Lorincz, Attila T;
Nathan, Mayura;
Reuter, Caroline;
Warman, Rhian;
Thaha, Mohamed A;
Sheaff, Michael;
Vasiljevic, Natasa;
... Sasieni, Peter; + view all
(2017)
Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions.
Oncotarget
, 8
(31)
pp. 50510-50520.
10.18632/oncotarget.17984.
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Abstract
We studied DNA methylation patterns of human papillomavirus (HPV) and tumor suppressor gene EPB41L3 in 148 anal and perianal biopsies to determine whether high levels of methylation would be associated with anal intraepithelial neoplasia (AIN). The most prevalent HPV type was HPV16, detected in 54% of the 30 benign biopsies, 33% of the 43 low-grade AIN (lgAIN), 82% of the 59 high grade AIN (hgAIN) and 4 of the 5 anal cancers. A methylation score was developed (0.561*HPV16me+0.439*EPB41L3) which had increasing values with severity of disease: the mean was 8.1% in benign, 13.2% in lgAIN, 22.3% in hgAIN and 49.3% in cancers (p < 0.0001). The methylation score as a triage classifier at a cut-off of 8.8 gave a sensitivity of 90.6% (95% CI: 82.8, 96.9), specificity of 50.7% (95% CI: 39.7, 61.6) and area under the curve of 0.82 (95% CI: 0.75–0.89) for separating hgAIN and cancer from benign and lgAIN biopsies. We conclude that methylation of HPV16 and EPB41L3 show highly significant association with increasing severity of AIN and cancer and may be useful as biomarkers in anal disease.
| Type: | Article |
|---|---|
| Title: | Methylation of HPV and a tumor suppressor gene reveals anal cancer and precursor lesions |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.17984 |
| Publisher version: | https://doi.org/10.18632/oncotarget.17984 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Anal cancer, intraepithelial neoplasia, DNA methylation, high-risk human papillomavirus, HPV genotyping |
| 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/10179414 |
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