The Application of Tissue Autofluorescence in Detection and Management of Oral Cancer and Premalignant Lesions

  • C.F. Poh
  • P. Lane
  • C. MacAulay
  • L. Zhang
  • M.P. Rosin


There is a wealth of literature that supports the use of tissue autofluorescence in the screening and diagnosis of precancers in the lung, uterine cervix, skin, and oral cavity. This approach is already in clinical use in the lung, and the mechanism of action of tissue autofluorescence has been well described in the cervix. Data are now emerging supporting its clinical usage in the detection and management of oral cancer and premalignant lesions. In this chapter, we will describe the biology underlying tissue autofluorescence, briefly review its current application in the management of lung and cervical cancers, and finally focus on its potential clinical utility in the detection and management of oral cancer and premalignant lesions.


Oral Cavity Oral Cancer Flavin Adenine Dinucleotide Premalignant Lesion Flavin Adenine Dinucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge the funding support from the National Institute of Dental and Craniofacial Research (R01DE13124 and R01DE17013), from the Canadian Institutes of Health Research (MOP-77663), and from the Canadian Cancer Society (CSS-20336) and a Clinician Scientist Award from the Canadian Institutes of Health Research and Scholar Award from Michael Smith Foundation for Health Research (C.F. Poh).


  1. R. D. Alvarez, T. C. Wright, and O. D. Grp, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecologic Oncology, vol. 106, pp. 23–28, 2007.CrossRefPubMedGoogle Scholar
  2. C. Baldwin, C. Garnis, L. Zhang, M. P. Rosin, and W. L. Lam, “Multiple microalterations detected at high frequency in oral cancer,” Cancer Research, vol. 65, pp. 7561–7, 2005.PubMedGoogle Scholar
  3. J. A. Brennan, L. Mao, R. H. Hruban, J. O. Boyle, Y. J. Eby, W. M. Koch, S. N. Goodman, and D. Sidransky, “Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck,” New England Journal of Medicine, vol. 332, pp. 429–35, 1995.CrossRefPubMedGoogle Scholar
  4. J. Califano, P. van der Riet, W. Westra, H. Nawroz, G. Clayman, S. Piantadosi, R. Corio, D. Lee, B. Greenberg, W. Koch, and D. Sidransky, “Genetic progression model for head and neck cancer: implications for field cancerization,” Cancer Research, vol. 56, pp. 2488–92, 1996.PubMedGoogle Scholar
  5. S. K. Chang, M. Follen, A. Malpica, U. Utzinger, G. Staerkel, D. Cox, E. N. Atkinson, C. MacAulay, and R. Richards-Kortum, “Optimal excitation wavelengths for discrimination of cervical neoplasia,” IEEE Transactions on Biomedical Engineering, vol. 49, pp. 1102–111, 2002.CrossRefPubMedGoogle Scholar
  6. T. Collier, D. Arifler, A. Malpica, M. Follen, and R. Richards-Kortum, “Determination of epithelial tissue scattering coefficient using confocal microscopy,” IEEE Journal of Selected Topics in Quantum Electronics, vol. 9, pp. 307–313, 2003.CrossRefGoogle Scholar
  7. J. D. Crissman and R. J. Zarbo, “Dysplasia, in situ carcinoma, and progression to invasive squamous cell carcinoma of the upper aerodigestive tract,” American Journal of Surgical Pathology, vol. 13 Suppl 1, pp. 5–16, 1989.PubMedGoogle Scholar
  8. T. DeSantis, N. Chakhtoura, L. Twiggs, D. Ferris, M. Lashgari, L. Flowers, M. Faupel, S. Bambot, S. Raab, and E. Wilkinson, “Spectroscopic imaging as a triage test for cervical disease: a prospective multicenter clinical trial,” Journal of Lower Genital Tract Disease, vol. 11, pp. 18–24, 2007.CrossRefPubMedGoogle Scholar
  9. I. J. Dhooge, M. De Vos, and P. B. Van Cauwenberge, “Multiple primary malignant tumors in patients with head and neck cancer: results of a prospective study and future perspectives,” Laryngoscope, vol. 108, pp. 250–6, 1998.CrossRefPubMedGoogle Scholar
  10. R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochemistry and Photobiology, vol. 73, pp. 636–41, 2001a.CrossRefPubMedGoogle Scholar
  11. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” Journal of Biomedical Optics, vol. 6, pp. 385–96, 2001b.CrossRefPubMedGoogle Scholar
