Comparison of analytical and clinical performance of CLART HPV2 genotyping assay to Linear Array and Hybrid Capture 2: a split-sample study

Background: Human Papillomavirus (HPV) genotyping has an increasingly important role in cervical cancer screening and vaccination monitoring, however, without an internationally agreed standard reference assay. The test results from the most widely used genotyping assays are read manually and hence prone to inter-observer variability. The reading of test results on the CLART HPV2 genotyping assay is, on the other hand, automated. The aim of our study was to directly compare the detection of HPV genotypes and high-grade cervical intraepithelial neoplasia (CIN) by CLART, Linear Array (LA), and Hybrid Capture 2 (HC2) using samples stored in SurePath. Methods: Residual material from 401 routine samples from women with abnormal cytology was tested by CLART, LA, and HC2 (ClinicalTrial.gov: NCT01671462, Ethical Committee approval: H-2012-070). Histological outcomes were ascertained by linkage to the Danish nation-wide Pathology Data Bank. For comparison of CLART and LA in terms of genotype detection, we calculated.-coefficients, and proportions of overall and positive agreement. For comparison of CIN detection between CLART, LA, and HC2, we calculated the relative sensitivity and specificity for high-grade CIN. Results: The kappa-coefficient for agreement in detection of genotypes 16, 18, 31, 33, 35, and 51 was >= 0.90 (overall agreement: 98-99%, positive agreement: 84-95%). The values were slightly lower, but still in the substantial range for genotypes 39, 45, 52, 56, 58, 59, and several low-risk genotypes. The relative sensitivity of CLART for >= CIN2 and >= CIN3 was not significantly lower than that of LA and HC2, although CLART showed a higher specificity than HC2. Conclusions: In Danish women with abnormal SurePath cytology, CLART and LA were highly comparable for detection of most high-risk and low-risk genotypes; and CLART's sensitivity for high-grade CIN was comparable to that of both LA and HC2.