{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:06:05Z","timestamp":1740103565100,"version":"3.37.3"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C569\/A10404"],"award-info":[{"award-number":["C569\/A10404"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:p>Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter\u2010reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (<jats:italic>i<\/jats:italic>) p16\u2010mRNA assay and (<jats:italic>ii<\/jats:italic>) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high\u2010risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT\u2010qPCR (p16\u2010mRNA assay) was run on mRNA extracted from formalin\u2010fixed paraffin\u2010embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high\u2010resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2\/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61\u201377) for 85% (95%CI 77\u201391%) sensitivity. The four\u2010point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71\u20130.82), compared with 0.71 (95%CI 0.64\u20130.77) for p16\u2010mRNA and 0.67 (95%CI 0.60\u20130.74) for Digital IHC. Spearman rank\u2010order correlations were: visual to p16\u2010mRNA 0.41, visual to digital 0.49 and p16\u2010mRNA to digital: 0.22. The addition of p16\u2010mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0049). p16\u2010mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists.<\/jats:p>","DOI":"10.1002\/ijc.30783","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T10:08:48Z","timestamp":1494929328000},"page":"829-836","source":"Crossref","is-referenced-by-count":6,"title":["Role of quantitative p16<sup>INK4A<\/sup> mRNA assay and digital reading of p16<sup>INK4A<\/sup> immunostained sections in diagnosis of cervical intraepithelial neoplasia"],"prefix":"10.1002","volume":"141","author":[{"given":"Nata\u0161a","family":"Vasiljevi\u0107","sequence":"first","affiliation":[{"name":"Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen 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