This proposal is aimed at establishing Infrared Microspectroscopy (IR-MSP) as a faster, less expensive, more objective and more accurate technology for the detection of cervical dvsplasia than presently used methods. Screening for cervical disease is presently carried out via a cytological procedure (the Papanicolaou, or """"""""Pap"""""""" test), that was first proposed in the late 1940's [Papanicolaou, 1948]. Although regularly scheduled gynecological screening using the Pap test has reduced the incidence of, and mortality from, cervical cancer enormously, there remains a relatively high rate of inaccurate or inconclusive diagnoses [US Department of Health and Human Services, 1989]. Classical cytology is a visual inspection method based on locating and recognizing cells with altered morphology as an indicator of disease. The morphological changes are a consequence of cellular mutations. Although well established, this approach suffers from the fact that the interpretation of morphological change is human-based and therefore, subjective in nature. Furthermore, operator fatigue, training and experience influence the quality, reliability and reproducibility of cytological diagnoses. To alleviate the inherent limitation of visual inspection, computer based inspection by imaging technology has been developed and utilized over the past ten years. However, computer based image analysis has not significantly improved the reliability of the diagnoses, and has not proved cost effective [Hutchinson, 1996]. IR-MSP is a novel technique that recognizes abnormality by detecting cellular composition and variations therein, rather than by changes in morphological features. In fact, IR-MSP detects the precursor of the morphological change. The actual measurement carded out in IR-MSP is objective and quantifiable; consequently, the diagnostic method is more sensitive, specific, reproducible and reliable than existing methods. In this proposal, the methodology for IR-MSP testing of cervical smears will be developed, including the purification of the exfoliated cells, preparation of a cell monolayer on a suitable substrate, spectral imaging of about 104 individual cells via an infrared microspectrometer equipped with a focal plane array detector, and analysis of the collected data via multivariate statistical methods to arrive at a diagnosis. This work has the potential to improve cervical cancer screening by further reducing false positive and false negative diagnoses, and introducing fast and point-of-care routine screening tests.
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