  12. J. Ferlay, F. Bray, P. Pisani, and D. M. Parkin, “GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide,” IARC CancerBase No. 5. version 2.0 ed. Lyon: IARC Press, 2004.Google Scholar
  13. D. Fresko and S. S. Lazarus, “Oral carcinoma in situ. Its progression to squamous, basosquamous, and basal-cell carcinoma,” Archives of Pathology & Laboratory Medicine, vol. 105, pp. 15–9, 1981.Google Scholar
  14. C. Garnis, B. P. Coe, A. Ishkanian, L. Zhang, M. P. Rosin, and W. L. Lam, “Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer,” Genes Chromosomes Cancer, vol. 39, pp. 93–8, 2004.CrossRefPubMedGoogle Scholar
  15. A. Gillenwater, R. Jacob, R. Ganeshappa, B. Kemp, A. K. El-Naggar, J. L. Palmer, G. Clayman, M. F. Mitchell, and R. Richards-Kortum, “Noninvasive diagnosis of oral neoplasia based on fluorescence spectroscopy and native tissue autofluorescence,” Archives of Otolaryngology-Head & Neck Surgery, vol. 124, pp. 1251–8, 1998.Google Scholar
  16. D. Goldenberg, S. Harden, B. G. Masayesva, P. Ha, N. Benoit, W. H. Westra, W. M. Koch, D. Sidransky, and J. A. Califano, “Intraoperative molecular margin analysis in head and neck cancer,” Archives of Otolaryngology–Head & Neck Surgery, vol. 130, pp. 39–44, 2004.CrossRefGoogle Scholar
  17. J. R. Hayward and J. A. Regezi, “Oral dysplasia and in situ carcinoma: clinicopathologic correlations of eight patients,” Journal of Oral Surgery, vol. 35, pp. 756–62, 1977.PubMedGoogle Scholar
  18. D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem Photobiol, vol. 72, pp. 103–13, 2000.CrossRefPubMedGoogle Scholar
  19. K. J. Heppner, L. M. Matrisian, R. A. Jensen, and W. H. Rodgers, “Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response,” American Journal of Pathology, vol. 149, pp. 273–82, 1996.PubMedGoogle Scholar
  20. W. N. Hittelman, H. J. Kim, J. S. Lee, D. M. Shin, S. M. Lippman, J. Kim, J. Y. Ro, and W. K. Hong, “Detection of chromosome instability of tissue fields at risk: in situ hybridization,” Journal of Cellular Biochemistry. Supplement, vol. 25, pp. 57–62, 1996.CrossRefPubMedGoogle Scholar
  21. D. R. Ingrams, J. K. Dhingra, K. Roy, D. F. Perrault, I. D. Bottrill, S. Kabani, E. E. Rebeiz, M. M. Pankratov, S. M. Shapshay, R. Manoharan, I. Itzkan, and M. S. Feld, “Autofluorescence characteristics of oral mucosa,” Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, vol. 19, pp. 27–32, 1997.Google Scholar
  22. H. Kato and D. A. Cortese, “Early detection of lung-cancer by means of hematoporphyrin derivative fluorescence and laser photoradiation,” Clinics in Chest Medicine, vol. 6, pp. 237–53, 1985.PubMedGoogle Scholar
  23. T. C. Kennedy, S. Lam, and F. R. Hirsch, “Review of recent advances in fluorescence bronchoscopy in early localization of central airway lung cancer,” Oncologist, vol. 6, pp. 257–62, 2001.CrossRefPubMedGoogle Scholar
  24. S. Lam, T. Kennedy, M. Unger, Y. E. Miller, D. Gelmont, V. Rusch, B. Gipe, D. Howard, J. C. LeRiche, A. Coldman, and A. F. Gazdar, “Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy,” Chest, vol. 113, pp. 696–702, 1998.CrossRefPubMedGoogle Scholar
  25. S. Lam, C. MacAulay, J. Hung, J. LeRiche, A. E. Profio, and B. Palcic, “Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device,” Journal of Thoracic and Cardiovascular Surgery, vol. 105, pp. 1035–40, 1993.PubMedGoogle Scholar
  26. P. M. Lane, T. Gilhuly, P. Whitehead, H. Zeng, C. F. Poh, S. Ng, P. M. Williams, L. Zhang, M. P. Rosin, and C. E. MacAulay, “Simple device for the direct visualization of oral-cavity tissue fluorescence,” Journal of Biomedical Optics, vol. 11, pp. 024006, 2006.CrossRefPubMedGoogle Scholar
  27. D. M. Laronde, J. L. Bottorff, T. G. Hislop, C. Y. Poh, B. Currie, P. M. Williams, and M. P. Rosin, “Voices from the community–experiences from the dental office: initiating oral cancer screening,” Journal of the Canadian Dental Association, vol. 74, pp. 239–41, 2008.Google Scholar
