title: Quality assurance of human papillomavirus (HPV) testing in the implementation of HPV primary screening in Norway: an inter-laboratory reproducibility study.
abstract: BACKGROUND
  Human papillomavirus (HPV) testing as primary screening for cervical cancer is currently being implemented in Norway in a randomized controlled fashion, involving three laboratories. As part of the quality assurance programme of the implementation, an evaluation of the inter-laboratory reproducibility of the HPV test was initiated, to ensure satisfactory HPV test reliability in all three laboratories.
  
  
  METHODS
  The HPV test used is the cobas 4800 HPV Test, detecting 14 high-risk types with individual HPV genotype results for HPV16 and HPV18. In addition to the three laboratories involved in the implementation, the Norwegian HPV reference laboratory was included as a fourth comparative laboratory. A stratified sample of 500 cervical liquid based cytology (LBC) samples was used in the evaluation, with an aim towards a high-risk HPV positivity of ~25%. Samples were collected at one laboratory, anonymized, aliquoted, and distributed to the other laboratories.
  
  
  RESULTS
  Comparison of the test results of all four laboratories revealed a 95.6% agreement, an 86.3% positive agreement and a kappa value of 0.94 (95% CI 0.92-0.97). For negative cytology specimens, there was a 95.8% overall agreement, a 67.4% positive agreement, and a kappa value of 0.88 (95% CI 0.80-0.93). For abnormal cytology specimens, there was a 95.8% overall agreement, a 95.5% positive agreement, and a kappa value of 0.86 (95% CI 0.71-0.97).
  
  
  CONCLUSIONS
  The study showed a high inter-laboratory reproducibility of HPV testing, implying satisfactory user performance and reliability in the laboratories involved in the implementation project. This is important knowledge and we recommend similar studies always to be performed prior to the introduction of new screening routines.
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Birgit
authors.initials: B
authors.lastname: Engesæter
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen Hidle
authors.affiliation: Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Mona
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Pia
authors.initials: P
authors.lastname: Moltu
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjersti Mangseth
authors.initials: KM
authors.lastname: Staby
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Siri
authors.initials: S
authors.lastname: Borchgrevink-Persen
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|The Gade Laboratory for Pathology, Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway.
authors.forename: Olav K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lönnberg
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Nygård
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.|Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway.
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.affiliation: Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway. irene.kraus.christiansen@ahus.no.
authors.forename: Irene Kraus
authors.initials: IK
authors.lastname: Christiansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D008403:Mass Screening / Q000592:standards*; D008875:Middle Aged; D009664:Norway; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D011785:Quality Assurance, Health Care; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D055815:Young Adult
keywords: Cervical cancer screening; Cobas 4800 HPV Test; HPV; HPV primary screening; HPV testing; Human papillomavirus; Inter-laboratory reproducibility; Quality assurance