High-risk human papillomavirus (hrHPV)-based screening is becoming increasingly important, either by supplementing or replacing the traditional cytology-based cervical Pap smear. However, hrHPV screening lacks specificity, because it cannot differentiate between transient virus infection and clinically relevant hrHPV-induced disease. Therefore, reliable triage methods are needed for the identification of HPV-positive women with cervical intraepithelial neoplasia (CIN) in need of treatment. Promising tools discussed for the triage of these patients are molecular diagnostic tests based on epigenetic markers. Here, we compare the performance of two commercially available DNA methylation-based diagnostic assays—GynTect® and the QIAsure Methylation Test—in physician-taken cervical scrapes from 195 subjects. Both GynTect® and the QIAsure Methylation Test detected all cervical carcinoma and carcinoma in situ (CIS). The differences observed in the detection rates between both assays for the different grades of cervical lesions (QIAsure Methylation Test: CIN1 26.7%, CIN2 27.8% and CIN3 74.3%; GynTect®: CIN1 13.3%, CIN2 33.3% and CIN3 60%) were not significant. Concerning the false-positive rates, significant differences were evident. For the healthy (NILM) hrHPV-positive group, the false-positive rates were 5.7% for GynTect® and 26.4% for QIAsure Methylation Test (p = 0.003) and for the NILM hrHPV-negative group 2.2% vs. 23.9% (p = 0.006), respectively. When considering hrHPV-positive samples only for comparison (n = 149), GynTect® delivered significantly higher specificity compared to the QIAsure Methylation Test for CIN2 + (87.6% vs. 67.4% (p < 0.001)) and CIN3 + (84.1% vs. 68.2% (p = 0.002)). Overall our findings suggest that DNA methylation-based tests are suitable for the triage of hrHPV-positive women. With the goal to provide a triage test that complements the limited specificity of HPV testing in HPV-based screening, GynTect® may be preferable, due to its higher specificity for CIN2+ or CIN3+ .

中文翻译：

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hrHPV 阳性女性的分类：两种商业甲基化特异性 PCR 检测的比较

通过补充或替代传统的基于细胞学的子宫颈抹片检查，基于高危人乳头瘤病毒 (hrHPV) 的筛查变得越来越重要。然而，hrHPV 筛查缺乏特异性，因为它不能区分暂时性病毒感染和临床相关的 hrHPV 诱导疾病。因此，需要可靠的分类方法来识别需要治疗的宫颈上皮内瘤变 (CIN) HPV 阳性女性。讨论的对这些患者进行分类的有前景的工具是基于表观遗传标记的分子诊断测试。在这里，我们比较了两种商业上可用的基于 DNA 甲基化的诊断分析——GynTect® 和 QIAsure 甲基化测试——在医生采集的 195 名受试者的宫颈刮片中的性能。GynTect® 和 QIAsure 甲基化测试均检测到所有宫颈癌和原位癌 (CIS)。两种检测对不同级别宫颈病变（QIAsure 甲基化测试：CIN1 26.7%、CIN2 27.8% 和 CIN3 74.3%；GynTect®：CIN1 13.3%、CIN2 33.3% 和 CIN3 60%）的检出率的差异是不重要。关于假阳性率，显着差异是明显的。对于健康 (NILM) hrHPV 阳性组，GynTect® 的假阳性率为 5.7%，QIAsure 甲基化检测的假阳性率为 26.4% (p = 0.003)，而 NILM hrHPV 阴性组的假阳性率为 2.2% 与 23.9% (p = 0.006)，分别。当考虑仅用于比较的 hrHPV 阳性样本时 (n = 149)，与 CIN2 + 的 QIAsure 甲基化测试相比，GynTect® 提供了显着更高的特异性（87.6% 与 67.4%（p < 0. 001)) 和 CIN3 +（84.1% 对 68.2%（p = 0.002））。总体而言，我们的研究结果表明，基于 DNA 甲基化的测试适用于 hrHPV 阳性女性的分类。为了提供一种分类测试来补充 HPV 检测在基于 HPV 的筛查中的有限特异性，GynTect® 可能是更可取的，因为它对 CIN2+ 或 CIN3+ 具有更高的特异性。