title: Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests).
abstract: The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening.
authors.affiliation: Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom kate.cuschieri@luht.scot.nhs.uk.
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: Geraets
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Cadman
authors.affiliation: Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Moore
authors.affiliation: National Reference Centre for HPV, Brussels, Belgium International Centre for Reproductive Health, Ghent University, Ghent, Belgium Laboratory of Molecular Pathology, AML, Antwerp, Belgium.
authors.forename: Davy
authors.initials: D
authors.lastname: Vanden Broeck
authors.affiliation: National Reference Centre for HPV, Brussels, Belgium Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium School of Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Padalko
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.affiliation: Unit of Cancer Epidemiology and Belgian Cancer Centre, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D006113:United Kingdom; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D055815:Young Adult