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Detecting Cervical Dysplasia in Minority Populations with Raman Spectroscopy

Objectives: Cervical cancer is the second most common malignancy among women worldwide. A "See and Treat" protocol with adequate sensitivity and specificity would significantly improve this disease's management in low-resource settings. 

Methods: Over the past few years, our laboratories have developed a probe-based instrument to acquire Raman spectra from the cervix (see Figure).  Raman spectroscopy uses light to measure the vibrational and rotational properties of bonds found in a variety of biomolecules.  It is a molecular specific technique that can provide detailed information about the biochemical composition of a tissue sample.  Patients undergoing a Pap smear or colposcopy-guided biopsy are recruited to this study under informed consent.  For the Pap smear patients, the sterilized probe is placed directly onto the cervix in various locations for 2-3 seconds.  For the colposcopy-guided biopsy patients, the probe is placed in one normal area and any area(s) the doctor decides to biopsy.  We have acquired Raman spectra from the cervix and developed a sophisticated algorithm to classify tissue as normal (benign or inflammatory), metaplasia, low-grade, or high-grade dysplasia.

Results: Previous results from a Caucasian population show that our tool works with a sensitivity of 98% and a specificity of 96%, with high-grade spectra classifying correctly 95% of the time and low-grade data classifying correctly 74% of the time.  Preliminary data analysis on a more diverse patient population shows more varied results, due to race/ethnicity and differing socioeconomic status.  Parsing the data based on these backgrounds leads to sensitivity, specificity, and classification rates closer to that found in a more homogenous Caucasian population.

Conclusions: The results of using this non-invasive tool that can be used directly on patients from varying socioeconomic and ethnic/racial backgrounds show its benefit in any place where professional care is difficult to achieve.

Key words: see and treat, optical diagnosis

Schematic

Schematic of system used to measure Raman Spectra (NF: notch filter, BP: band-pass filter, CCD: charge-coupled device).

References

Vargis E, Byrd T, Khabele D, A Mahadevan-Jansen.Using Raman Spectroscopy to detect cervical dysplasia in minority populations. Society of Gynecologic Oncologists.San Francisco, CA, March 2010.

Vargis E, Byrd T, Khabele D, A Mahadevan-Jansen.  Using Raman Spectroscopy to detect cervical dysplasia in minority populations.  SPIE: Photonics West 2010.  San Francisco, CA, January 2010.

Vargis E, Kanter EM, Kanter G, Rao Gautam, A Mahadevan-Jansen.  Proximity to disease has a significant impact on automated disease classification of normal tissues.  Society of Gynecologic Oncologists.  San Francisco, CA, March 2010.

Vargis E, Byrd T, Khabele D, A Mahadevan-Jansen.  Using Raman Spectroscopy to detect cervical dysplasia in minority populations. Society of Gynecologic Oncologists.  San Francisco, CA, March 2010.

Kanter EM, Vargis E, Majumder S, Beaven RB, Rao GG, A Mahadevan-Jansen.  Raman Spectroscopy for Cervical Precancer Detection.  Journal of Biomedical Optics.  (In Preparation), 2010.

Kanter EM, Vargis E, Majumder S, Keller MD, Beaven RB, Rao GG, A Mahadevan-Jansen. Application of Raman Spectroscopy for Cervical Dysplasia Diagnosis.  Journal of Biophotonics, 2: (1-2), 81-90, 2009.

Kanter EM, Majumder SK, Vargis E, Robichaux-Viehoever A, Kanter G, Shappell H, Jones III HW Mahadevan-Jansen A. Multi-class discrimination of cervical precancers using Raman spectroscopy, Journal of Raman Spectroscopy, 40(2), 205-211, 2009.

Kanter EM, Majumder S, Vargis E, Robichaux-Viehoever A, Kanter G, Shappell H, III Jones H, A Mahadevan-Jansen.  Multi-class discrimination of cervical precancers using Raman spectroscopy.  Journal of Raman Spectroscopy, 40: (2), 205-211, 2009.

Kanter EM, Vargis E, Majumder SK, Keller MD, Beaven RB, Rao GG, Mahadevan-Jansen A, Raman spectroscopy for cervical precancer detection. Gynecologic Oncology (in review), December 2008.

Keller MD, Kanter EM, Hutchings J, Kendal C, Stone N, Mahadevan-Jansen A, Spatial and temporal effects of cervical dysplasia as detected by Raman spectroscopy (invited paper), Disease Markers (in press), August 2008.

Vargis E, Kanter EM, Majumder S, Jones H III, A Mahadevan-Jansen. Cervical Cancer Detection with Raman Spectroscopy.  Vanderbilt-Ingram Cancer Center Retreat.  Nashville, TN, May 2008.

Vargis E, Kanter EM, Majumder SK, Jones HW III, Mahadevan-Jansen A, Cervical Cancer Detection with Raman Spectroscopy. SPEC 2008.  São José dos Campos, São Paulo, Brazil, October 2008.

Robichaux-Viehoever A, Kanter E, Shappell H, Billheimer D, Jones HW, Mahadevan-Jansen A, Characterization of Raman spectra measured in vivo for the detection of cervical dysplasia. Applied Spectroscopy, 61(9), 2007.

Keller MD, Kanter EM, Mahadevan-Jansen A, Raman spectroscopy for cancer diagnosis, Spectroscopy (Cover), 21 (11): 33-41, 2006.