Back
 AiM  Vol.6 No.2 , February 2016
A Candid Assessment of the Link between Oral Candida Containing Biofilms and Oral Cancer
Abstract: An association between Candida and oral cancer has long been discussed in the literature and in particular Candida albicans has been proposed to play a significant role in the development of oral cancer. Although this organism is a common member of the oral mucosa and can cause a variety of oral mucosal lesions, the exact mechanisms by which C. albicans potentially causes the development of malignant disease still require much research. We have undertaken an extensive literature search to understand pathogenicity of C. albicans, including its virulence factors, its interactions with the host immune, how a dysregulation of the immune response can result in malignancy, and how a potential C. albicans specific cytokine response may be involved in oral carcinogenesis. We present here a candid assessment of the role of Candida in oral carcinogenesis and a hypothetical model about how this may occur. Finally, we present potential future research which is necessary to elucidate this role.
Cite this paper: Kang, J. , He, Y. , Hetzl, D. , Jiang, H. , Jun, M. , Jun, M. , Khng, M. , Cirillo, N. and McCullough, M. (2016) A Candid Assessment of the Link between Oral Candida Containing Biofilms and Oral Cancer. Advances in Microbiology, 6, 115-123. doi: 10.4236/aim.2016.62012.
References

[1]   Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., et al. (2015) Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. International Journal of Cancer (Journal International du Cancer), 136, E359-E386.

[2]   Bakri, M.M., Hussaini, H.M., Holmes, A.R., Cannon, R.D. and Rich, A.M. (2010) Revisiting the Association between Candidal Infection and Carcinoma, Particularly Oral Squamous Cell Carcinoma. Journal of Oral Microbiology, 2, 1.

[3]   Williamson, D.M. (1969) Chronic Hyperplastic Candidiasis and Squamous Carcinoma. British Journal of Dermatology, 81, 125-127.
http://dx.doi.org/10.1111/j.1365-2133.1969.tb15992.x

[4]   Cawson, R. (1969) Leukoplakia and Oral Cancer. Proceedings of the Royal Society of Medicine, 62, 610.

[5]   Gall, F., Colella, G., Di Onofrio, V., Rossiello, R., Angelillo, I.F. and Liguori, G. (2013) Candida spp. in Oral Cancer and Oral Precancerous Lesions. New Microbiol, 36, 283-288.

[6]   Sanjaya, P., Gokul, S., Patil, B.G. and Raju, R. (2011) Candida in Oral Pre-Cancer and Oral Cancer. Medical Hypotheses, 77, 1125-1128.
http://dx.doi.org/10.1016/j.mehy.2011.09.018

[7]   Scully, C., Ei-Kabir, M. and Samaranayake, L.P. (1994) Candida and Oral Candidosis: A Review. Critical Reviews in Oral Biology & Medicine, 5, 125-57.

[8]   Reibel, J. (2003) Prognosis of Oral Pre-Malignant Lesions: Significance of Clinical, Histopathological, and Molecular Biological Characteristics. Critical Reviews in Oral Biology & Medicine, 14, 47-62.
http://dx.doi.org/10.1177/154411130301400105

[9]   Alnuaimi, A.D., O’Brien-Simpson, N.M., Reynolds, E.C. and McCullough, M.J. (2013) Clinical Isolates and Laboratory Reference Candida Species and Strains Have Varying Abilities to Form Biofilms. FEMS Yeast Research, 13, 689-699.
http://dx.doi.org/10.1111/1567-1364.12068

[10]   Thein, Z.M., Samaranayake, Y.H., Samaranayake, L.P. (2007) In Vitro Biofilm Formation of Candida albicans and Non-albicans Candida Species under Dynamic and Anaerobic Conditions. Archives of Oral Biology, 52, 761-767.
http://dx.doi.org/10.1016/j.archoralbio.2007.01.009

[11]   Mitchell, B.M., Wu, T.G., Jackson, B.E. and Wilhelmus, K.R. (2007) Candida albicans Strain-Dependent Virulence and Rim13p-Mediated Filamentation in Experimental Keratomycosis. Investigative Ophthalmology & Visual Science, 48, 774-780.
http://dx.doi.org/10.1167/iovs.06-0793