  28. C. R. Leemans, R. Tiwari, J. J. Nauta, I. van der Waal, and G. B. Snow, “Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor,” Cancer, vol. 73, pp. 187–90, 1994.CrossRefPubMedGoogle Scholar
  29. H. Lui, S. Said, L. Warshawski, D. Zloty, D. McLean, C. MacAulay, and H. Zeng, “Fluorescence visualization with blue light more accurately estimates the histopathologic margins of basal cell carcinoma as compared to clinical examination alone,” presented at European Conferences on Biomedical Optics, Munich, Germany, 2001.Google Scholar
  30. A. Mashberg and A. M. Samit, “Early detection, diagnosis, and management of oral and oropharyngeal cancer,” CA: A Cancer Journal for Clinicians, vol. 39, pp. 67–88, 1989.CrossRefGoogle Scholar
  31. J. McMahon, C. J. O'Brien, I. Pathak, R. Hamill, E. McNeil, N. Hammersley, S. Gardiner, and E. Junor, “Influence of condition of surgical margins on local recurrence and disease-specific survival in oral and oropharyngeal cancer,” British Journal of Oral & Maxillofacial Surgery, vol. 41, pp. 224–31, 2003.CrossRefGoogle Scholar
  32. J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” Journal of Biomedical Optics, vol. 5, pp. 131–7, 2000.CrossRefPubMedGoogle Scholar
  33. M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer, vol. 97, pp. 1681–92, 2003.CrossRefPubMedGoogle Scholar
  34. A. Nath, K. Rivoire, S. Chang, L. West, S. B. Cantor, K. Basen-Engquist, K. Adler-Storthz, D. D. Cox, E. N. Atkinson, G. Staerkel, C. Macaulay, R. Richards-Kortum, and M. Follen, “A pilot study for a screening trial of cervical fluorescence spectroscopy,” International Journal of Gynecological Cancer, vol. 14, pp. 1097–107, 2004.CrossRefPubMedGoogle Scholar
  35. B. Palcic, S. Lam, J. Hung, and C. Macaulay, “Detection and localization of early lung-cancer by imaging techniques,” Chest, vol. 99, pp. 742–3, 1991.CrossRefPubMedGoogle Scholar
  36. M. F. Parker, G. C. Mooradian, G. S. Okimoto, D. M. O'Connor, K. Miyazawa, and S. J. Saggese, “Initial neural net construction for the detection of cervical intraepithelial neoplasia by fluorescence imaging,” American Journal of Obstetrics and Gynecology, vol. 187, pp. 398–402, 2002.CrossRefPubMedGoogle Scholar
  37. M. Partridge, S. Pateromichelakis, E. Phillips, G. G. Emilion, R. P. A’Hern, and J. D. Langdon, “A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization,” Cancer Research, vol. 60, pp. 3893–8, 2000.PubMedGoogle Scholar
  38. I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, “Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy,” Photochemistry and Photobiology, vol. 77, pp. 550–5, 2003.CrossRefPubMedGoogle Scholar
  39. I. Pavlova, M. Williams, A. El-Naggar, R. Richards-Kortum, and A. Gillenwater, “Understanding the biological basis of autofluorescence imaging for oral cancer detection: high-resolution fluorescence microscopy in viable tissue,” Clinical Cancer Research, vol. 14, pp. 2396–404, 2008.CrossRefPubMedGoogle Scholar
  40. C. F. Poh, G. Hislop, B. Currie, R. Lee, S. Sikorski, C. Zed, L. Zhang, C. Macaulay, and M. P. Rosin, “Oral cancer screening in a high-risk underserved community–Vancouver Downtown Eastside,” Journal of Health Care for the Poor and Underserved, vol. 18, pp. 767–78, 2007a.PubMedGoogle Scholar
  41. C. F. Poh, S. P. Ng, P. M. Williams, L. Zhang, D. M. Laronde, P. Lane, C. Macaulay, and M. P. Rosin, “Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device,” Head Neck, vol. 29, pp. 71–6, 2007b.CrossRefPubMedGoogle Scholar
  42. C. F. Poh, L. Zhang, D. W. Anderson, J. S. Durham, P. M. Williams, R. W. Priddy, K. W. Berean, S. Ng, O. L. Tseng, C. MacAulay, and M. P. Rosin, “Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients,” Clinical Cancer Research, vol. 12, pp. 6716–22, 2006.CrossRefPubMedGoogle Scholar
  43. N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richardskortum, “In-vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, pp. 10193–7, 1994.Google Scholar
  44. R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annual Review of Physical Chemistry, vol. 47, pp. 555–606, 1996.CrossRefPubMedGoogle Scholar
