{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:09:24Z","timestamp":1791220164419,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Medical Science and Technology Foundation of Zhejiang Province","award":["2020KY020"],"award-info":[{"award-number":["2020KY020"]}]},{"name":"Medical Science and Technology Foundation of Zhejiang Province","award":["2023KY013"],"award-info":[{"award-number":["2023KY013"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-01422-3","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:10:21Z","timestamp":1747818621000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The role of PAX1 and JAM3 methylation in predicting the pathological upgrading of cervical intraepithelial neoplasia before conization"],"prefix":"10.1038","volume":"15","author":[{"given":"Xiaoyan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafeng","family":"Shou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"issue":"3","key":"1422_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71(3), 209\u2013249 (2021).","journal-title":"CA Cancer J. Clin."},{"key":"1422_CR2","unstructured":"WHO Guideline for Screening and Treatment of Cervical pre-cancer Lesions for Cervical cancer Prevention (Geneva, 2021)."},{"issue":"1","key":"1422_CR3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/bjc.1989.236","volume":"60","author":"L Gustafsson","year":"1989","unstructured":"Gustafsson, L. & Adami, H. O. Natural history of cervical neoplasia: Consistent results obtained by an identification technique. Br. J. Cancer. 60(1), 132\u2013141 (1989).","journal-title":"Br. J. Cancer"},{"issue":"9430","key":"1422_CR4","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S0140-6736(04)16674-9","volume":"364","author":"J Peto","year":"2004","unstructured":"Peto, J. et al. The cervical cancer epidemic that screening has prevented in the UK. Lancet 364(9430), 249\u2013256 (2004).","journal-title":"Lancet"},{"key":"1422_CR5","doi-asserted-by":"publisher","first-page":"k499","DOI":"10.1136\/bmj.k499","volume":"360","author":"K Tainio","year":"2018","unstructured":"Tainio, K. et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ 360, k499 (2018).","journal-title":"BMJ"},{"issue":"4","key":"1422_CR6","doi-asserted-by":"publisher","first-page":"477","DOI":"10.5468\/ogs.2018.61.4.477","volume":"61","author":"Y Jung","year":"2018","unstructured":"Jung, Y. et al. Clinical factors that affect diagnostic discrepancy between colposcopically directed biopsies and loop electrosurgical excision procedure conization of the uterine cervix. Obstet. Gynecol. Sci. 61(4), 477\u2013488 (2018).","journal-title":"Obstet. Gynecol. Sci."},{"issue":"11","key":"1422_CR7","first-page":"CD012847","volume":"11","author":"M Kyrgiou","year":"2017","unstructured":"Kyrgiou, M. et al. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst. Rev. 11(11), CD012847 (2017).","journal-title":"Cochrane Database Syst. Rev."},{"key":"1422_CR8","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.semcdb.2015.08.014","volume":"44","author":"VR Paixao-Cortes","year":"2015","unstructured":"Paixao-Cortes, V. R., Salzano, F. M. & Bortolini, M. C. Origins and evolvability of the PAX family. Semin Cell. Dev. Biol. 44, 64\u201374 (2015).","journal-title":"Semin Cell. Dev. Biol."},{"key":"1422_CR9","doi-asserted-by":"crossref","unstructured":"Yamazaki, Y. et al. PAX1 is essential for development and function of the human thymus. Sci. Immunol.  5(44)  (2020).","DOI":"10.1126\/sciimmunol.aax1036"},{"issue":"1","key":"1422_CR10","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3892\/br.2021.1436","volume":"15","author":"MLR Da Silva","year":"2021","unstructured":"Da Silva, M. L. R. et al. The role of HPV-induced epigenetic changes in cervical carcinogenesis (review). Biomed. Rep. 15(1), 60 (2021).","journal-title":"Biomed. Rep."},{"issue":"1","key":"1422_CR11","doi-asserted-by":"publisher","first-page":"9195","DOI":"10.1038\/s41598-019-45477-5","volume":"9","author":"PH Su","year":"2019","unstructured":"Su, P. H. et al. Paired box-1 (PAX1) activates multiple phosphatases and inhibits kinase cascades in cervical cancer. Sci. Rep. 9(1), 9195 (2019).","journal-title":"Sci. Rep."},{"issue":"7","key":"1422_CR12","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1097\/IGC.0000000000001011","volume":"27","author":"T Luan","year":"2017","unstructured":"Luan, T. et al. PAX1 methylation as a potential biomarker to predict the progression of cervical intraepithelial neoplasia: A meta-analysis of related studies. Int. J. Gynecol. Cancer. 27(7), 1480\u20131488 (2017).","journal-title":"Int. J. Gynecol. Cancer"},{"issue":"3","key":"1422_CR13","doi-asserted-by":"publisher","first-page":"e506","DOI":"10.1002\/mgg3.506","volume":"7","author":"C Fang","year":"2019","unstructured":"Fang, C. et al. The promising role of PAX1 (aliases: HUP48, OFC2) gene methylation in cancer screening. Mol. Genet. Genomic Med. 7(3), e506 (2019).","journal-title":"Mol. Genet. Genomic Med."},{"key":"1422_CR14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13148-016-0196-3","volume":"8","author":"A Boers","year":"2016","unstructured":"Boers, A. et al. Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2\/3. Clin. Epigenet.  8, 29 (2016).","journal-title":"Clin. Epigenet."},{"issue":"1","key":"1422_CR15","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13148-020-00885-7","volume":"12","author":"L Kong","year":"2020","unstructured":"Kong, L. et al. DNA methylation for cervical cancer screening: A training set in China. Clin. Epigenetics 12(1), 91 (2020).","journal-title":"Clin. Epigenetics"},{"issue":"6","key":"1422_CR16","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/bjc.2014.392","volume":"111","author":"A Boers","year":"2014","unstructured":"Boers, A. et al. DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women. Br. J. Cancer. 111(6), 1095\u20131101 (2014).","journal-title":"Br. J. Cancer"},{"issue":"1","key":"1422_CR17","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/AOG.0b013e318254f90c","volume":"120","author":"J Bornstein","year":"2012","unstructured":"Bornstein, J. et al. 2011 Colposcopic terminology of the international federation for cervical pathology and colposcopy. Obstet. Gynecol. 120(1), 166\u2013172 (2012).","journal-title":"Obstet. Gynecol."},{"key":"1422_CR18","doi-asserted-by":"crossref","unstructured":"Urbano, A. et al. Gene-Specific targeting of DNA methylation in the mammalian genome. Cancers (Basel) 11(10)  (2019).","DOI":"10.3390\/cancers11101515"},{"issue":"3","key":"1422_CR19","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nrg3354","volume":"14","author":"ZD Smith","year":"2013","unstructured":"Smith, Z. D. & Meissner, A. DNA methylation: Roles in mammalian development. Nat. Rev. Genet. 14 (3), 204\u2013220 (2013).","journal-title":"Nat. Rev. Genet."},{"issue":"7","key":"1422_CR20","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41571-018-0004-4","volume":"15","author":"A Koch","year":"2018","unstructured":"Koch, A. et al. Analysis of DNA methylation in cancer: Location revisited. Nat. Rev. Clin. Oncol. 15(7), 459\u2013466 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"1422_CR21","unstructured":"https:\/\/www.nmpa.gov.cn\/"},{"key":"1422_CR22","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/978-1-61779-612-8_9","volume":"863","author":"Q Lu","year":"2012","unstructured":"Lu, Q., Ma, D. & Zhao, S. DNA methylation changes in cervical cancers. Methods Mol. Biol. 863, 155\u2013176 (2012).","journal-title":"Methods Mol. Biol."},{"issue":"26","key":"1422_CR23","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1200\/JCO.21.02433","volume":"40","author":"WW Kremer","year":"2022","unstructured":"Kremer, W. W. et al. Clinical regression of High-Grade cervical intraepithelial neoplasia is associated with absence of FAM19A4\/miR124-2 DNA methylation (CONCERVE Study). J. Clin. Oncol. 40(26), 3037\u20133046 (2022).","journal-title":"J. Clin. Oncol."},{"key":"1422_CR24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.3389\/fgene.2020.00347","volume":"11","author":"H Zhu","year":"2020","unstructured":"Zhu, H. et al. DNA methylation and hydroxymethylation in cervical cancer: Diagnosis, prognosis and treatment. Front. Genet. 11, 347 (2020).","journal-title":"Front. Genet."},{"issue":"2","key":"1422_CR25","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00281-019-00773-0","volume":"42","author":"M Burley","year":"2020","unstructured":"Burley, M., Roberts, S. & Parish, J. L. Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Semin Immunopathol. 42(2), 159\u2013171 (2020).","journal-title":"Semin Immunopathol."},{"issue":"2","key":"1422_CR26","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2217\/epi.09.33","volume":"1","author":"M Ehrlich","year":"2009","unstructured":"Ehrlich, M. DNA hypomethylation in cancer cells. Epigenomics 1(2), 239\u2013259 (2009).","journal-title":"Epigenomics"},{"key":"1422_CR27","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.mrrev.2016.09.006","volume":"772","author":"J Durzynska","year":"2017","unstructured":"Durzynska, J., Lesniewicz, K. & Poreba, E. Human papillomaviruses in epigenetic regulations. Mutat. Res. Rev. Mutat. Res. 772, 36\u201350 (2017).","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"issue":"6","key":"1422_CR28","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/nrc3728","volume":"14","author":"RD Steenbergen","year":"2014","unstructured":"Steenbergen, R. D. et al. Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat. Rev. Cancer 14(6), 395\u2013405 (2014).","journal-title":"Nat. Rev. Cancer"},{"issue":"4","key":"1422_CR29","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.3802\/jgo.2017.28.e56","volume":"28","author":"YW Hsu","year":"2017","unstructured":"Hsu, Y. W. et al. Genotype-specific methylation of HPV in cervical intraepithelial neoplasia. J. Gynecol. Oncol. 28 (4), e56 (2017).","journal-title":"J. Gynecol. Oncol."},{"issue":"3","key":"1422_CR30","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.semcancer.2009.02.011","volume":"19","author":"A Szalmas","year":"2009","unstructured":"Szalmas, A. & Konya, J. Epigenetic alterations in cervical carcinogenesis. Semin Cancer Biol. 19(3), 144\u2013152 (2009).","journal-title":"Semin Cancer Biol."