Validation of a DNA methylation HPV triage classifier in a screening sample.
Validation of a DNA methylation HPV triage classifier in a screening sample.
复制标题
筛选样品中DNA甲基化HPV分类器分类器的验证。
DOI：
10.1002/ijc.30008
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发表时间：
2016-06-01
影响因子：
6.4
通讯作者：
Vasiljević N
中科院分区：
文献类型：
--
作者：
Lorincz AT;Brentnall AR;Scibior-Bentkowska D;Reuter C;Banwait R;Cadman L;Austin J;Cuzick J;Vasiljević N
高危型人乳头瘤病毒（hrHPV）DNA检测对于检测宫颈上皮内瘤变2或更高（CIN 2+）具有极好的灵敏度。然而，hrHPV筛查的缺点是特异性不高。因此，hrHPV阳性的女性可能需要分诊，以减少不良事件和与不必要的阴道镜检查相关的费用。我们比较了HPV 16/18基因分型与基于人类基因EPB 41 L3的靶区域以及HPV 16、HPV 18、HPV 31和HPV 33的病毒晚期基因区域的预定义DNA甲基化分类测试（S5）的性能。使用来自710名参加常规筛查的妇女的宫颈脱落标本进行检测，其中38名在基于细胞学的阴道镜检查分类后一年内被诊断为CIN 2+，341名为hrHPV阳性。通过McNemar检验比较了所研究的分诊方法的灵敏度和特异性。在预定的临界值，S5在识别hrHPV阳性女性的CIN 2+方面显示出比HPV 16/18基因分型更好的灵敏度（74% vs 54%，P = 0.04），以及相似的特异性（65% vs 71%，P = 0.07）。当改变S5临界值以使其与基因分型的敏感性相等时，特异性显著更高，达到91%（P < 0.0001）。因此，在原始筛查标本上对hrHPV阳性女性进行分诊的DNA甲基化检测可能是一种有效的方法，其性能优于基因分型。 有什么新消息吗？ 高危人乳头瘤病毒（hrHPV）的DNA检测可以检测和预测宫颈癌前病变的发展。然而，由于特异性的局限性，有必要制定分诊策略，以尽量减少hrHPV阳性女性中不必要的阴道镜检查。根据这项研究，使用基于人类基因EPB 41 L3和HPV 16、HPV 18、HPV 31和HPV 33的晚期基因区域的DNA甲基化分类器可以容易地影响分诊。设计的分类器在hrHPV阳性患者队列中通过HPV 16/18基因分型优于分诊。该策略可以在宫颈筛查项目中的hrHPV分诊中发挥关键作用。
High‐risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV‐positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV‐positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV‐positive women on original screening specimens might be a valid approach with better performance than genotyping. What's new? DNA testing for high‐risk human papillomaviruses (hrHPVs) can both detect and predict the development of precancerous cervical lesions. Limitations in specificity, however, necessitate the generation of triage strategies to minimize unneeded colposcopy among hrHPV‐positive women. According to this study, triage may be readily affected using a DNA methylation classifier based on the human gene EPB41L3 and the late gene regions of HPV16, HPV18, HPV31 and HPV33. The devised classifier outperformed triage by HPV16/18 genotyping in a cohort of hrHPV‐positive patients. The strategy could fill a key role in hrHPV triage in cervical screening programs.