Using the VALGENT-3 framework to assess the clinical and analytical performance of the RIATOL qPCR HPV genotyping assay

•Cervical cancer screening with HPV tests should use only clinically validated assays.•Clinical performance of RIATOL qPCR HPV genotyping assay was validated using cut-off defined in terms of viral concentration for the first time.•HPV tests which produce quantified results in terms of viral concent...

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Bibliographic Details
Published in:Journal of clinical virology 2019-11, Vol.120, p.57-62
Main Authors: Benoy, I., Xu, L., Vanden Broeck, D., Poljak, M., Oštrbenk Valenčak, A., Arbyn, M., Bogers, J.
Format: Article
Language:English
Subjects:
Cervical cancer
HPV genotyping
Human papillomavirus
Test validation
VALGENT
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Summary:•Cervical cancer screening with HPV tests should use only clinically validated assays.•Clinical performance of RIATOL qPCR HPV genotyping assay was validated using cut-off defined in terms of viral concentration for the first time.•HPV tests which produce quantified results in terms of viral concentrations or other quantifiable signals allow flexibility to optimize the clinical accuracy required for primary cervical cancer screening. 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. 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. 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)]. 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.
ISSN:1386-6532
1873-5967
DOI:10.1016/j.jcv.2019.09.008