⅰ was 7 781. 26 ± 2 686. 13 and 7 498. 47 ± 2 860. 08 copy / m L,respectively. The difference was also not significant（ t = 0. 07,P〈0. 05）. However,the positive rate and mRNA expression levels of CIN Ⅱ- Ⅲ patients（ 89. 10% [49 /55]; 30 716. 66 ±10 281. 89 copy / m L） were significantly higher than those of patients with inflammation（ χ2= 15. 55,t = 2. 19） and CIN Ⅰ patients（ χ2=8. 47,t = 2. 18）. The differences were all statistically significant（ all P〈0. 05）. Only HPV E6 / E7 mRNA test results were significantly different（ χ2= 15. 45,P〈0. 05） in patients with different biopsy grade（ ≤CIN Ⅰ or ≥CIN Ⅱ）. HPV E6 / E7 mRNA showed its highest sensitivity（ 89. 83%） while TCT had the highest specificity（ 62. 18%） in the diagnosis of CIN Ⅱ and above. The optimal operating point of HPV E6 / E7 mRNA was 1 637. 48 copy / m L. The sensitivity in diagnosing high degree of CIN lesions was 79. 70% and the specificity was63. 50%. The area under ROC curve was 0. 75（ P〈0. 05）. Conclusion HPV E6 / E7 mRNA test can detect and diagnose CIN lesions with relatively high sensitivity and specificity. Thus,it has important significance in cervical cancer screening.