Cervical cancer is the second most common malignancy among women worldwide. It is estimated that in 2007, 3,670 deaths will occur in the United States alone from this disease and 11,150 new cases of invasive cervical cancer will be diagnosed. Although early detection of cervical precancer has played a central role in reducing the mortality associated with this disease over the last 50 years, the incidence of pre-invasive squamous carcinoma of the cervix. When cervical cancers are detected early, they are highly curable. Existing screening and detection techniques, the Pap smear and colposcopy, have several deficiencies that prevent efficient management of an otherwise controllable disease. An automated diagnostic method with improved sensitivity and specificity that could allow for a """"""""See and Treat"""""""" protocol would significantly improve the management of the disease. This proposal seeks to prove the hypothesis that Raman spectroscopy, can provide differential diagnosis of cervical precancers, both high and low grade from inflammation, squamous metaplasia and normal areas of the cervix. The main objective of this proposal is to characterize and validate that low grade lesions can be differentiate from high grade lesions as well as the normal cervix and that this diagnosis can be performed regardless of the menopausal status of the patient. This will be accomplished by conducting a large clinical investigation, collecting Raman spectra from both normal and diseases cervix, separating them by histological category and classifying them via a multi-class discrimination algorithm. Additionally, with the development of a unique model for tissue spectral signatures, we seek to use this model to understand the disease process as it applies to optical spectroscopy. Finally, the system will be updated to be as compact as possible and the software developed to be """"""""easy"""""""" (one click collection and classification of a spectra) for clinical use. The results of the proposed work will have a significant impact on health care by providing the potential for complete disease management with a single detection tool. This would result in improved patient care and cost-effectiveness. With the success of this technique, Raman spectroscopy can be applied to other organ sites such as the prostate and ovary as well as other diseases thus impacting a broader field in medicine.

Public Health Relevance

Cervical cancer is the second most common type of cancer among women worldwide. Early detection of cervical precancer is the key to proper treatment of the disease before it becomes a cancer. Methods of detecting cervical precancer used today are limited in their ability to identify low and high grade disease from other non-normal conditions. This proposal presents a method for detecting cervical precancers in real time to guide treatment. Raman spectroscopy has the potential to be a more accurate and less expensive method of screening and diagnosing cervical dysplasia. The ability of Raman spectroscopy to enable a """"""""see and treat"""""""" protocol would decrease the number of return clinic visits and patient anxiety as the long waits for histopathology diagnoses would be eliminated. Thus, the technology has the potential to increase access to underserved populations where follow-up to screening may not be available. The technology poses no known risks to the patient, and therefore could be a safe alternative to current screening methods.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Rasooly, Avraham
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Vanderbilt University Medical Center
Schools of Medicine
United States
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O'Brien, Christine M; Vargis, Elizabeth; Rudin, Amy et al. (2018) In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy. Am J Obstet Gynecol 218:528.e1-528.e18
O'Brien, Christine M; Vargis, Elizabeth; Paria, Bibhash C et al. (2014) Raman spectroscopy provides a noninvasive approach for determining biochemical composition of the pregnant cervix in vivo. Acta Paediatr 103:715-21
Pence, Isaac J; Vargis, Elizabeth; Mahadevan-Jansen, Anita (2013) Assessing variability of in vivo tissue Raman spectra. Appl Spectrosc 67:789-800
Vargis, Elizabeth; Brown, Naoko; Williams, Kent et al. (2012) Detecting biochemical changes in the rodent cervix during pregnancy using Raman spectroscopy. Ann Biomed Eng 40:1814-24
Vargis, Elizabeth; Tang, Yi-Wei; Khabele, Dineo et al. (2012) Near-infrared Raman Microspectroscopy Detects High-risk Human Papillomaviruses. Transl Oncol 5:172-9
Vargis, Elizabeth; Byrd, Teresa; Logan, Quinisha et al. (2011) Sensitivity of Raman spectroscopy to normal patient variability. J Biomed Opt 16:117004
Vargis, Elizabeth; Kanter, Elizabeth M; Majumder, Shovan K et al. (2011) Effect of normal variations on disease classification of Raman spectra from cervical tissue. Analyst 136:2981-7
Kanter, Elizabeth M; Majumder, Shovan; Vargis, Elizabeth et al. (2009) Multiclass discrimination of cervical precancers using Raman spectroscopy. J Raman Spectrosc 40:205-211
Kanter, Elizabeth M; Majumder, Shovan; Kanter, Gary J et al. (2009) Effect of hormonal variation on Raman spectra for cervical disease detection. Am J Obstet Gynecol 200:512.e1-5
Kanter, Elizabeth M; Vargis, Elizabeth; Majumder, Shovan et al. (2009) Application of Raman spectroscopy for cervical dysplasia diagnosis. J Biophotonics 2:81-90

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