[12]   Jenkinson, H.F. and Douglas, L.J. (2002) Interactions between Candida Species and Bacteria in Mixed Infections. In: Brogden, K. and Guthmiller, J., Eds., Polymicrobial Diseases, ASM Press, Washington DC, 357-373.
http://dx.doi.org/10.1128/9781555817947.ch18

[13]   Akpan, A. and Morgan, R. (2002) Oral Candidiasis. Postgraduate Medical Journal, 78, 455-459.
http://dx.doi.org/10.1136/pmj.78.922.455

[14]   Nagy, K., Sonkodi, I., Szoke, I., Nagy, E. and Newman, H. (1998) The Microflora Associated with Human Oral Carcinomas. Oral Oncology, 34, 304-308.
http://dx.doi.org/10.1016/S1368-8375(98)80012-2

[15]   McCullough, M., Jaber, M., Barrett, A., Bain, L., Speight, P. and Porter, S. (2002) Oral Yeast Carriage Correlates with Presence of Oral Epithelial Dysplasia. Oral Oncology, 38, 391-393.
http://dx.doi.org/10.1016/S1368-8375(01)00079-3

[16]   Alnuaimi, A.D., Wiesenfeld, D., O’Brien-Simpson, N.M., Reynolds, E.C. and McCullough, M.J. (2015) Oral Candida Colonization in Oral Cancer Patients and Its Relationship with Traditional Risk Factors of Oral Cancer: A Matched Case-Control Study. Oral Oncology, 51, 139-145.
http://dx.doi.org/10.1016/j.oraloncology.2014.11.008

[17]   Arzmi, M., Alshwaimi, E., Harun, W.W., Razak, F.A., Farina, F., McCullough, M., et al. (2014) Gaining More Insight into the Determinants of Candida Species Pathogenicity in the Oral Cavity. European Journal of Inflammation, 12, 227-235.

[18]   Norgaard, M., Thomsen, R.W., Farkas, D.K., Mogensen, M.F. and Sorensen, H.T. (2013) Candida Infection and Cancer Risk: A Danish Nationwide Cohort Study. European Journal of Internal Medicine, 24, 451-455.
http://dx.doi.org/10.1016/j.ejim.2013.02.017

[19]   Rodriguez, M.J., Schneider, J., Moragues, M.D., Martinez-Conde, R., Ponton, J. and Aguirre, J.M. (2007) Cross-Reactivity between Candida albicans and Oral Squamous Cell Carcinoma Revealed by Monoclonal Antibody C7. Anticancer Research, 27, 3639-3643.

[20]   Talamini, R., Vaccarella, S., Barbone, F., Tavani, A., La Vecchia, C., Herrero, R., et al. (2000) Oral Hygiene, Dentition, Sexual Habits and Risk of Oral Cancer. British Journal of Cancer, 83, 1238-1242.
http://dx.doi.org/10.1054/bjoc.2000.1398

[21]   Sitheeque, M. and Samaranayake, L. (2003) Chronic Hyperplastic Candidosis/Candidiasis (Candidal Leukoplakia). Critical Reviews in Oral Biology & Medicine, 14, 253-267.
http://dx.doi.org/10.1177/154411130301400403

[22]   Naglik, J., Albrecht, A., Bader, O. and Hube, B. (2004) Candida albicans Proteinases and Host/Pathogen Interactions. Cellular Microbiology, 6, 915-926.
http://dx.doi.org/10.1111/j.1462-5822.2004.00439.x

[23]   Krogh, P. (1990) The Role of Yeasts in Oral Cancer by Means of Endogenous Nitrosation. Acta Odontologica, 48, 85-88.
http://dx.doi.org/10.3109/00016359009012738

[24]   Anderson, J.M. and Soll, D.R. (1987) Unique Phenotype of Opaque Cells in the White-Opaque Transition of Candida albicans. Journal of Bacteriology, 169, 5579-5588.

[25]   Jones, S., White, G. and Hunter, P. (1994) Increased Phenotypic Switching in Strains of Candida albicans Associated with Invasive Infections. Journal of Clinical Microbiology, 32, 2869-2870.

[26]   Vargas, K.G., Srikantha, R., Holke, A., Sifri, T., Morris, R. and Joly, S. (2004) Candida albicans Switch Phenotpes Display Differential Levels of Fitness. Medical Science Monitor, 10, BR198-BR206.

