Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, 450052, Henan Province, People's Republic of China.
Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Virol J. 2019 Nov 21;16(1):143. doi: 10.1186/s12985-019-1251-4.
We evaluated the prognostic and diagnostic ability of p16/Ki-67 immunocytochemistry, HPV E6/E7 mRNA testing and HPV DNA assay in triaging ASCUS to find a way to manage cervical lesions more effectively.
We conducted a prospective study through follow-up. The detection methods of the three factors: p16/Ki-67 immunocytochemistry conducted by using the CINtec® Plus Kit, E6/E7 mRNA testing by QuantiVirus®HPV E6/E7 mRNA assay and DNA by Hybrid Capture 2 assay.
One hundred three women with ASCUS satisfied requirements and completed the entire follow-up process. All CIN2+ occurred in women who were mRNA positive at baseline, none in mRNA negative. 100% (6/6) patients with CIN2+ were HPV DNA assay positive, 100% (6/6) were HPV E6/E7 mRNA testing positive and 50.0% (3/6) were p16/Ki-67 immunocytochemistry positive. The risk ratio of E6/E7 mRNA test was 57.306 (95% CI 0.077-42,400.545). For endpoint of CIN2+, the sensitivity between HPV DNA assay and HPV E6/E7 mRNA testing is no statistical difference, but statistical difference exists between HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry (χ = 5.718, P = 0.023) and HPV DNA assay vs. p16/Ki-67 immunocytochemistry (χ = 5.718, P = 0.023). The specificity of E6/E7 mRNA testing, p16/Ki-67 and DNA assay in triaging ASCUS was 44.33, 75.26 and 11.34% respectively and is all statistical difference (χ = 26.277, P < 0.001(HPV DNA assay vs. HPV E6/E7 mRNA testing), χ = 19.297, P < 0.001(HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry), χ = 80.707, P < 0.001(HPV DNA assay vs. p16/Ki-67 immunocytochemistry). The expression level of 2097.09 copies/ml was the optimal cut-off value for HPV E6/E7 mRNA testing to diagnose CIN2+, the sensitivity and specificity was 61.1 and 68.2%.
High expression of HPV E6/E7 mRNA could be a good candidate as a diagnostic biomarker to triage ASCUS superseding HPV DNA. p16/Ki-67 immunocytochemistry is suggested to be a good tool to triage ASCUS, but it reduced the sensitivity of diagnosis when improves the diagnostic specificity.
我们评估了 p16/Ki-67 免疫细胞化学、HPV E6/E7 mRNA 检测和 HPV DNA 检测在 ASCUS 患者分流中的预后和诊断能力，以寻找更有效地管理宫颈病变的方法。
我们通过随访进行了一项前瞻性研究。三种因素的检测方法：p16/Ki-67 免疫细胞化学采用 CINtec® Plus 试剂盒，E6/E7 mRNA 检测采用 QuantiVirus®HPV E6/E7 mRNA 检测，DNA 采用杂交捕获 2 检测。
103 名符合 ASCUS 要求并完成整个随访过程的女性。所有 CIN2+均发生在基线时 mRNA 阳性的女性中，mRNA 阴性的女性无一例发生。100%（6/6）CIN2+患者的 HPV DNA 检测阳性，100%（6/6）HPV E6/E7 mRNA 检测阳性，50.0%（6/6）p16/Ki-67 免疫细胞化学阳性。E6/E7 mRNA 检测的风险比为 57.306（95%CI 0.077-42,400.545）。对于 CIN2+的终点，HPV DNA 检测与 HPV E6/E7 mRNA 检测的敏感性无统计学差异，但 HPV E6/E7 mRNA 检测与 p16/Ki-67 免疫细胞化学检测（χ²=5.718，P=0.023）和 HPV DNA 检测与 p16/Ki-67 免疫细胞化学检测（χ²=5.718，P=0.023）存在统计学差异。E6/E7 mRNA 检测、p16/Ki-67 和 DNA 检测在 ASCUS 患者分流中的特异性分别为 44.33%、75.26%和 11.34%，均有统计学差异（χ²=26.277，P<0.001（HPV DNA 检测与 HPV E6/E7 mRNA 检测相比），χ²=19.297，P<0.001（HPV E6/E7 mRNA 检测与 p16/Ki-67 免疫细胞化学检测相比），χ²=80.707，P<0.001（HPV DNA 检测与 p16/Ki-67 免疫细胞化学检测相比）。HPV E6/E7 mRNA 检测的最佳截断值为 2097.09 拷贝/ml，用于诊断 CIN2+，其敏感性和特异性分别为 61.1%和 68.2%。
HPV E6/E7 mRNA 的高表达可作为 ASCUS 患者分流的一种良好候选诊断生物标志物，取代 HPV DNA。p16/Ki-67 免疫细胞化学是一种很好的 ASCUS 患者分流工具，但当提高诊断特异性时，会降低诊断的敏感性。
