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

Journal of Translational Medicine

Research

Andreas Maier¹  Werner Adler²  Helmut Neumann³  Cornelius von Wilmowsky⁴  Nicolai Oetter⁴  Florian Stelzle⁵  Maximilian Rohde⁵  Friedrich-Wilhelm Neukam⁵  Christian Knipfer⁵  Kathrin Brunner⁶ 

[1] Department of Computer Science 5, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Martensstraße 3, 91058, Erlangen, Germany;SAOT-Erlangen Graduate School in Advanced Optical Technologies, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Paul Gordan Strasse 6, 91052, Erlangen, Germany;Department of Medical Information Technology, Biometry and Epidemiology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Waldstraße 6, 91054, Erlangen, Germany;Department of Medicine I, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany;SAOT-Erlangen Graduate School in Advanced Optical Technologies, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Paul Gordan Strasse 6, 91052, Erlangen, Germany;Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany;Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany;SAOT-Erlangen Graduate School in Advanced Optical Technologies, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Paul Gordan Strasse 6, 91052, Erlangen, Germany;Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany;

关键词: Confocal laser endomicroscopy;    CLE;    Oral squamous cell carcinoma;    OSCC;    Oral cancer;    DOC-score;    Real-time histology;    Optical biopsy;   

DOI  :  10.1186/s12967-016-0919-4

 received in 2016-01-13, accepted in 2016-05-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundConfocal 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.MethodsThe 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).ResultsExperts 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.ConclusionsCLE 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.

【 授权许可】

CC BY   
© The Author(s) 2016