Lorincz, Attila T;
Brentnall, Adam R;
Scibior‐Bentkowska, Dorota;
Reuter, Caroline;
Banwait, Rawinder;
Cadman, Louise;
Austin, Janet;
... Vasiljević, Natasa; + view all
(2016)
Validation of a DNA methylation HPV triage classifier in a screening sample.
International Journal of Cancer
, 138
(11)
pp. 2745-2751.
10.1002/ijc.30008.
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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.
| Type: | Article |
|---|---|
| Title: | Validation of a DNA methylation HPV triage classifier in a screening sample |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ijc.30008 |
| Publisher version: | https://doi.org/10.1002/ijc.30008 |
| Language: | English |
| Additional information: | © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | HPV, DNA methylation, cervical cancer, triage, biomarkers |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10179418 |
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