{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:27:57Z","timestamp":1791959277997,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:p>Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin\u2010fixed, paraffin\u2010embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead\u2010based microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in individual CpG sites were compared using a <jats:italic>t<\/jats:italic>\u2010test, and results were summarized by computing <jats:italic>p<\/jats:italic>\u2010values. A total of 12 candidate genes (<jats:italic>ADCYAP1, ASCL1, ATP10, CADM1, DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17<\/jats:italic> and <jats:italic>TMEFF2)<\/jats:italic> identified by DNA methylation profiling, plus an additional three genes identified from the literature (<jats:italic>EPB41L3, MAL<\/jats:italic> and <jats:italic>miR\u2010124)<\/jats:italic> were chosen for validation in an independent set of 167 liquid\u2010based cytology specimens using pyrosequencing and targeted, next\u2010generation bisulfite sequencing. Of the 15 candidate gene markers, 10 had an area under the curve (AUC) of\u2009\u2265\u20090.75 for discrimination of high grade squamous intraepithelial lesions or worse (HSIL+) from &lt;HSIL cytology using at least one assay. Overall, <jats:italic>SOX1<\/jats:italic>, <jats:italic>DCC,<\/jats:italic> and <jats:italic>EPB41L3<\/jats:italic> showed the best discrimination with AUC values of \u22650.80, irrespective of methylation detection assay. In addition to verifying candidate markers from the literature (<jats:italic>e.g<\/jats:italic>., <jats:italic>SOX1<\/jats:italic> and <jats:italic>EPB41L3<\/jats:italic>), we identified novel markers that may be considered for detection of cervical precancer and cancer and warrant further validation in prospective studies.<\/jats:p>","DOI":"10.1002\/ijc.30781","type":"journal-article","created":{"date-parts":[[2017,5,13]],"date-time":"2017-05-13T08:42:21Z","timestamp":1494664941000},"page":"701-710","source":"Crossref","is-referenced-by-count":69,"title":["Discovery and validation of candidate host DNA methylation markers for detection of cervical precancer and cancer"],"prefix":"10.1002","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-7376","authenticated-orcid":false,"given":"Megan A.","family":"Clarke","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Luhn","sequence":"additional","affiliation":[{"name":"Genentech Inc South San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Gage","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Bodelon","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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