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DNA methylation analysis on anal swabs for anal cancer screening in people living with HIV. | LitMetric

AI Article Synopsis

Article Abstract

Introduction: High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, we showed that DNA methylation analysis of anal high-grade squamous intraepithelial lesions (HSIL) biopsies can distinguish between HSIL with an increased cancer risk, and HSIL with a low cancer risk, in which treatment may be safely withheld. Here, we assessed the performance of methylation analysis in anal swabs to identify patients with underlying HSIL with an increased cancer risk.

Methods: A cross-sectional series of paired anal swabs and biopsies of 215 persons with HIV and swabs of 19 anal cancer patients were tested for 6 methylation markers. Data were analysed by logistic regression analysis. The primary endpoint was methylation-positive biopsy HSIL (M+HSIL), indicating increased cancer risk. Test performance on swabs of methylation markers, HPV and/or cytology, as well as cancer detection and HRA referral rates were calculated.

Results: Anal cancer swabs had the highest methylation levels. ZNF582, and marker panels ASCL1/ZNF582 and LHX8/ZNF582 yielded an area-under-the-curve of 0.68 to 0.70 to detect underlying M+HSIL. LHX8/ZNF582 methylation at 80% sensitivity corresponded to 43% fewer patients requiring HRA, without missing any anal cancers and detecting 79% of HPV16-positive HSIL-anal intraepithelial neoplasia grade 3. Methylation and HPV co-testing performed similarly to cytology and HPV co-testing.

Conclusion: DNA methylation levels in anal swabs reflect underlying anal disease. Methylation analysis could reduce HRA referrals substantially, while maintaining a high sensitivity for M+HSIL and detecting all cancers. These results encourage screening on anal swabs to preselect patients that require HRA.

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Source
http://dx.doi.org/10.1093/infdis/jiae627DOI Listing

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