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Research Highlights
Non-Invasive Imaging of Oral Premalignancy and Malignancy
(Journal of Biomedical Optics 10, 51601)

H&E stained and in vivo OCT images of healthy hamster cheek pouch. In the
OCT images, multiple epithelial and subepithelial layers and presence or absence
of basement membrane are clearly visible: 1, keratinized surface layer; 2, flat
stratified squamous epithelium; 3, submucosa: dense fibrous connective tissue; 4,
longitudinal striated muscle fiber; and 5, basement membrane.

H&E stained and in vivo OCT images of dysplastic hamster pouch.

H&E stained and in vivo OCT images of malignant hamster cheek pouch.

Early detection of cancer and its precursors remains the best way to ensure patient survival and quality of life. Two basic facts indicate that early detection of oral malignancy should be possible to a far greater extent: 1. Accounting for 96% of all oral cancers, squamous cell carcinoma is usually preceded by dysplasia presenting as white, red, or mixed red and white epithelial lesions on the oral mucosa (leukoplakia, erythroplakia). Leukoplakias develop in 1 to 4% of the population. 2 Malignant transformation, which is quite unpredictable, occurs in 1 to 40% of leukoplakias over 5 yr. Dysplastic lesions in the form of erythroplakias carry a risk for malignant conversion2 of 90%. Thus, oral cancer is predominantly preceded by white or red lesions that are visible to the naked eye, and often present for a considerable period of time prior to transformation. A noninvasive diagnostic modality would enable monitoring of these lesions at regular intervals and detection of treatment needs at a very early, relatively harmless stage. 2. High-risk populations are clearly defined by tobacco use, alcohol abuse, urban environment, specific races, poor diet, and frequent exposure to sunlight.1-4. A fast, mobile, inexpensive noninvasive diagnostic modality would enable detection of oral lesions and of treatment needs at an early, relatively harmless stage.

The specific aim of this work was to test a multimodality approach to noninvasive diagnostics of oral premalignancy and malignancy. In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial, and vascular change throughout carcinogenesis. In vivo multiwavelength multiphoton (MPM) and second-harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by two blinded, prestandardized investigators using a scale from 0 to 6 for all modalities. After sacrifice, histopathology was evaluated on a scale of 0 to 6. Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2 mm. The sensitivity (OCT/ODT alone, 71 to 88%; OCT+MPM/SHG, 79 to 91%) and specificity (OCT alone, 62 to 83%; OCT+MPM/SHG, 67 to 90%) compare well with conventional techniques. Our conclusions are that OCT/ODT and MPM/SHG are promising noninvasive in vivo diagnostic modalities for oral dysplasia and malignancy.

LITERATURE

1. Cancer Facts and Figures, pp 4, American Cancer Society, 2000

2. Oral Pathology. Eds. Regezi J and Sciubba J. W.B.Saunders Co., Philadelphia (1993). 77-90.

3. California Department of Health Services. Cancer Surveillance Section Annual Report, March 1999.

4. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium. Cancer:6:963-8 (1953).

5. Kujan O, Glenny AM, Duxbury J, Thakker N, Sloan P. Evaluation of screening strategies for improving oral cancer mortality: a Cochrane systematic review. J Dent Educ. Feb;69(2):255-65. 2005.

 

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