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However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Exploratory observational study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>44 hrHPV+women, with paired self\/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal).<\/jats:p><\/jats:sec><jats:sec><jats:title>Primary and secondary outcome measures<\/jats:title><jats:p>Methylation levels of<jats:italic>CADM1, MAL<\/jats:italic>and<jats:italic>miR124-2<\/jats:italic>analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology\/p16-Ki67 stain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In clinician-collected samples,<jats:italic>MAL<\/jats:italic>and<jats:italic>miR124-2<\/jats:italic>methylation levels were significantly higher with increasing grade of disease (p=0.0046\u2009and p&lt;0.0015, respectively).<jats:italic>miR124-2<\/jats:italic>was the best predictor of HSIL (area under the curve, AUC 0.819) while<jats:italic>MAL<\/jats:italic>of SCC (AUC 0.856). In self-collected samples,<jats:italic>MAL<\/jats:italic>best predicted HSIL (AUC 0.595) while<jats:italic>miR124-2<\/jats:italic>SCC (AUC 0.812). Combined<jats:italic>miR124-2\/MAL<\/jats:italic>methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples.<jats:italic>miR124-2\/MAL<\/jats:italic>plus HPV16\/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>miR124-2\/MAL<\/jats:italic>methylation is a potential triage strategy for the detection of HSIL\/SCC in low-income and middle-income country.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-081282","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T08:19:06Z","timestamp":1718871546000},"page":"e081282","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Performance of<i>CADM1, MAL<\/i>and<i>miR124-2<\/i>methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"isrctn13476702","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9167-1234","authenticated-orcid":false,"given":"Monica","family":"Molano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy A","family":"Machalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Garland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prisha","family":"Balgovind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza","family":"Haqshenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Munnull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G","family":"Badman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-9817","authenticated-orcid":false,"given":"John","family":"Bolnga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa Marie","family":"Cornall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Gabuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zure","family":"Kombati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Brotherton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Saville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hawkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kaldor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela Josephine","family":"Toliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-4822","authenticated-orcid":false,"given":"Andrew John","family":"Vallely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald L","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"2024082721104702000_14.6.e081282.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"2024082721104702000_14.6.e081282.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.16244"},{"key":"2024082721104702000_14.6.e081282.3","unstructured":"Ferlay J , Ervik M , Lam F , et al . 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