Validation of EUROArray HPV test using the VALGENT framework.

ABSTRACT

BACKGROUND: Robust clinical and analytical validation of human papillomavirus (HPV) tests is a pre-requisite for their use in cervical cancer screening given the transience of most high-risk HPV infections. OBJECTIVES: To evaluate the EUROArray HPV test (PCR-based full HPV genotyping test) using the international validation of the VALGENT framework, which offers an opportunity to determine analytical and clinical performance according to internationally accepted performance metrics. STUDY DESIGN: A total of 1300 consecutive and 300 abnormal cervical samples derived from the Slovenian screening programme were tested with the EUROArray HPV test. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was performed and compared to a standard comparator test (Hybrid Capture 2). Intra- and inter-laboratory reproducibility of the assay was performed in a subset of 500 samples. RESULTS: The relative clinical sensitivity and specificity of EUROArray HPV vs HC2 was 0.93 (95% Confidence Interval (CI), 0.88-0.99; P non-inferiority(ni) = 0.1413) and 1.01 (95% CI, 0.99-1.02; Pni = 0.0001), respectively. Application of an a-posteriori cut-off for HPV16 led to relative values of 0.98 (95% CI, 0.92-1.03; Pni = 0.0076) and 1.00 (95% CI, 0.97-1.03; Pni = 0.007), respectively. The assay showed excellent intra- and inter-laboratory reproducibility (concordance ≥ 94%, Kappas ≥0.85). CONCLUSION: At the predefined cut-off, EUROArray HPV was less sensitive than HC2 for the detection of CIN2+. However, when an optimised cut-off was applied, EUROArray HPV fulfilled international criteria for its use in cervical cancer screening.