Development and validation of a classification and scoring system for the diagnosis of oral squamous cell carcinomas through confocal laser endomicroscopy

dc.contributor.authorOetter, Nicolai
dc.contributor.authorKnipfer, Christian
dc.contributor.authorRohde, Maximilian
dc.contributor.authorvon Wilmowsky, Cornelius
dc.contributor.authorMaier, Andreas
dc.contributor.authorBrunner, Kathrin
dc.contributor.authorAdler, Werner
dc.contributor.authorNeukam, Friedrich-Wilhelm
dc.contributor.authorNeumann, Helmut
dc.contributor.authorStelzle, Florian
dc.description.abstractBackground Confocal laser endomicroscopy (CLE) is an optical biopsy method allowing in vivo microscopic imaging at 1000-fold magnification. It was the aim to evaluate CLE in the human oral cavity for the differentiation of physiological/carcinomatous mucosa and to establish and validate, for the first time, a scoring system to facilitate CLE assessment. Methods The study consisted of 4 phases: (1) CLE-imaging (in vivo) was performed after the intravenous injection of fluorescein in patients with histologically confirmed carcinomatous oral mucosa; (2) CLE-experts (n = 3) verified the applicability of CLE in the oral cavity for the differentiation between physiological and cancerous tissue compared to the gold standard of histopathological assessment; (3) based on specific patterns of tissue changes, CLE-experts (n = 3) developed a classification and scoring system (DOC-Score) to simplify the diagnosis of oral squamous cell carcinomas; (4) validation of the newly developed DOC-Score by non-CLE-experts (n = 3); final statistical evaluation of their classification performance (comparison to the results of CLE-experts and the histopathological analyses). Results Experts acquired and edited 45 sequences (260 s) of physiological and 50 sequences (518 s) of carcinomatous mucosa (total: 95 sequences/778 s). All sequences were evaluated independently by experts and non-experts (based on the newly proposed classification system). Sensitivity (0.953) and specificity (0.889) of the diagnoses by experts as well as sensitivity (0.973) and specificity (0.881) of the non-expert ratings correlated well with the results of the present gold standard of tissue histopathology. Experts had a positive predictive value (PPV) of 0.905 and a negative predictive value (NPV) of 0.945. Non-experts reached a PPV of 0.901 and a NPV of 0.967 with the help of the DOC-Score. Inter-rater reliability (Fleiss` kappa) was 0.73 for experts and 0.814 for non-experts. The intra-rater reliability (Cronbach’s alpha) of the experts was 0.989 and 0.884 for non-experts. Conclusions CLE is a suitable and valid method for experts to diagnose oral cancer. Using the DOC-Score system, an accurate chair-side diagnosis of oral cancer is feasible with comparable results to the gold standard of histopathology—even in daily clinical practice for non-experienced raters.en
dc.identifier.citationJournal of Translational Medicine 14 (2016). <>
dc.subjectConfocal laser endomicroscopy
dc.subjectOral squamous cell carcinoma
dc.subjectOral cancer
dc.subjectReal-time histology
dc.subjectOptical biopsy
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleDevelopment and validation of a classification and scoring system for the diagnosis of oral squamous cell carcinomas through confocal laser endomicroscopyen
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleJournal of Translational Medicine
local.subject.fakultaetMedizinische Fakultät
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2016
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