In:
Molecular Oncology, Wiley, Vol. 15, No. 11 ( 2021-11), p. 3024-3036
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.
Type of Medium:
Online Resource
ISSN:
1574-7891
,
1878-0261
DOI:
10.1002/1878-0261.12926
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2415106-3
detail.hit.zdb_id:
2322586-5