{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:27:56Z","timestamp":1791959276170,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T00:00:00Z","timestamp":1299801600000},"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":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Given the lower specificity for high\u2010grade cervical lesions of high\u2010risk human papillomavirus (hrHPV) testing compared to cytology, additional triage testing for hrHPV test\u2010positive women is needed to detect high\u2010grade cervical lesions. Here, we tested whether combined methylation analysis for cell adhesion molecule 1 (CADM1) and T\u2010lymphocyte maturation associated protein (MAL), both functionally involved in cervical carcinogenesis, could serve as such a triage marker. Four quantitative methylation\u2010specific PCRs (qMSP), two for CADM1 (regions M12 and M18) and MAL (regions M1 and M2) each, were applied to 261 cervical tissue specimens ranging from no neoplasia to carcinoma. When qMSPs were combined and positivity for at least one of the qMSPs in the combination was taken into account, the highest positivity rates for cervical intraepithelial neoplasia grade 3 (CIN3) lesions (97%) and squamous cell\u2010 and adeno\u2010carcinomas (99%) were obtained by combining a single CADM1 marker with a single MAL marker. Subsequent qMSP analysis of 70 GP5+\/6+\u2010PCR hrHPV\u2010positive scrapings revealed that a two\u2010marker panel consisting of CADM1\u2010M18 and MAL\u2010M1 was most discriminative, detecting 90% of women with CIN3 (\n                    <jats:italic>n<\/jats:italic>\n                    = 30), whereas it showed a positive result in only 13.5% of women without cervical disease (\n                    <jats:italic>n<\/jats:italic>\n                    = 40). Finally, we applied hrHPV GP5+\/6+\u2010PCR testing followed by CADM1\u2010M18\/MAL\u2010M1 methylation analysis to a cohort of 79 women visiting the outpatient colposcopy clinic. hrHPV testing revealed a sensitivity of 97% and a specificity of 33% for CIN3+. Additional CADM1\u2010M18\/MAL\u2010M1 methylation analysis on the hrHPV\u2010positive women increased the specificity to 78% with a sensitivity of 70%. In conclusion, the methylation marker panel CADM1\u2010M18 and MAL\u2010M1 may serve as an alternative molecular triage tool for hrHPV\u2010positive women.\n                  <\/jats:p>","DOI":"10.1002\/ijc.25890","type":"journal-article","created":{"date-parts":[[2010,12,28]],"date-time":"2010-12-28T09:31:55Z","timestamp":1293528715000},"page":"2218-2225","source":"Crossref","is-referenced-by-count":92,"title":["Combined CADM1 and MAL promoter methylation analysis to detect (pre\u2010)malignant cervical lesions in high\u2010risk HPV\u2010positive women"],"prefix":"10.1002","volume":"129","author":[{"given":"Ren\u00e9e M.","family":"Overmeer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Louwers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J.L.M.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert J.","family":"van Kemenade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertus T.","family":"Hesselink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie Fransen","family":"Daalmeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M.","family":"Wilting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle A.M.","family":"Heideman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 H.M.","family":"Verheijen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afra","family":"Zaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Marchien van Baal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Berkhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.F.","family":"Snijders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske D.M.","family":"Steenbergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,11]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61450-0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70360-2"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073204"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0096"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.10.012"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2598"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22060"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23258"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh031"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23519"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20425"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-3194"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-55"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0323"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2367"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20076"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/dc.10409"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2003.011841"},{"key":"e_1_2_6_20_2","unstructured":"Vereniging van Integrale Kankercentra. Dutch guideline: treatment of Cervical Intra\u2010epithelial Neoplasia (CIN) according to Werkgroep Oncologische Gyneacologie.2004. Available at:www.oncoline.nl."},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-271"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.3.791-795.1997"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.3.779-787.2002"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2888"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000049627.90307.4d"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604777"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10464"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji041"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2009.09.032"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2007.08.057"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.25890","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.25890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T09:16:24Z","timestamp":1697447784000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.25890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,11]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1002\/ijc.25890"],"URL":"https:\/\/doi.org\/10.1002\/ijc.25890","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,11]]}}}