title: Interlaboratory reproducibility and proficiency testing within the human papillomavirus cervical cancer screening program in Catalonia, Spain.
abstract: In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.
authors.affiliation: Infections and Cancer Unit, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ibáñez
authors.forename: M
authors.initials: M
authors.lastname: Félez-Sánchez
authors.forename: J M
authors.initials: JM
authors.lastname: Godínez
authors.forename: C
authors.initials: C
authors.lastname: Guardià
authors.forename: E
authors.initials: E
authors.lastname: Caballero
authors.forename: R
authors.initials: R
authors.lastname: Juve
authors.forename: N
authors.initials: N
authors.lastname: Combalia
authors.forename: B
authors.initials: B
authors.lastname: Bellosillo
authors.forename: D
authors.initials: D
authors.lastname: Cuevas
authors.forename: J
authors.initials: J
authors.lastname: Moreno-Crespi
authors.forename: L
authors.initials: L
authors.lastname: Pons
authors.forename: J
authors.initials: J
authors.lastname: Autonell
authors.forename: C
authors.initials: C
authors.lastname: Gutierrez
authors.forename: J
authors.initials: J
authors.lastname: Ordi
authors.forename: S
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: I G
authors.initials: IG
authors.lastname: Bravo
mesh_terms: D004279:DNA, Viral / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D061809:Human Papillomavirus DNA Tests / Q000379:methods; D006801:Humans; D059021:Laboratory Proficiency Testing / Q000379:methods; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013030:Spain; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods
chemical_list: D004279:DNA, Viral