Skip to main content
SpringerLink
Log in

Carcinogenesis and Field Cancerization in Oral Squamous Cell Carcinoma

  • Chapter
  • First Online:
Contemporary Oral Oncology

Abstract

Oral carcinogenesis is a multistep, multifocal process initiated as a consequence of carcinogenic insults on the oral mucosa in individuals with genetic susceptibility for oral cancer. The carcinogenic process results in successive molecular changes that lead to dysregulation of cell proliferation, growth, and differentiation. The changes at the genetic and molecular levels ultimately lead to cellular transformation and carcinogenesis. The carcinogenic process in oral cancer, as is the case with majority of other solid tumors, occurs stepwise fashion at molecular, histological, and clinical levels.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Reibel J. Prognosis of oral pre-malignant lesions: significance of clinical, histopathological, and molecular biological characteristics. Crit Rev Oral Biol Med. 2003;14(1):47–62.

    PubMed  Google Scholar 

  2. Feng J-Q, et al. Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer. J Oral Pathol Med. 2013;42(2):148–53.

    CAS  PubMed  Google Scholar 

  3. Axell T, et al. Oral white lesions with special reference to precancerous and tobacco-related lesions: conclusions of an international symposium held in Uppsala, Sweden, May 18-21 1994. International Collaborative Group on Oral White Lesions. J Oral Pathol Med. 1996;25(2):49–54.

    CAS  PubMed  Google Scholar 

  4. Reichart PA, Philipsen HP. Oral erythroplakia – a review. Oral Oncol. 2005;41(6):551–61.

    PubMed  Google Scholar 

  5. Silverman Jr S, Gorsky M. Proliferative verrucous leukoplakia: a follow-up study of 54 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(2):154–7.

    PubMed  Google Scholar 

  6. Zakrzewska JM, et al. Proliferative verrucous leukoplakia: a report of ten cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82(4):396–401.

    CAS  PubMed  Google Scholar 

  7. Lai DR, et al. Clinical evaluation of different treatment methods for oral submucous fibrosis. A 10-year experience with 150 cases. J Oral Pathol Med. 1995;24(9):402–6.

    CAS  PubMed  Google Scholar 

  8. Lian Ie B, Tseng YT, Su CC, Tsai KY. Progression of precancerous lesions to oral cancer: results based on the Taiwan National Health Insurance Database. Oral Oncol. 2013;49(5):427–30.

    PubMed  Google Scholar 

  9. Scully C, et al. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med. 1998;9(1):86–122.

    CAS  PubMed  Google Scholar 

  10. Silverman Jr S, Bahl S. Oral lichen planus update: clinical characteristics, treatment responses, and malignant transformation. Am J Dent. 1997;10(6):259–63.

    PubMed  Google Scholar 

  11. Speight PM. Update on oral epithelial dysplasia and progression to cancer. Head Neck Pathol. 2007;1(1):61–6.

    PubMed  PubMed Central  Google Scholar 

  12. Jagannathan N, Ramani P, Premkumar P, Natesan A, Sherlin HJ. Epithelial maturation pattern of dysplastic epithelium and normal oral epithelium exposed to tobacco and alcohol: a scanning electron microscopic study. Ultrastruct Pathol. 2013;37(3):171–5.

    PubMed  Google Scholar 

  13. Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W, Sidransky D. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 1996;56(11):2488–92.

    CAS  PubMed  Google Scholar 

  14. Braakhuis BJ, Leemans CR, Brakenhoff RH. A genetic progression model of oral cancer: current evidence and clinical implications. J Oral Pathol Med. 2004;33(6):317–22.

    CAS  PubMed  Google Scholar 

  15. Partridge M, Emilion G, Pateromichelakis S, A’Hern R, Phillips E, Langdon J. Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer. Oral Oncol. 1998;34(2):77–83.

    CAS  PubMed  Google Scholar 

  16. Zhou X, Jordan RC, Li Y, Huang BL, Wong DT. Frequent allelic imbalances at 8p and 11q22 in oral and oropharyngeal epithelial dysplastic lesions. Cancer Genet Cytogenet. 2005;161(1):86–9.

    CAS  PubMed  Google Scholar 

  17. Zhang L, Cheng X, Li Y, Poh C, Zeng T, Priddy R, Lovas J, Freedman P, Daley T, Rosin MP. High frequency of allelic loss in dysplastic lichenoid lesions. Lab Invest. 2000;80(2):233–7.

    CAS  PubMed  Google Scholar 

  18. Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, Berean K, Epstein JB, Priddy R, Le ND, Zhang L. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res. 2000;6(2):357–62.