[27]   Williams, D. and Lewis, M. (2011) Pathogenesis and Treatment of Oral Candidosis. Journal of Oral Microbiology, 3, 1.
http://dx.doi.org/10.3402/jom.v3i0.5771

[28]   Sudbery, P., Gow, N. and Berman, J. (2004) The Distinct Morphogenic States of Candida albicans. Trends in Microbiology, 12, 317-324.
http://dx.doi.org/10.1016/j.tim.2004.05.008

[29]   Jackson, A.P., Gamble, J.A., Yeomans, T., Moran, G.P., Saunders, D., Harris, D., et al. (2009) Comparative Genomics of the Fungal Pathogens Candida dubliniensis and Candida albicans. Genome Research, 19, 2231-2244.
http://dx.doi.org/10.1101/gr.097501.109

[30]   Calderone, R.A. and Braun, P.C. (1991) Adherence and Receptor Relationships of Candida albicans. Microbiological Reviews, 55, 1-20.

[31]   Hazen, K.C. (1989) Participation of Yeast Cell Surface Hydrophobicity in Adherence of Candida albicans to Human Epithelial Cells. Infection and Immunity, 57, 1894-1900.

[32]   Cotter, G. and Kavanagh, K. (2000) Adherence Mechanisms of Candida albicans. British Journal of Biomedical Science, 57, 241-249.

[33]   Hojo, K., Nagaoka, S., Ohshima, T. and Maeda, N. (2009) Bacterial Interactions in Dental Biofilm Development. Journal of Dental Research, 88, 982-990.
http://dx.doi.org/10.1177/0022034509346811

[34]   Mayer, F.L., Wilson, D. and Hube, B. (2013) Candida albicans Pathogenicity Mechanisms. Virulence, 4, 119-128.
http://dx.doi.org/10.4161/viru.22913

[35]   Samaranayake, L., McCourtie, J. and MacFarlane, T. (1980) Factors Affecting the In-Vitro Adherence of Candida albicans to Acrylic Surfaces. Archives of Oral Biology, 25, 611-615.
http://dx.doi.org/10.1016/0003-9969(80)90076-X

[36]   Whibley, N. and Gaffen, S.L. (2014) Brothers in Arms: Th17 and Treg Responses in Candida albicans Immunity. PLoS Pathogens, 10, e1004456.
http://dx.doi.org/10.1371/journal.ppat.1004456

[37]   Moyes, D.L. and Naglik, J.R. (2011) Mucosal Immunity and Candida albicans Infection. Clinical and Developmental Immunology, 2011, Article ID: 346307.

[38]   Moyes, D.L., Runglall, M., Murciano, C., Shen, C., Nayar, D., Thavaraj, S., et al. (2010) A Biphasic Innate Immune MAPK Response Discriminates between the Yeast and Hyphal Forms of Candida albicans in Epithelial Cells. Cell Host & Microbe, 8, 225-235.
http://dx.doi.org/10.1016/j.chom.2010.08.002

[39]   Mantovani, A., Sozzani, S., Locati, M., Allavena, P. and Sica, A. (2002) Macrophage Polarization: Tumor-Associated Macrophages as a Paradigm for Polarized M2 Mononuclear Phagocytes. Trends in Immunology, 23, 549-555.
http://dx.doi.org/10.1016/S1471-4906(02)02302-5

[40]   Conti, H.R., Shen, F., Nayyar, N., Stocum, E., Sun, J.N., Lindemann, M.J., et al. (2009) Th17 Cells and IL-17 Receptor Signaling Are Essential for Mucosal Host Defense against Oral Candidiasis. The Journal of Experimental Medicine, 206, 299-311.
http://dx.doi.org/10.1084/jem.20081463

[41]   Byrd, A.S., O’Brien, X.M., Johnson, C.M., Lavigne, L.M. and Reichner, J.S. (2013) An Extracellular Matrix-Based Mechanism of Rapid Neutrophil Extracellular Trap Formation in Response to Candida albicans. The Journal of Immunology, 190, 4136-4148.
http://dx.doi.org/10.4049/jimmunol.1202671

[42]   Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
http://dx.doi.org/10.1016/j.cell.2011.02.013

[43]   Wroblewski, L.E., Peek, R.M. and Wilson, K.T. (2010) Helicobacter Pylori and Gastric Cancer: Factors That Modulate Disease Risk. Clinical Microbiology Reviews, 23, 713-739.
http://dx.doi.org/10.1128/CMR.00011-10

[44]   Shacter, E. and Weitzman, S.A. (2002) Chronic Inflammation and Cancer. Oncology, 16, 217-232.