  45. M. P. Rosin, X. Cheng, C. Poh, W. L. Lam, Y. Huang, J. Lovas, K. Berean, J. B. Epstein, R. Priddy, N. D. Le, and L. Zhang, “Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia,” Clinical Cancer Research, vol. 6, pp. 357–62, 2000.PubMedGoogle Scholar
  46. M. P. Rosin, W. L. Lam, C. Poh, N. D. Le, R. J. Li, T. Zeng, R. Priddy, and L. Zhang, “3p14 and 9p21 loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites,” Cancer Research, vol. 62, pp. 6447–50, 2002.PubMedGoogle Scholar
  47. M. P. Rosin, C. F. Poh, M. Guillard, P. M. Williams, L. Zhang, and C. MacAulay, “Visualization and other emerging technologies as change makers for oral cancer prevention,” Annals of the New York Academy of Sciences, vol. 1098, pp. 1–17, 2007.CrossRefGoogle Scholar
  48. S. Silverman, Jr. and M. Gorsky, “Epidemiologic and demographic update in oral cancer: California and national data–1973 to 1985,” Journal of the American Dental Association, vol. 120, pp. 495–9, 1990.PubMedGoogle Scholar
  49. D. P. Slaughter, H. W. Southwick, and W. Smejkal, “Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin,” Cancer, vol. 6, pp. 963–8, 1953.CrossRefPubMedGoogle Scholar
  50. K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, “Realistic three-dimensional epithelial tissue phantoms for biomedical optics,” Journal of Biomedical Optics, vol. 7, pp. 148–56, 2002.CrossRefPubMedGoogle Scholar
  51. D. J. Summerlin, “Precancerous and cancerous lesions of the oral cavity,” Dermatologic Clinics, vol. 14, pp. 205–23, 1996.CrossRefPubMedGoogle Scholar
  52. D. N. Sutton, J. S. Brown, S. N. Rogers, E. D. Vaughan, and J. A. Woolgar, “The prognostic implications of the surgical margin in oral squamous cell carcinoma,” International Journal of Oral and Maxillofacial Surgery, vol. 32, pp. 30–4, 2003.CrossRefPubMedGoogle Scholar
  53. E. Svistun, R. Alizadeh-Naderi, A. El-Naggar, R. Jacob, A. Gillenwater, and R. Richards-Kortum, “Vision enhancement system for detection of oral cavity neoplasia based on autofluorescence,” Head and Neck, vol. 26, pp. 205–15, 2004.CrossRefPubMedGoogle Scholar
  54. M. P. Tabor, R. H. Brakenhoff, H. J. Ruijter-Schippers, J. A. Kummer, C. R. Leemans, and B. J. Braakhuis, “Genetically altered fields as origin of locally recurrent head and neck cancer: a retrospective study,” Clinical Cancer Research, vol. 10, pp. 3607–13, 2004.CrossRefPubMedGoogle Scholar
  55. M. P. Tabor, R. H. Brakenhoff, V. M. van Houten, J. A. Kummer, M. H. Snel, P. J. Snijders, G. B. Snow, C. R. Leemans, and B. J. Braakhuis, “Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications,” Clinical Cancer Research, vol. 7, pp. 1523–32, 2001.PubMedGoogle Scholar
  56. G. T. Thomas, M. P. Lewis, and P. M. Speight, “Matrix metalloproteinases and oral cancer,” Oral Oncology, vol. 35, pp. 227–33, 1999.CrossRefPubMedGoogle Scholar
  57. H. Zeng, D. I. McLean, C. MacAulay, and H. Lui, “Autofluorescence properties of skin and applications in dermatology,” Proceedings of the SPIE – The International Society for Optical Engineering Biomedical Photonics and Optoelectronic Imaging, 8–10 Nov. 2000, vol. 4224, pp. 366–73, 2000.Google Scholar
  58. L. Zhang, S. Ng, C. F. Poh, P. M. Williams, D. M. Laronde, C. MacAulay, and M. P. Rosin, “Fluorescence visualization identifies primary oral premalignant lesions (OPL) with high-risk molecular patterns,” presented at the 99th Annual Meeting of the American Association for Cancer Research, San Diego, 2008.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • C.F. Poh
    • 1
  • P. Lane
    • 2
  • C. MacAulay
    • 2
  • L. Zhang
    • 1
  • M.P. Rosin
    • 3
  1. 1.Cancer Control Research and Cancer Imaging, BC Cancer Agency/Cancer Research CentreUniversity of British ColumbiaVancouverCanada
  2. 2.Cancer ImagingBC Cancer Agency/Cancer Research CentreVancouverCanada
  3. 3.Cancer Control Research, BC Cancer Agency/Cancer Research Centre, Biomedical Physiology & KinesiologySimon Fraser UniversityVancouverCanada

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