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Title
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Using the VALGENT-3 framework to assess the clinical and analytical performance of the RIATOL qPCR HPV genotyping assay
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Journal of clinical virology. - Rome
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Journal of clinical virology (Print)
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Publication
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Rome
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2019
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ISSN
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1386-6532
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DOI
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10.1016/J.JCV.2019.09.008
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Volume/pages
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120
(2019)
, p. 57-62
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ISI
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000491873600011
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Full text (Publisher's DOI)
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Full text (open access)
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