高危型人乳头瘤病毒DNA阳性且伴有轻微细胞学异常的女性中，高危型人乳头瘤病毒mRNA的存在与未来高级别病变的关系
Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.
作者信息
Johansson Hanna, Bjelkenkrantz Kaj, Darlin Lotten, Dilllner Joakim, Forslund Ola
机构信息
Department of Laboratory Medicine, Medical Microbiology, Lund University, Malmö, Sweden.
Regional Cancer Centre South, Lund, Sweden.
出版信息
PLoS One. 2015 Apr 20;10(4):e0124460. doi: 10.1371/journal.pone.0124460. eCollection 2015.
OBJECTIVE
Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology.
METHODS
Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.
RESULTS
Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03).
CONCLUSION
The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade CIN.
目的
高危型人乳头瘤病毒（HPV）的E6和E7致癌基因的持续表达是发育异常表型发展和维持所必需的。本研究的目的是确定APTIMA HPV mRNA检测法（Hologic公司）在预测高危型HPV-DNA阳性且具有意义不明确的非典型鳞状细胞（ASCUS）或低度鳞状上皮内病变（LSIL）细胞学表现的女性未来发生高级别宫颈上皮内瘤变（CIN）方面的敏感性和特异性。
方法
对年龄≥35岁、高危型HPV DNA阳性的ASCUS（n = 211）或LSIL（n = 131）女性的存档SurePath宫颈样本，使用APTIMA HPV检测法检测高危型HPV E6/E7 mRNA的存在情况，并对这些女性进行组织病理学证实的CIN2+发展情况监测。
结果
ASCUS组29%（61/211）的女性和LSIL组34.3%（45/131）的女性在4.5年的随访期内发生了CIN2+。ASCUS女性中HPV mRNA的患病率为90.0%（95%CI 85.9 - 94.0），LSIL女性中为95.4%（95%CI 91.8 - 99.0）。HPV E6/E7 mRNA的存在与ASCUS和LSIL女性未来发生CIN2+相关（p = 0.02）。mRNA检测法在预测ASCUS（分别为96.7%；95%CI 87.6 - 99.4和100%；95%CI 82.2 - 100）和LSIL（97.8%，95%CI 86.8 - 99.9和100%，95%CI 79.9 - 100）未来的CIN2+和CIN3方面显示出高敏感性。对于未来的CIN2+，相应的特异性较低，分别为12.7%（95%CI 7.9 - 19.3）和5.8%（95%CI 2.2 - 13.6）。HPV mRNA检测法检测未来CIN3的阴性预测值为100%，因为与mRNA阳性女性的13.6%（43/315）相比，没有mRNA阴性的女性发生CIN3（0/27）（p = 0.03）。
结论
APTIMA mRNA检测法在预测细胞学轻度异常女性未来发生CIN2+方面显示出高敏感性但低特异性。该检测法对未来CIN3具有高阴性预测值，表明HPV-mRNA阴性的女性进展为高级别CIN的风险较低。
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