Chewing or smoking tobacco is the main cause of oral cancer, a condition which claims the lives of 10,000 people each year, more than cervical cancer or malignant melanoma.. Because of the difficulty in detecting oral cancer early, it has one of the worst survival rates of all cancers, less than 50% of patients survive more than 5 years after diagnosis. Yet, if it is detected and treated early, survival of oral cancer is better than those of most cancers. Thus, clinicians urgently need new tools for the early detection of cancerous changes in the mouth.
Lasers are a promising tool for the early detection of precancerous and cancerous conditions. Current diagnostic techniques involving observation, followed by biopsy (.surgical sampling) if signs of deterioration are apparent, often cannot achieve early detection of cancerous change. Cancerous changes in the mouth are not always visible to the naked eye. However, when cancerous tissues are subjected to some types of laser light, they may fluoresce (glow) compared to healthy, non-cancerous tissues. Furthermore, laser-induced fluorescence in tissue pre-treated with certain chemical agents (photosensitizers) which selectively localize in areas of precancer or cancer differs substantially between healthy and unhealthy tissues. ALA (5- Aminolevulinic acid) is a photosensitizer which can be applied topically and locally to the tissues of the mouth without many of the general side-effects of earlier photosensitizers.
We propose to investigate the use of fluorescence for the non-invasive (non surgical), early diagnosis of potential precancers (leukoplakias) and cancers (squamous cell carcinoma). This will be done in hamster cheek pouches, which best simulate conditions in the human mouth. Both autofluorescence (the tissue s own fluorescence under laser light) and the tissue's fluorescence under laser light after the application of ALA will be studied.
Fluorescence measurements will be performed in healthy, precancerous, and cancerous hamster cheeks using a fiber optic technology we have developed with funding from the National Institutes of Health/National Cancer Institute. This portable device features a thin fiber bundle which is introduced into the open mouth and hand-held near the tissue which is to be assessed. Laser light will pass through components of this fiber bundle into the mouth; fluorescence from the tissues will be collected by a tiny detector at the end ot the fiber bundle and pass back up to the body of the device through the fiber bundle. Thus, measurement will be non-invasive, quick, easy, and painless.
This work will provide the basis for clinical studies and the development of an improved diagnostic capability for dentists and physicians. As the occurrence of oral cancer rise (due to increased tobacco and alcohol abuse, and greater longevity), the need for early detection methods becomes more urgent. Through early, non-invasive detection of malignant transformation, the unpleasant side effects of biopsies are avoided, the devastating effects of the tumor and its treatment minimized, and treatment costs greatly reduced. While the emphasis of this proposal is on oral cancer, adaptation of this technique to gynecological and gastrointestinal diagnostics, and its extension to photodynamic cancer treatment in many medical specialties is also possible. |