Noninvasive evaluation of oral lesions using depth-sensitive optical spectroscopy

Abstract

Background: Optical spectroscopy is a noninvasive technique with potential applications for diagnosis of oral dysplasia and early cancer. In this study, we evaluated the diagnostic performance of a depth-sensitive optical spectroscopy (DSOS) system for distinguishing dysplasia and carcinoma from non-neoplastic oral mucosa.

Methods: Patients with oral lesions and volunteers without any oral abnormalities were recruited to participate. Autofluorescence and diffuse reflectance spectra of selected oral sites were measured using the DSOS system. A total of 424 oral sites in 124 subjects were measured and analyzed, including 154 sites in 60 patients with oral lesions and 270 sites in 64 normal volunteers. Measured optical spectra were used to develop computer-based algorithms to identify the presence of dysplasia or cancer. Sensitivity and specificity were calculated using a gold standard of histopathology for patient sites and clinical impression for normal volunteer sites.

Results: Differences in oral spectra were observed in: (1) neoplastic versus nonneoplastic sites, (2) keratinized versus nonkeratinized tissue, and (3) shallow versus deep depths within oral tissue. Algorithms based on spectra from 310 nonkeratinized anatomic sites (buccal, tongue, floor of mouth, and lip) yielded an area under the receiver operating characteristic curve of 0.96 in the training set and 0.93 in the validation set.

Conclusions: The ability to selectively target epithelial and shallow stromal depth regions appeared to be diagnostically useful. For nonkeratinized oral sites, the sensitivity and specificity of this objective diagnostic technique were comparable to that of clinical diagnosis by expert observers. Thus, DSOS has potential to augment oral cancer screening efforts in community settings.

FIGURE 1

Spectroscopic probe in contact with a measurement site.

FIGURE 2

Average spectra of non-keratinized tissue by diagnosis, illustrating differences in data obtained at different depths. Left column: fluorescence spectra at 350 nm excitation; arrows indicate absorption of fluorescent light by hemoglobin. Right column: reflectance spectra with white light illumination. Top, middle, and bottom: shallow, medium, and deep probe channels, respectively. An asterisk (*) next to a diagnostic category indicates that differences in the mean intensities of normal tissue and that diagnostic category were statistically significant (two-tailed Student’s t-test, P < 0.05 / 6, correcting for 6 comparisons per panel). Peak fluorescence intensity in the 390–650 nm region and reflectance intensity ratio at 420 nm were used in the statistical comparisons.

FIGURE 3

Diagnostic classification results. Left column: Non-keratinized training set (191 sites in 69 subjects). Right column: non-keratinized validation set (119 sites in 46 subjects). Top row: ROC curves for depth-sensitive spectroscopy; sensitivity and specificity values for clinical impression; and sensitivity and specificity values reported in the literature. Bottom row: Posterior probability values corresponding to the plotted ROC curves. Sensitivity and specificity of spectroscopy in the keratinized set (114 sites in 64 subjects) are also shown in (a). n: number of subjects. AUC: area under ROC curve.