Clinical validation of the Cobas 4800 HPV assay using cervical samples in SurePath medium under the VALGENT4 framework

Background: The VALidation of HPV Genotyping Tests (VALGENT) framework is an international cooperation designed for comparison and clinical validation of HPV assays with genotyping capabilities. Objectives: Here we addressed the accuracy of the Roche cobas 4800 HPV test using SurePath samples from the Danish cervical cancer screening program under the VALGENT framework. Material and Methods: The VALGENT4 panel comprises 998 consecutive SurePath cervical samples from routine screening and 297 SurePath samples enriched for disease (100 ASC-US, 100 LSIL, 97 HSIL). The cobas HPV test is a real-time PCR assay which detects HPV16 and 18 individually and 12 other high-risk (hr) HPV genotypes in one bulk. Results: The clinical performance of the cobas test was assessed relative to that of the comparator assay GP5+/6 + PCR Enzyme ImmunoAssay (GP-EIA) by a non-inferiority test. The relative sensitivity for >= CIN2 was 1.00 (95% CI: 0.97-1.04) and relative specificity for the control group was 1.02 (95% CI: 1.01-1.04). The cobas test was found non-inferior to that of GP-EIA for both sensitivity and specificity (p-0.0006 and p< 0.0001, respectively). The type specific performance of the cobas test was evaluated using the GP5+/6 + PCR with Luminex genotyping (GP-LMNX) as comparator. The cobas test showed excellent to good concordance (Kappa: 0.70 to 0.90) with GP-LMNX for all three genotype groups in the overall VALGENT population but good to moderate concordance in the Screening population (kappa from 0.56 to 0.80). Conclusions: The cobas HPV test demonstrated non-inferiority to the comparator assay on cervical SurePath screening samples using the VALGENT4 panel.