title: Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays.
abstract: Laboratories now can choose from >100 human papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART, and Aptima, frequently do not detect the same HPV infections. Here, we determined the characteristics of the concordant samples (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30 to 65 years of age (n = 2,859) and in a concurrent referral population from the same catchment area (n = 885). HPV testing followed the manufacturers' protocols. Women with abnormal cytology were managed according to the routine recommendations. Cytology-normal/HPV-positive women were invited for repeated testing in 18 months. Screening history and histologically confirmed cervical intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women with discordant samples. Additionally, assay signal strengths were substantially higher in concordant samples. More than 80% of ≥CIN2 results were found for women with concordant samples, and no ≥CIN2 results were found when the infection was detected by only one assay. These patterns were similar in the referral population despite the younger age and higher number of HPV infections. HPV test result discordance identified a cluster of low-risk HPV infections that were hardly ever associated with high-grade CIN and, almost exclusively, represented false-positive screening findings.
authors.affiliation: Department of Public Health, University of Copenhagen, Copenhagen, Denmark m.rebolj@qmul.ac.uk.
authors.forename: Matejka
authors.identifier: 0000-0001-9597-645X
authors.initials: M
authors.lastname: Rebolj
authors.affiliation: Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Department of Pathology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Bonde
authors.affiliation: Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Department of Pathology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Sarah
authors.initials: S
authors.lastname: Preisler
authors.affiliation: Department of Pathology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Ejegod
authors.affiliation: Department of Pathology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rygaard
authors.affiliation: Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Elsebeth
authors.initials: E
authors.lastname: Lynge
mesh_terms: D000328:Adult; D000368:Aged; D003718:Denmark; D055088:Early Detection of Cancer; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology*