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Two cohorts were included: a cohort of WLHIV<\/jats:styled-content> who were invited for cervical screening (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n\u00a0<\/jats:italic>=\u00a0<\/jats:italic>108, 60% HIV<\/jats:styled-content> seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL<\/jats:styled-content>1<\/jats:italic>, LHX<\/jats:styled-content>8<\/jats:italic> and ST<\/jats:styled-content>6GALNAC<\/jats:styled-content>5<\/jats:italic> by multiplex quantitative methylation specific PCR<\/jats:styled-content> (qMSP<\/jats:styled-content>). Histology endpoints were available for all study subjects.<\/jats:p><\/jats:sec>Results<\/jats:title>Hypermethylation levels of ASCL<\/jats:styled-content>1<\/jats:italic>, LHX<\/jats:styled-content>8<\/jats:italic> and ST<\/jats:styled-content>6GALNAC<\/jats:styled-content>5<\/jats:italic> increased with severity of cervical disease. The performance for detection of CIN<\/jats:styled-content>3 or worse (CIN<\/jats:styled-content>3+<\/jats:sup>) as assessed by the area under the receiver operating characteristic (ROC<\/jats:styled-content>) curves (AUC<\/jats:styled-content>) was good for ASCL<\/jats:styled-content>1<\/jats:italic> and LHX<\/jats:styled-content>8<\/jats:italic> (AUC<\/jats:styled-content> 0.79 and 0.81 respectively), and moderate for ST<\/jats:styled-content>6GALNAC<\/jats:styled-content>5<\/jats:italic> (AUC<\/jats:styled-content> 0.71). At a threshold corresponding to 75% specificity, CIN<\/jats:styled-content>3+<\/jats:sup> sensitivity was 72.1% for ASCL<\/jats:styled-content>1<\/jats:italic> and 73.8% for LHX<\/jats:styled-content>8<\/jats:italic> and all samples from women with cervical cancer scored positive for these two markers.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Hypermethylation analysis of ASCL<\/jats:styled-content>1<\/jats:italic> or LHX<\/jats:styled-content>8<\/jats:italic> in cervical scrape material of WLHIV<\/jats:styled-content> detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN<\/jats:styled-content>3+<\/jats:sup>, warranting further exploration of these methylation markers as a stand\u2010alone test for cervical screening in low\u2010resource settings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25165","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T08:33:03Z","timestamp":1534149183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Detection of hypermethylated genes as markers for cervical screening in women living with HIV"],"prefix":"10.1002","volume":"21","author":[{"given":"Wieke W","family":"Kremer","sequence":"first","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjolein","family":"Van Zummeren","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Putri W","family":"Novianti","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"},{"name":"Department of Epidemiology and Biostatistics VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin L","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Medical Virology University of Pretoria and National Health Laboratory Services Pretoria South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wina","family":"Verlaat","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter JF","family":"Snijders","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani\u00eblle AM","family":"Heideman","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renske DM","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greta","family":"Dreyer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University of Pretoria Pretoria South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-9463","authenticated-orcid":false,"given":"Chris JLM","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199711063371903"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp205"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0956462413491735"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1438.2001.01022.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.9613"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001367"},{"key":"e_1_2_8_8_1","unstructured":"UNAIDS.Prevention Gap Report. 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