    CAS  PubMed  Google Scholar 

  19. Chang SS, Califano J. Current status of biomarkers in head and neck cancer. J Surg Oncol. 2008;97(8):640–3.

    PubMed  Google Scholar 

  20. Graveland AP, Bremmer JF, de Maaker M, Brink A, Cobussen P, Zwart M, Braakhuis BJ, Bloemena E, van der Waal I, Leemans CR, Brakenhoff RH. Molecular screening of oral precancer. Oral Oncol. 2013;49(12):1129–35.

    CAS  PubMed  Google Scholar 

  21. Tabor MP, Braakhuis BJ, van der Wal JE, van Diest PJ, Leemans CR, Brakenhoff RH, Kummer JA. Comparative molecular and histological grading of epithelial dysplasia of the oral cavity and the oropharynx. J Pathol. 2003;199(3):354–60.

    CAS  PubMed  Google Scholar 

  22. Soni S, et al. Alterations of rb pathway components are frequent events in patients with oral epithelial dysplasia and predict clinical outcome in patients with squamous cell carcinoma. Oncology. 2005;68(4-6):314–25.

    CAS  PubMed  Google Scholar 

  23. Schoelch ML, Le QT, Silverman Jr S, McMillan A, Dekker NP, Fu KK, Ziober BL, Regezi JA. Apoptosis-associated proteins and the development of oral squamous cell carcinoma. Oral Oncol. 1999;35(1):77–85.

    CAS  PubMed  Google Scholar 

  24. Brennan PA, Conroy B, Spedding AV. Expression of inducible nitric oxide synthase and p53 in oral epithelial dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90(5):624–9.

    CAS  PubMed  Google Scholar 

  25. Cruz IB, et al. p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma. J Pathol. 1998;184(4):360–8.

    CAS  PubMed  Google Scholar 

  26. Shintani S, et al. Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity. Oral Oncol. 2002;38(3):235–43.

    CAS  PubMed  Google Scholar 

  27. Jordan RC, Bradley G, Slingerland J. Reduced levels of the cell-cycle inhibitor p27Kip1 in epithelial dysplasia and carcinoma of the oral cavity. Am J Pathol. 1998;152(2):585–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Schoelch ML, et al. Cell cycle proteins and the development of oral squamous cell carcinoma. Oral Oncol. 1999;35(3):333–42.

    CAS  PubMed  Google Scholar 

  29. Gologan O, Barnes EL, Hunt JL. Potential diagnostic use of p16INK4A, a new marker that correlates with dysplasia in oral squamoproliferative lesions. Am J Surg Pathol. 2005;29(6):792–6.

    PubMed  Google Scholar 

  30. Soria JC, et al. Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis. Br J Cancer. 2001;84(4):504–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Scambia G, Lovergine S, Masciullo V. RB family members as predictive and prognostic factors in human cancer. Oncogene. 2006;25(38):5302–8.

    CAS  PubMed  Google Scholar 

  32. Tanaka N, et al. pRb2/p130 protein expression is correlated with clinicopathologic findings in patients with oral squamous cell carcinoma. Cancer. 2001;92(8):2117–25.

    CAS  PubMed  Google Scholar 

  33. Tanaka N, et al. Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral mucosa. Oral Oncol. 2001;37(3):308–14.

    CAS  PubMed  Google Scholar 

  34. Lee JI, Soria JC, Hassan KA, El-Naggar AK, Tang X, Liu DD, Hong WK, Mao L. Loss of PTEN expression as a prognostic marker for tongue cancer. Arch Otolaryngol Head Neck Surg. 2001;127(12):1441–5.

    CAS  PubMed  Google Scholar 

  35. Torres-Rendon A, et al. Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas. Br J Cancer. 2009;100(7):1128–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Feng CJ, et al. Expression of Mcm7 and Cdc6 in oral squamous cell carcinoma and precancerous lesions. Anticancer Res. 2008;28(6A):3763–9.

    CAS  PubMed  Google Scholar 

  37. Gonzalez-Moles MA, et al. Suprabasal expression of Ki-67 antigen as a marker for the presence and severity of oral epithelial dysplasia. Head Neck. 2000;22(7):658–61.

    CAS  PubMed  Google Scholar 

  38. Iamaroon A, et al. Co-expression of p53 and Ki67 and lack of EBV expression in oral squamous cell carcinoma. J Oral Pathol Med. 2004;33(1):30–6.

    CAS  PubMed  Google Scholar 

  39. Kodani I, et al. Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa. Pathobiology. 2001;69(3):150–8.

    CAS  PubMed  Google Scholar 

  40. Abbas NF, et al. Immunohistochemical study of p53 and angiogenesis in benign and preneoplastic oral lesions and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(3):385–90.