},{"issue":"1","key":"1422_CR31","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1186\/s12885-021-08406-2","volume":"21","author":"J Zhao","year":"2021","unstructured":"Zhao, J. et al. SOX14 hypermethylation as a tumour biomarker in cervical cancer. BMC Cancer. 21(1), 675 (2021).","journal-title":"BMC Cancer"},{"issue":"1","key":"1422_CR32","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/ijc.23519","volume":"123","author":"HC Lai","year":"2008","unstructured":"Lai, H. C. et al. Identification of novel DNA methylation markers in cervical cancer. Int. J. Cancer. 123(1), 161\u2013167 (2008).","journal-title":"Int. J. Cancer"},{"issue":"2","key":"1422_CR33","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.ygyno.2021.02.011","volume":"161","author":"CL Chang","year":"2021","unstructured":"Chang, C. L. et al. DNA methylation marker for the triage of HrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan. Gynecol. Oncol. 161(2), 429\u2013435 (2021).","journal-title":"Gynecol. Oncol."},{"issue":"37","key":"1422_CR34","doi-asserted-by":"publisher","first-page":"62274","DOI":"10.18632\/oncotarget.19459","volume":"8","author":"Y Tian","year":"2017","unstructured":"Tian, Y. et al. Utility of gene methylation analysis, cytological examination, and HPV-16\/18 genotyping in triage of high-risk human papilloma virus-positive women. Oncotarget 8 (37), 62274\u201362285 (2017).","journal-title":"Oncotarget"},{"issue":"17","key":"1422_CR35","doi-asserted-by":"publisher","first-page":"5136","DOI":"10.7150\/jca.57460","volume":"12","author":"X Li","year":"2021","unstructured":"Li, X. et al. Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer. J. Cancer. 12(17), 5136\u20135143 (2021).","journal-title":"J. Cancer"},{"key":"1422_CR36","doi-asserted-by":"publisher","first-page":"3981529","DOI":"10.1155\/2020\/3981529","volume":"2020","author":"Z Zhao","year":"2020","unstructured":"Zhao, Z. et al. SOX1 and PAX1 are hypermethylated in cervical adenocarcinoma and associated with better prognosis. Biomed. Res. Int. 2020, 3981529 (2020).","journal-title":"Biomed. Res. Int."},{"key":"1422_CR37","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13148-016-0232-3","volume":"8","author":"YL Liou","year":"2016","unstructured":"Liou, Y. L. et al. Combined clinical and genetic testing algorithm for cervical cancer diagnosis. Clin. Epigenetics. 8, 66 (2016).","journal-title":"Clin. Epigenetics"},{"issue":"3","key":"1422_CR38","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/1471-0528.16395","volume":"128","author":"WW Kremer","year":"2021","unstructured":"Kremer, W. W. et al. The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: A review. BJOG 128(3), 504\u2013514 (2021).","journal-title":"BJOG"},{"key":"1422_CR39","doi-asserted-by":"publisher","first-page":"831949","DOI":"10.3389\/fonc.2022.831949","volume":"12","author":"L Zhang","year":"2022","unstructured":"Zhang, L. et al. Detection of host cell Gene\/HPV DNA methylation markers: A promising triage approach for cervical cancer. Front. Oncol. 12, 831949 (2022).","journal-title":"Front. Oncol."},{"issue":"5","key":"1422_CR40","doi-asserted-by":"publisher","first-page":"ofac013","DOI":"10.1093\/ofid\/ofac013","volume":"9","author":"K Fu","year":"2022","unstructured":"Fu, K. et al. Triage by PAX1 and ZNF582 methylation in women with cervical intraepithelial neoplasia grade 3: A multicenter case-control study. Open. Forum Infect. Dis. 9(5), ofac013 (2022).","journal-title":"Open. Forum Infect. Dis."},{"key":"1422_CR41","unstructured":"Xiao, S. et al. Multicenter study on PAX1\/JAM3 dual gene methylation detection in cervical cytology for cervical cancer screening. Chin. Med. J. 104(20), 1852\u20131859 (2024)"},{"key":"1422_CR42","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s13148-024-01804-w","volume":"16","author":"J Fei","year":"2024","unstructured":"Fei, J. et al. Evaluating PAX1\/JAM3 methylation for triage in HPV 16\/18-infected women. Clin. Epigenet. 16, 190 (2024).","journal-title":"Clin. Epigenet."},{"key":"1422_CR43","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1186\/s12885-024-13082-z","volume":"24","author":"X Chen","year":"2024","unstructured":"Chen, X. et al. Cervical cancer screening: Efficacy of PAX1 and JAM3 methylation assay in the triage of atypical squamous cell of undetermined significance (ASC-US). BMC Cancer 24, 1385 (2024).","journal-title":"BMC Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01422-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01422-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01422-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:10:24Z","timestamp":1747818624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-01422-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1422"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-01422-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5985038\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"8 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17684"}}