title: Validation of a DNA methylation HPV triage classifier in a screening sample.
abstract: High-risk human papillomavirus (hrHPV) DNA tests have excellent sensitivity for detection of cervical intraepithelial neoplasia 2 or higher (CIN2+). A drawback of hrHPV screening, however, is modest specificity. Therefore, hrHPV-positive women might need triage to reduce adverse events and costs associated with unnecessary colposcopy. We compared the performance of HPV16/18 genotyping with a predefined DNA methylation triage test (S5) based on target regions of the human gene EPB41L3, and viral late gene regions of HPV16, HPV18, HPV31 and HPV33. Assays were run using exfoliated cervical specimens from 710 women attending routine screening, of whom 38 were diagnosed with CIN2+ within a year after triage to colposcopy based on cytology and 341 were hrHPV positive. Sensitivity and specificity of the investigated triage methods were compared by McNemar's test. At the predefined cutoff, S5 showed better sensitivity than HPV16/18 genotyping (74% vs 54%, P = 0.04) in identifying CIN2+ in hrHPV-positive women, and similar specificity (65% vs 71%, P = 0.07). When the S5 cutoff was altered to allow equal sensitivity to that of genotyping, a significantly higher specificity of 91% was reached (P < 0.0001). Thus, a DNA methylation test for the triage of hrHPV-positive women on original screening specimens might be a valid approach with better performance than genotyping.
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Attila T
authors.initials: AT
authors.lastname: Lorincz
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Brentnall
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Dorota
authors.initials: D
authors.lastname: Scibior-Bentkowska
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Reuter
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Rawinder
authors.initials: R
authors.lastname: Banwait
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Cadman
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Austin
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.affiliation: Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
authors.forename: Natasa
authors.initials: N
authors.lastname: Vasiljević
mesh_terms: D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D052161:Human papillomavirus 18 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D058952:Human papillomavirus 31 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics; D009367:Neoplasm Staging; D011247:Pregnancy; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics* / Q000821:virology
chemical_list: C116887:EPB41L3 protein, human; D008840:Microfilament Proteins
keywords: DNA methylation; HPV; biomarkers; cervical cancer; triage