Vasiljević, Nataša;
Carter, Paul D;
Reuter, Caroline;
Warman, Rhian;
Brentnall, Adam R;
Carton, James R;
Cuzick, Jack;
(2017)
Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia.
International Journal of Cancer
, 141
(4)
pp. 829-836.
10.1002/ijc.30783.
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Abstract
Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter‐reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (i) p16‐mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high‐risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT‐qPCR (p16‐mRNA assay) was run on mRNA extracted from formalin‐fixed paraffin‐embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high‐resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61–77) for 85% (95%CI 77–91%) sensitivity. The four‐point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71–0.82), compared with 0.71 (95%CI 0.64–0.77) for p16‐mRNA and 0.67 (95%CI 0.60–0.74) for Digital IHC. Spearman rank‐order correlations were: visual to p16‐mRNA 0.41, visual to digital 0.49 and p16‐mRNA to digital: 0.22. The addition of p16‐mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16‐mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists.
| Type: | Article |
|---|---|
| Title: | Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ijc.30783 |
| Publisher version: | https://doi.org/10.1002/ijc.30783 |
| Language: | English |
| Additional information: | © 2017 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. |
| 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/10179415 |
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