Zhang Shao-Kai, Guo Zhen, Wang Peng, Kang Le-Ni, Jia Man-Man, Wu Ze-Ni, Chen Qiong, Cao Xiao-Qin, Zhao Dong-Mei, Guo Pei-Pei, Sun Xi-Bin, Zhang Jian-Gong, Qiao You-Lin
Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Central Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Front Oncol. 2020 Oct 2;10:533253. doi: 10.3389/fonc.2020.533253. eCollection 2020.
This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7-96.4) and 95.7% (95%CI: 91.3-97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), but higher than LBC (80.4% [95%CI: 74.5-85.2] and 88.8% [95%CI: 83.0-92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2-83.0]) and CIN3+ (70.5% [95%CI: 65.7-74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), but lower than LBC (84.5% [95%CI: 80.1-88.0] 79.8% [95%CI: 75.4-83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.
本研究旨在评估人乳头瘤病毒（HPV）E6/E7信使核糖核酸（mRNA）检测在中国宫颈癌筛查中的临床性能。开展了一项基于医院的研究，将mRNA、脱氧核糖核酸（DNA）和液基细胞学检查（LBC）作为主要筛查检测方法。每个检测结果呈阳性的女性均接受了针对病变的靶向活检的阴道镜检查。组织病理学诊断被用作金标准。HPV DNA和mRNA的总体一致性为90.7%（95%置信区间：87.9, 92.9），kappa值为0.81。HPV DNA、mRNA和LBC的阳性率随着组织病理学诊断的严重程度增加，从正常情况下的25.5%、19.1%和11.4%分别增加到鳞状细胞癌（SCC）中的100.0%。mRNA检测宫颈上皮内瘤变2级及以上（CIN2+）和宫颈上皮内瘤变3级及以上（CIN3+）的敏感度分别为93.8%（95%置信区间：89.7 - 96.4）和95.7%（95%置信区间：91.3 - 97.9），与HPV DNA检测（95.7% [95%置信区间：92.0 - 97.7]，96.3% [95%置信区间：92.1 - 98.3]）无差异，但高于LBC（80.4% [95%置信区间：74.5 - 85.2]和88.8% [95%置信区间：83.0 - 92.8]）。mRNA检测CIN2+（79.0% [95%置信区间：74.2 - 83.0]）和CIN3+（70.5% [95%置信区间：65.7 - 74.9]）的特异度高于HPV DNA检测（71.0% [95%置信区间：65.9 - 75.7]，62.8% [95%置信区间：57.8 - 67.5]），但低于LBC（84.5% [95%置信区间：80.1 - 88.0]，79.8% [95%置信区间：75.4 - 83.6]）。所有检测方法对30岁以上女性更有效。HPV mRNA检测与DNA检测显示出极佳的一致性，在检测高级别宫颈病变方面具有相似的敏感度和更高的特异度。mRNA检测有望用于全国宫颈癌筛查，以减少假阳性且不降低敏感度。
