BACKGROUND AND OBJECTIVE The VALGENT framework is developed to assess the clinical performance of HPV tests that offer genotyping capability. Samples from the VALGENT-3 panel are used to identify an optimal viral concentration threshold for the RIATOL qPCR HPV genotyping assay (RIATOL qPCR) to assure non-inferior accuracy to detect high-grade cervical intraepithelial neoplasia (CIN), compared to Qiagen Hybrid Capture 2 (HC2), a standard comparator test validated for cervical cancer screening. STUDY DESIGN The VALGENT-3 panel comprised 1300 samples from women participating in the Slovenian cervical cancer screening programme, enriched with 300 samples from women with abnormal cytology. In follow- up, 126 women were diagnosed with CIN2+ (defined as diseased) and 1167 women had two consecutive negative Pap smears (defined as non-diseased). All 1600 samples were analyzed with the RIATOL qPCR. Viral concentration was expressed as viral log10 of the number of copies/ml. A zone of viral concentration cut-offs was defined by relative ROC analysis where the sensitivity and specificity were not inferior to HC2. RESULTS The RIATOL qPCR had a sensitivity and specificity for CIN2+ of 97.6% (CI: 93.2-99.5%) and 85.1% (CI: 82.9-87.1%), respectively, when the analytical cut off was used. At a cut off of 6.5, RIATOL qPCR had a sensitivity of 96.0% (CI: 91.0-98.7%) and a specificity of 89.5% (87.6-91.2%). At optimized cut off, accuracy of the qPCR was non-inferior to the HC2 with a relative sensitivity of 1.00 [CI: 0.95-1.05 (p = 0.006)] and relative specificity of 1.00 [CI: 0.98-1.01 (p = 0.0069)]. CONCLUSIONS The RIATOL qPCR has a high sensitivity and specificity for the detection of CIN2 + . By using a fixed cut-off based on viral concentration, the test is non-inferior to HC2. HPV tests that provide viral concentration measurements or other quantifiable signals allow flexibility to optimize accuracy required for cervical cancer screening.

中文翻译：

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使用VALGENT-3框架评估RIATOL qPCR HPV基因分型测定的临床和分析性能。

背景和目的VALGENT框架旨在评估提供基因分型能力的HPV检测的临床表现。与Qiagen Hybrid Capture相比，来自VALGENT-3小组的样品用于确定RIATOL qPCR HPV基因分型测定（RIATOL qPCR）的最佳病毒浓度阈值，以确保检测劣质宫颈上皮内瘤样病变（CIN）的准确性不差2（HC2），经过验证可用于宫颈癌筛查的标准比较剂测试。研究设计VALGENT-3小组包括1300名来自斯洛文尼亚宫颈癌筛查计划的女性样本，并丰富了300名细胞学异常女性的样本。在随访中，有126名妇女被诊断出患有CIN2 +（定义为患病），有1167名妇女连续两次出现了阴性的子宫颈抹片检查（定义为未患病）。用RIATOL qPCR分析了所有1600个样品。病毒浓度表示为拷贝数/ ml的病毒log10。通过相对ROC分析确定了病毒浓度截止的区域，其中敏感性和特异性均不逊于HC2。结果当使用分析截止值时，RIATOL qPCR对CIN2 +的敏感性和特异性分别为97.6％（CI：93.2-99.5％）和85.1％（CI：82.9-87.1％）。截止值为6.5时，RIATOL qPCR的灵敏度为96.0％（CI：91.0-98.7％），特异性为89.5％（87.6-91.2％）。在优化的截止值下，qPCR的准确性不亚于HC2，相对灵敏度为1.00 [CI：0.95-1.05（p = 0.006）]，相对特异性为1.00 [CI：0.98-1.01（p = 0.0069） ]。结论RIATOL qPCR对CIN2 +的检测具有很高的灵敏度和特异性。通过使用基于病毒浓度的固定截止值，该测试不劣于HC2。提供病毒浓度测量或其他可量化信号的HPV检测可灵活地优化子宫颈癌筛查所需的准确性。