title: 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.
abstract: 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 (κ = 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 (κ = 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 (κ = 0.83 and κ = 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 (κ = 0.80 and κ = 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.
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Aniek
authors: A
authors: Boers
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Lorian
authors: L
authors: Slagter-Menkema
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Bettien M
authors: BM
authors: van Hemel
authors: Preventive Oncology International, Inc, Cleveland Heights and Lerner College of Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Jerome L
authors: JL
authors: Belinson
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Teus
authors: T
authors: Ruitenbeek
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Henk J
authors: HJ
authors: Buikema
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Harry
authors: H
authors: Klip
authors: Department of Pathology, AZ St Jan Brugge-Oostende, Brugge, Belgium.
authors: Hilde
authors: H
authors: Ghyssaert
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Ate G J
authors: AG
authors: van der Zee
authors: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Geertruida H
authors: GH
authors: de Bock
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: G Bea A
authors: GB
authors: Wisman
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Ed
authors: E
authors: Schuuring
mesh_terms: D000328:Adult; D055088:Early Detection of Cancer / Q000592:standards*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009426:Netherlands; D030361:Papillomavirus Infections / Q000175:diagnosis*; D058996:Quality Improvement; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000517:prevention & control