Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus–Positive Men by Validated Methylation Markers Associated With Progression to Cancer

• Published in: Clinical infectious diseases 2021-06, Vol.72 (12), p.2154-2163
• Main Authors: van der Zee, Ramon P, Richel, Olivier, van Noesel, Carel J M, Ciocănea-Teodorescu, Iuliana, van Splunter, Annina P, ter Braak, Timo J, Nathan, Mayura, Cuming, Tamzin, Sheaff, Michael, Kreuter, Alexander, Meijer, Chris J L M, Quint, Wim G V, de Vries, Henry J C, Prins, Jan M, Steenbergen, Renske D M
• Format: Article
• Language: English
• Subjects: Major and Commentaries
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciaa397

Abstract Background High-grade anal intraepithelial neoplasia (HGAIN; AIN2–3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. Methods A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. Results Methylation levels of all genes increased with increasing severity of disease (P