[45]   Bacurele, P. and Henkel, T. (1994) Functions and Activation of NF-κB in the Immune System. Annual Review of Immunology, 28, 121-127.

[46]   Tripathi, P. and Aggarwal, A. (2006) NF-κB Transcription Factor: A Key Player in the Generation of Immune Response. Current Science, 90, 519-531.

[47]   Dolcet, X., Llobet, D., Pallares, J. and Matias-Guiu, X. (2005) NF-κB in Development and Progression of Human Cancer. Virchows Archiv, 446, 475-482.
http://dx.doi.org/10.1007/s00428-005-1264-9

[48]   Pikarsky, E., Porat, R.M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., et al. (2004) NF-κB Functions as a Tumour Promoter in Inflammation-Associated Cancer. Nature, 431, 461-466.
http://dx.doi.org/10.1038/nature02924

[49]   Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008) Cancer-Related Inflammation. Nature, 454, 436-444.
http://dx.doi.org/10.1038/nature07205

[50]   Edna, Z.P.C., Kodappully, S.S., Muthu, K.S., Frank, A. and Gautam, S. (2015) Analysis of the Intricate Relationship between Chronic Inflammation and Cancer. Biochemical Journal, 468, 1-15.
http://dx.doi.org/10.1042/BJ20141337

[51]   Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C. and Hermoso, M.A. (2014) Chronic Inflammation and Cytokines in the Tumor Microenvironment. Journal of Immunology Research, 2014, Article ID: 149185.

[52]   Guasch, G., Schober, M., Pasolli, H.A., Conn, E.B., Polak, L. and Fuchs, E. (2007) Loss of TGFβ Signaling Destabilizes Homeostasis and Promotes Squamous Cell Carcinomas in Stratified Epithelia. Cancer Cell, 12, 313-327.
http://dx.doi.org/10.1016/j.ccr.2007.08.020

[53]   Levy, L. and Hill, C.S. (2006) Alterations in Components of the TGF-β Superfamily Signaling Pathways in Human Cancer. Cytokine & Growth Factor Reviews, 17, 41-58.
http://dx.doi.org/10.1016/j.cytogfr.2005.09.009

[54]   Bierie, B. and Moses, H.L. (2006) TGF-β and Cancer. Cytokine & Growth Factor Reviews, 17, 29-40.
http://dx.doi.org/10.1016/j.cytogfr.2005.09.006

[55]   Spaccapelo, R., Romani, L., Tonnetti, L., Cenci, E., Mencacci, A., Del Sero, G., et al. (1995) TGF-Beta Is Important in Determining the in Vivo Patterns of Susceptibility or Resistance in Mice Infected with Candida albicans. The Journal of Immunology, 155, 1349-1360.

[56]   Westermarck, J. and Kahari, V.-M. (1999) Regulation of Matrix Metalloproteinase Expression in Tumor Invasion. The FASEB Journal, 13, 781-792.

[57]   Fan, H.-X., Li, H.-X., Chen, D., Gao, Z.-X. and Zheng, J.-H. (2012) Changes in the Expression of MMP2, MMP9, and ColIV in Stromal Cells in Oral Squamous Tongue Cell Carcinoma: Relationships and Prognostic Implications. Journal of Experimental & Clinical Cancer Research, 31, 90.
http://dx.doi.org/10.1186/1756-9966-31-90

[58]   Claveau, I., Mostefaoui, Y. and Rouabhia, M. (2004) Basement Membrane Protein and Matrix Metalloproteinase Deregulation in Engineered Human Oral Mucosa Following Infection with Candida albicans. Matrix Biology, 23, 477-486.
http://dx.doi.org/10.1016/j.matbio.2004.08.006

[59]   Hassona, Y., Cirillo, N., Heesom, K., Parkinson, E. and Prime, S. (2014) Senescent Cancer-Associated Fibroblasts Secrete Active MMP-2 That Promotes Keratinocyte Dis-Cohesion and Invasion. British Journal of Cancer, 111, 1230-1237.
http://dx.doi.org/10.1038/bjc.2014.438

 
 
Top