University of Groningen Comparing the Cervista HPV HR Test and Hybrid Capture 2 Assay in a Dutch Screening Population

The diagnostic performance of the widely-used Cervista HPV HR test was compared to the Hybrid Capture 2 (HC2) test in a Dutch population-based cervical cancer screening program. In 900 scrapings of women with normal cytomorphology, specificity was 90% (95%CI: 87.84–91.87) for the Cervista HPV HR test and 96% (95%CI: 94.76–97.37) for the HC2 test with 93% agreement between both tests (k= 0.5, p,0.001). The sensitivity for CIN2+ using 65 scrapings of women with histological-confirmed CIN2+ was 91% (95%CI: 80.97–96.51) for the Cervista HPV HR test and 92% (95%CI: 82.94–97.43) for the HC2 test with 95% agreement between both tests (k= 0.7, p,0.001). Fifty-seven of 60 HC2 negative/Cervista positive cases tested HPV-negative with PCR-based HPV assays; of these cases 56% were defined as Cervista triple-positive with FOZ values in all 3 mixes higher than the second cut-off of 1.93 (as set by manufacturer). By setting this cut-off at 5.0, specificity improved significantly without affecting sensitivity. External validation of this new cut-off at 5.0 in triple-positive scrapings of women selected from the SHENCCASTII database revealed that 22/24 histological normal cases now tested HPV-negative in the Cervista HPV HR test, while CIN2+ lesions remained HPV-positive. The intra-laboratory reproducibility of the Cervista HPV HR test (n = 510) showed a concordance of 92% and 93% for cut-off 1.93 and 5.0 (k= 0.83 and k= 0.84, p,0.001) and inter-laboratory agreement of the Cervista HPV HR test was 90% and 93% for cut-off 1.93 and 5.0 (k= 0.80 and k= 0.85, p, 0.001). In conclusion, the specificity of the Cervista HPV HR test could be improved significantly by increasing the second cut-off from 1.93 to 5.0, without affecting the sensitivity of the test in a population-based screening setting. Citation: Boers A, Slagter-Menkema L, van Hemel BM, Belinson JL, Ruitenbeek T, et al. (2014) Comparing the Cervista HPV HR Test and Hybrid Capture 2 Assay in a Dutch Screening Population: Improved Specificity of the Cervista HPV HR Test by Changing the Cut-Off. PLoS ONE 9(7): e101930. doi:10.1371/journal.pone. 0101930 Editor: Fausto Baldanti, Fondazione IRCCS Policlinico San Matteo, Italy Received January 8, 2014; Accepted June 13, 2014; Published July 22, 2014 Copyright: 2014 Boers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: AB is supported by the Dutch Cancer Society (RUG-NKB2009-4577). The Cervista HPV HR test reagents were kindly provided by Hologic Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have read the journal’s policy and have the following conflicts: Ed Scuuring is a member of the scientific advisory board of Roche, Hologic and QCMD, received travel reimbursements from Roche, Abbott, Hologic Inc. and QCMD. AB, LSM, BvH received travel reimbursements from Hologic Inc. Jerome L. Belinson has received support in kind (reagents and testing) and funds for direct support and research, under the auspices of Preventive Oncology International Inc., from Hologic Inc., Qiagen, Gen-Probe, Merck Inc., BGI Shenzen, and GE Healthcare. The Cervista HPV HR test reagents were kindly provided by Hologic Inc. for this study. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. * Email: e.schuuring@umcg.nl