title: VALGENT: A protocol for clinical validation of human papillomavirus assays.
abstract: BACKGROUND
  Testing for high-risk HPV is more effective in primary cervical cancer screening than the cytological examination of a Pap smear. Separate genotyping may be useful for triage in both HPV-based and cytology-based screening. Only clinically validated tests should be used in clinical practice.
  
  
  OBJECTIVE
  VALGENT is a study framework for test comparison and validation of HPV assays in general and HPV genotyping tests in particular according to clinically relevant outcomes and for clinical applications endorsed by scientific evidence.
  
  
  METHODS
  VALGENT involves the collation of fresh or archived cervical cell specimen from women attending routine screening supplemented with cytologically abnormal samples. Multiple aliquots of residual material are sent from a central laboratory to participating laboratories for testing with novel HPV assays with limited, extended or full genotyping capacity. Outcomes are derived from screening and pathology registries. Each VALGENT panel includes an assay already validated for screening. A series of accuracy and concordance statistics were generated.
  
  
  RESULTS
  Currently, two VALGENT study rounds, originated from laboratories in Antwerp (Belgium) and Edinburgh (Scotland), were completed. Two new assays (G5+/6+ PCR-LMNX and Xpert HPV) were validated for screening by showing similar accuracy for cervical precancer as the standard comparator test. For two other tests (BD Onclarity, PapilloCheck) validation was confirmed. Inter-test agreement was high although certain type-specific discordances were observed which warrant further analysis.
  
  
  CONCLUSIONS
  VALGENT extends current guidelines for high-risk HPV test validation in cervical cancer screening and has produced a large study resource for test comparison. More robust procedures of sample selection and handling and integration with the global WHO reference laboratory network focusing on analytical accuracy, may result in the generation of an international standard and a formalized system for clinical validation of HPV assays and quality control in HPV-based screening.
authors.affiliation: Unit of Cancer Epidemiology & Belgian Cancer Centre, Scientific Institute of Public Health, J. Wytsmanstreet 14, B1050 Brussels, Belgium. Electronic address: marc.arbyn@wiv-isp.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.affiliation: Department of Molecular Pathology, AML Laboratory, Sonic Healthcare, Antwerp, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Depuydt
authors.affiliation: Department of Molecular Pathology, AML Laboratory, Sonic Healthcare, Antwerp, Belgium.
authors.forename: Ina
authors.initials: I
authors.lastname: Benoy
authors.affiliation: Department of Molecular Pathology, AML Laboratory, Sonic Healthcare, Antwerp, Belgium.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bogers
authors.affiliation: Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.affiliation: Division Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Division Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: Geraets
authors.affiliation: French HPV Reference Laboratory, Institut Pasteur, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Heard
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mario
authors.initials: M
authors.lastname: Poljak
authors.affiliation: Department of Pathology and Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Bonde
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
mesh_terms: D000328:Adult; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D060005:Genotyping Techniques; D061809:Human Papillomavirus DNA Tests / Q000592:standards*; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D011933:Reagent Kits, Diagnostic / Q000592:standards* / Q000600:supply & distribution; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears; D054928:Validation Studies as Topic; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000175:diagnosis* / Q000821:virology
chemical_list: D011933:Reagent Kits, Diagnostic
keywords: Cervical cancer; Cervical cancer screening; Diagnostic test accuracy; Human papillomavirus; Quality control; Test validation