DNA methylation markers have universal prognostic value for anal cancer risk in HIV‐negative and HIV‐positive individuals. Issue 11 (16th March 2021)

• Record Type: Journal Article
• Authors: van der Zee, Ramon P.; van Noesel, Carel J.M.; Martin, Ivonne; ter Braak, Timo J.; Heideman, Daniëlle A.M.; de Vries, Henry J.C.; Prins, Jan M.; Steenbergen, Renske D.M.
• Is Part Of: Molecular oncology. Volume 15:Issue 11(2021)
• Page Start: 3024
• Page End: 3036
• Publication Date: 2021-03-16
• Subjects: anal cancer -- anal intraepithelial neoplasia -- host cell DNA methylation markers -- HIV -- human papillomavirus; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12926
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Anal cancer has increasing incidence and is preceded by high‐grade anal intraepithelial neoplasia (HGAIN; AIN2–3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV‐positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV‐negative risk groups. A cross‐sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV‐negative women and men was tested for six methylation markers ( ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582 ). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed‐effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease ( P < 0.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection [area under the curve (AUC): 0.83–0.86]. The optimal marker panel ( ASCL1 and ZIC1 ; AUC = 0.85 for AIN3+) detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV‐negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programmes. Abstract : Host cell DNA methylation plays a role in anal carcinogenesis in HIV‐negative (HIV‐neg) and HIV‐positive (HIV+) individuals, including men who have sex with men (MSM). Methylation levels are increased in high‐grade anal intraepithelial neoplasia at risk of progression towards anal cancer, making methylation markers promising prognostic biomarkers.