Open AccessDNA methylation markers have universal prognostic value for anal cancer risk in HIV‐negative and HIV‐positive individuals
Author(s) -
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.
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12926
Subject(s) - anal cancer , dna methylation , methylation , oncology , medicine , cancer , men who have sex with men , incidence (geometry) , human immunodeficiency virus (hiv) , biology , immunology , genetics , dna , gene , gene expression , physics , syphilis , optics
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.