{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:08:04Z","timestamp":1792469284799,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["D43TW009575"],"award-info":[{"award-number":["D43TW009575"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54CA221205"],"award-info":[{"award-number":["U54CA221205"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, with particularly high burdens among people living with HIV (PLWH) in low\u2010resource settings like Nigeria. Effective early detection remains a major challenge due to limited access to imaging\u2010based surveillance and the low sensitivity of current biomarkers such as alpha\u2010fetoprotein (AFP). We conducted an epigenome\u2010wide association study (EWAS) of circulating cell\u2010free DNA (ccfDNA) methylation in a Nigerian cohort of HIV\u2010positive individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009245), spanning HCC, cirrhosis (FibroScan \u226512.3\u2009kPa), fibrosis (FibroScan \u22657.6 and &lt;12.3\u2009kPa), and HCC\u2010free without fibrosis (FibroScan &lt;7.6\u2009kPa) groups. Using random forest modeling, we developed and evaluated a ccfDNA methylation classifier (ccfDNAmRF) for HCC risk prediction. We identified 73 CpG sites significantly associated with HCC (false discovery rate &lt;0.01). The ccfDNAmRF model demonstrated strong discriminatory power, achieving 100% sensitivity and 80%\u201391% specificity for distinguishing HCC from cirrhosis, fibrosis, and HCC\u2010free groups (area under the curve [AUC]: 92%\u201397%). Combining ccfDNA methylation risk scores with AFP further improved classification accuracy (AUC up to 98.5%). Notably, ccfDNA methylation patterns displayed clear dose\u2013response relationships across the disease spectrum, supporting their utility for early\u2010stage detection and risk stratification. Our findings highlight the promise of ccfDNA methylation biomarkers as a non\u2010invasive, blood\u2010based screening tool for improving early identification of HCC cases among PLWH.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70204","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:49:54Z","timestamp":1761238194000},"page":"1281-1291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating cell\u2010free\n                    <scp>DNA<\/scp>\n                    methylation biomarkers for hepatocellular carcinoma risk prediction in\n                    <scp>HIV<\/scp>\n                    \u2010positive Nigerian population"],"prefix":"10.1002","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-7320","authenticated-orcid":false,"given":"Yinan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhe","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishu","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Okeke","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantong M.","family":"Davwar","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J.","family":"Duguru","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nyam","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emuobor","family":"Odeghe","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganiyat","family":"Oyeleke","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunmilayo A.","family":"Lesi","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin E.","family":"Imade","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanmu A.","family":"Sulaimon","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimah B.","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kabir","family":"Badmos","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demirkan B.","family":"Gursel","sequence":"additional","affiliation":[{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Department of Pathology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olugbenga A.","family":"Silas","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masha","family":"Kocherginsky","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang\u2010Youn A.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zequn","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad J.","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Robert J. Havey MD Institute for Global Health Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Nursing Yale University  West Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-1731","authenticated-orcid":false,"given":"Hushan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atiene S.","family":"Sagay","sequence":"additional","affiliation":[{"name":"College of Health Sciences University of Jos  Jos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folasade T.","family":"Ogunsola","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Robert J. 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