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dc.contributor.authorCook, DAen_US
dc.contributor.authorKrajden, Men_US
dc.contributor.authorBrentnall, ARen_US
dc.contributor.authorGondara, Len_US
dc.contributor.authorChan, Ten_US
dc.contributor.authorLaw, JHen_US
dc.contributor.authorSmith, LWen_US
dc.contributor.authorvan Niekerk, DJen_US
dc.contributor.authorOgilvie, GSen_US
dc.contributor.authorColdman, AJen_US
dc.contributor.authorWarman, Ren_US
dc.contributor.authorReuter, Cen_US
dc.contributor.authorCuzick, Jen_US
dc.contributor.authorLorincz, ATen_US
dc.date.accessioned2018-11-19T10:42:48Z
dc.date.available2018-10-25en_US
dc.date.issued2018-11-09en_US
dc.date.submitted2018-11-13T16:57:39.333Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/51583
dc.description.abstractHuman papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case-control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25-65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4-98.0) and 41.8% (35.2-48.8), compared to 86.4% (75.0-95.7) and 49.8% (43.1-56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2-20.4) and 19.3% (16.6-22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens.en_US
dc.description.sponsorshipThe HPV FOCAL Trial was funded by the Canadian Institutes for Health Research (grant no. MCT82072). The methylation case-control study was funded by Cancer Research UK (grant no. C569/A10404).en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofInt J Canceren_US
dc.rights"This is the peer reviewed version of the following article: Cook, D. A., Krajden, M. , Brentnall, A. R., Gondara, L. , Chan, T. , Law, J. H., Smith, L. W., Niekerk, D. J., Ogilvie, G. S., Coldman, A. J., Warman, R. , Reuter, C. , Cuzick, J. and Lorincz, A. T. (2018), Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial. Int. J. Cancer. Accepted Author Manuscript. . doi:10.1002/ijc.31976 which will be published in final form at https://doi.org/10.1002/ijc.31976. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."
dc.subjectcervical canceren_US
dc.subjectcervical cancer screeningen_US
dc.subjectcolposcopy triageen_US
dc.subjecthuman papillomavirusen_US
dc.subjectmethylationen_US
dc.titleEvaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial.en_US
dc.typeArticle
dc.identifier.doi10.1002/ijc.31976en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30412281en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
dcterms.dateAccepted2018-10-25en_US


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