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A quantitative Malignancy Index Diagnostic System (qMIDS) was developed based on 14 FOXM1 (isoform B)\u2010associated genes implicated in the regulation of the cell cycle, differentiation, ageing, genomic stability, epigenetic and stem cell renewal, and two reference genes. Their mRNA expression levels were translated via a prospectively designed algorithm, into a metric scoring system. Subjects from UK and Norway (<jats:italic>n<\/jats:italic> = 299) provided 359 head and neck tissue specimens. Diagnostic test performance was assessed using detection rate (DR) and false\u2010positive rate (FPR). The median qMIDS scores were 1.3, 2.9 and 6.7 in healthy tissue, dysplasia and head and neck squamous cell carcinomas (HNSCC), respectively (UK prospective dataset, p&lt;0.001); 1.4, 2.3 and 7.6 in unaffected, oral lichen planus, or HNSCC, respectively (Norwegian retrospective dataset with up to 19 years survival data, p&lt;0.001). At a qMIDS cut\u2010off of 4.0, DR was 94% and FPR was 3.2% (Norwegian dataset); and DR was 91% and FPR was 1.3% (UK dataset). We further demonstrated the transferability of qMIDS for diagnosing premalignant human vulva (<jats:italic>n<\/jats:italic> = 58) and skin (<jats:italic>n<\/jats:italic> = 21) SCCs, illustrating its potential clinical use for other cancer types. This study provided evidence that qMIDS was able to quantitatively diagnose and objectively stratify cancer aggressiveness. With further validation, qMIDS could enable early HNSCC detection and guide appropriate treatment. Early treatment intervention can lead to long\u2010term reduction in healthcare costs and improve patient outcome.<\/jats:p>","DOI":"10.1002\/ijc.27886","type":"journal-article","created":{"date-parts":[[2012,10,4]],"date-time":"2012-10-04T06:53:09Z","timestamp":1349333589000},"page":"2095-2106","source":"Crossref","is-referenced-by-count":33,"title":["Exploiting FOXM1\u2010orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis"],"prefix":"10.1002","volume":"132","author":[{"given":"Muy\u2010Teck","family":"Teh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L.","family":"Hutchison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela 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