{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:46:46Z","timestamp":1787928406320,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI027757"],"award-info":[{"award-number":["P30AI027757"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2024,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high\u2010grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low\u2010grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged \u226518\u2009years undergoing high\u2010resolution anoscopy (HRA) in Seattle, Washington, 2015\u20132016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0\u2009years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01\u20131.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08\u20131.20) methylation were significantly associated with HSIL versus NILM\/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01\u20131.11) and FMN2 (aOR: 1.13, 95% CI: 1.08\u20131.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.<\/jats:p>","DOI":"10.1002\/ijc.34977","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T07:39:52Z","timestamp":1714376392000},"page":"1091-1100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Methylation markers for anal cancer screening: A repeated cross\u2010sectional analysis of people living with <scp>HIV<\/scp>, 2015\u20132016"],"prefix":"10.1002","volume":"155","author":[{"given":"Anjali","family":"Vasavada","sequence":"first","affiliation":[{"name":"Department of Epidemiology University of Washington School of Public Health  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Stankiewicz Karita","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases University of Washington School of Medicine  Seattle 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E.","family":"Hawes","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Washington School of Public Health  Seattle Washington USA"},{"name":"Department of Global Health University of Washington School of Public Health  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruanne V.","family":"Barnabas","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Wasserheit","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Washington School of Public Health  Seattle Washington USA"},{"name":"Division of Allergy and Infectious Diseases University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Medicine University of Washington School of Medicine  Seattle 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