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Classification systems based on p16 and Ki67 expression cumulative scores (0\u20133 each)\u2014p16\/Ki67 collectively known as an immunoscore [IS]\u2014are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16\/Ki-67 IS, and <jats:italic>PAX1<\/jats:italic>\/<jats:italic>ZNF582<\/jats:italic> methylation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this study, 414 HPV-positive paraffin-embedded specimens were collected, and <jats:italic>PAX1<\/jats:italic>\/<jats:italic>ZNF582<\/jats:italic> methylation and the p16\/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between <jats:italic>PAX1<\/jats:italic>\/<jats:italic>ZNF582<\/jats:italic> methylation and p16\/Ki6 immunohistochemical staining scores was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The \u0394Cp of <jats:italic>PAX1<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup> (<jats:italic>PAX1<\/jats:italic> methylation) and <jats:italic>ZNF582<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup> (<jats:italic>ZNF582<\/jats:italic> methylation) decreased with cervical lesion severity (Cuzick trend test, all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The severity of the cervical lesions and p16, Ki67, and p16\/Ki67 IS showed an increasing trend (Multinomial Cochran-Armitage trend test, all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The prevalence of <jats:italic>PAX1<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>\/<jats:italic>ZNF582<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup> increased with an increase in the IS of p16, Ki67, and p16\/Ki67 (Cochran-Armitage trend test, all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In cervical SCC, the IS was 5\u20136, and the <jats:italic>PAX1<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>\/<jats:italic>ZNF582<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup> was positive. Meanwhile, heterogeneity was observed in CIN lesions: 10 cases had an IS of 3\u20134 and were <jats:italic>PAX1<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>\/<jats:italic>ZNF582<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>-positive in \u2264\u2009CIN1; 1 case had an IS of 0\u20132 and was <jats:italic>PAX1<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>\/<jats:italic>ZNF582<\/jats:italic><jats:sup><jats:italic>m<\/jats:italic><\/jats:sup>-positive in CIN2\/3.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Significant heterogeneity was observed in CIN lesions for p16 and Ki67 immunohistochemical staining scores and <jats:italic>PAX1<\/jats:italic>\/<jats:italic>ZNF582<\/jats:italic> methylation. This may help clinicians personalize the management of CIN based on the predicted short-term risk of cancer progression, minimizing the rate of missed CIN1 diagnoses and incorrect treatment of CIN2\/3.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-024-12920-4","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T07:02:04Z","timestamp":1726815724000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Relationship between p16\/ki67 immunoscores and PAX1\/ZNF582 methylation status in precancerous and cancerous cervical lesions in high-risk HPV-positive women"],"prefix":"10.1186","volume":"24","author":[{"given":"Haijun","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shali","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"12920_CR1","first-page":"384","volume":"55","author":"SD Balasubramaniam","year":"2019","unstructured":"Balasubramaniam SD, Balakrishnan V, Oon CE, Kaur G. 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Molecular progression to cervical precancer, epigenetic switch or sequential model? 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Informed consent was obtained from all patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1171"}}