{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:03:40Z","timestamp":1790291020743,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    High\u2010risk human papillomavirus (hrHPV) infection is the primary cause of cervical cancer. However, hrHPV testing lacks specificity in detecting neoplastic changes. This study explored the utility of quantitative methylated HPV DNA markers for precise detection of cervical lesions. Using hybridization capture\u2010based bisulfite sequencing, we analyzed genome\u2010wide HPV methylation patterns. The study included a training cohort of 60 cervical exfoliated cell samples and a validation cohort of 29 samples. Analysis of 112 CpG sites across the HPV genome revealed that genome\u2010wide HPV16 methylation levels correlated with disease progression. Squamous cell carcinoma (SCC) showed 1.4\u2010fold higher methylation levels compared to normal tissue (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0032). Progressive methylation increases in the E5\u2010\u03b1 and L2 genes were observed across the spectrum of cervical lesion severity, from normal tissue through high\u2010grade squamous intraepithelial lesion (HSIL) to SCC. Intersection analysis of differentially methylated CpG sites between HSIL vs Normal and SCC vs Normal identified 16 consistently hypermethylated CpG sites in the E5\u2010\u03b1, E7, L2, and L1 genes, distinguishing both HSIL and SCC from normal tissue. This pilot study identifies a five\u2010CpG methylation panel (E5\u2010\u03b1_3887, E5\u2010\u03b1_3941, E7_701, L2_4441, and L2_5128) as promising triage biomarkers for HPV16\u2010positive women, achieving high discriminatory performance (AUC\u2009=\u20090.919 in a validation cohort) for detecting cervical lesions. This genome\u2010wide capture sequencing identified novel HPV16 methylation markers that distinguish cervical lesions from normal tissue, supporting the feasibility of HPV methylation\u2010based triage for HPV\u2010positive women in cervical cancer screening.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70739","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T13:07:11Z","timestamp":1765199231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High\u2010Throughput Targeted Sequencing Identifies an HPV Methylation Panel for Detecting Cervical Lesion Progression"],"prefix":"10.1002","volume":"97","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology, Xi'an People's Hospital (Xi'an Fourth Hospital) Affiliated People's Hospital Northwest University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gynecology Yue Bei People's Hospital Guangdong Shaoguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Health Management Center, the Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan University Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Academician expert workstation, the Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tian","sequence":"additional","affiliation":[{"name":"Generulor Co. 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