Background: Cervical cancer remains a major health problem, especially in developing\ncountries. Colposcopic examination is used to detect high-grade lesions in patients\nwith a history of abnormal pap smears. New technologies are needed to improve the\nsensitivity and specificity of this technique. We propose to test the potential of fluorescence\nconfocal microscopy to identify high-grade lesions.\nMethods: We examined the quantification of ex vivo confocal fluorescence microscopy\nto differentiate among normal cervical tissue, low-grade Cervical Intraepithelial\nNeoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology\nand tissue architecture features by analyzing images of cervical biopsies; and (2) determine\nthe accuracy of high-grade CIN detection via confocal microscopy relative to\nthe accuracy of detection by colposcopic impression. Forty-six biopsies obtained from\ncolposcopically normal and abnormal cervical sites were evaluated. Confocal images\nwere acquired at different depths from the epithelial surface and histological images\nwere analyzed using in-house software.\nResults: The features calculated from the confocal images compared well with those\nfeatures obtained from the histological images and histopathological reviews of the\nspecimens (obtained by a gynecologic pathologist). The correlations between two\nof these features (the nuclear-cytoplasmic ratio and the average of three nearest\nDelaunay-neighbors distance) and the grade of dysplasia were higher than that of\ncolposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing\nimages collected at the surface of the epithelium, and at 15 and 30 �¼m below the\nepithelial surface were respectively 100, 100, and 92 %.\nConclusions: Quantitative analysis of confocal fluorescence images showed its capacity\nfor discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal\ntissues, at different depth of imaging. This approach could be used to help clinicians\nidentify high-grade CIN in clinical settings.
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