    PubMed  Google Scholar 

  41. Pazouki S, et al. The association between tumour progression and vascularity in the oral mucosa. J Pathol. 1997;183(1):39–43.

    CAS  PubMed  Google Scholar 

  42. Gandolfo M, et al. Increased subepithelial vascularization and VEGF expression reveal potentially malignant changes in human oral mucosa lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111(4):486–93.

    PubMed  Google Scholar 

  43. Ravi D, et al. Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation. Oral Oncol. 1998;34(6):543–8.

    CAS  PubMed  Google Scholar 

  44. Shivamallappa SM, et al. Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study. Int J Oral Sci. 2011;3(4):216–24.

    PubMed  PubMed Central  Google Scholar 

  45. Li C, et al. Microvessel density and expression of vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived endothelial growth factor in oral squamous cell carcinomas. Int J Oral Maxillofac Surg. 2005;34(5):559–65.

    CAS  PubMed  Google Scholar 

  46. Kushner J, Bradley G, Jordan RC. Patterns of p53 and Ki-67 protein expression in epithelial dysplasia from the floor of the mouth. J Pathol. 1997;183(4):418–23.

    CAS  PubMed  Google Scholar 

  47. Xiaolian G, et al. p63 contributes to cell invasion and migration in squamous cell carcinoma of the head and neck. Cancer Lett. 2008;263.

    Google Scholar 

  48. Das RK, Pal M, Barui A, Paul RR, Chakraborty C, Ray AK, Sengupta S, Chatterjee J. Assessment of malignant potential of oral submucous fibrosis through evaluation of p63, E-cadherin and CD105 expression. J Clin Pathol. 2010;63(10):894–9.

    PubMed  Google Scholar 

  49. Wang Y, et al. Akt/Ezrin Tyr353/NF-kappaB pathway regulates EGF-induced EMT and metastasis in tongue squamous cell carcinoma. Br J Cancer. 2014;110(3):695–705.

    CAS  PubMed  Google Scholar 

  50. Villaret D, et al. Identification of genes overexpressed in head and neck squamous cell carcinoma using a combination of complementary DNA subtraction and microarray analysis. Laryngoscope. 2000;110(3 Pt 1):374–81.

    CAS  PubMed  Google Scholar 

  51. Kannan S, et al. Differential expression of cytokeratin proteins during tumour progression in oral mucosa. Epithelial Cell Biol. 1994;3(2):61–9.

    CAS  PubMed  Google Scholar 

  52. Kannan S, et al. Alterations in expression of terminal differentiation markers of keratinocytes during oral carcinogenesis. Pathobiology. 1994;62(3):127–33.

    CAS  PubMed  Google Scholar 

  53. Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Perez-Ordonez B, Gilbert R, Gullane P, Irish J, Kamel-Reid S. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Hum Mol Genet. 2009;18(24):4818–29.

    CAS  PubMed  Google Scholar 

  54. Yang CC, Hung PS, Wang PW, Liu CJ, Chu TH, Cheng HW, Lin SC. miR-181 as a putative biomarker for lymph-node metastasis of oral squamous cell carcinoma. J Oral Pathol Med. 2011;40(5):397–404.

    CAS  PubMed  Google Scholar 

  55. Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, Perez-Ordonez B, Jurisica I, O’Sullivan B, Waldron J, Gullane P, Cummings B, Liu FF. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 2010;16(4):1129–39.

    CAS  PubMed  Google Scholar 

  56. Abrahao AC, Bonelli BV, Nunes FD, Dias EP, Cabral MG. Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders. Braz Oral Res. 2011;25(1):34–41.

    PubMed  Google Scholar 

  57. Clague J, et al. Genetic variation in MicroRNA genes and risk of oral premalignant lesions. Mol Carcinog. 2010;49(2):183–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Chen HH, et al. Expression of human telomerase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan. Oral Oncol. 2007;43(2):122–9.

    CAS  PubMed  Google Scholar 

  59. Zhang L, Zhang W. Telomerase hTR and hTRT gene expression in oral precancerous lesions and squamous cell carcinomas. Chin J Dent Res. 1999;2(2):43–8.

    CAS  PubMed  Google Scholar 

  60. Kim HR, et al. Elevated expression of hTERT is associated with dysplastic cell transformation during human oral carcinogenesis in situ. Clin Cancer Res. 2001;7(10):3079–86.

    CAS  PubMed  Google Scholar 

  61. Liao J, et al. Telomerase activity in oral and maxillofacial tumors. Oral Oncol. 2000;36(4):347–52.

    CAS  PubMed  Google Scholar 

  62. Pannone G, et al. Prognostic value of human telomerase reverse transcriptase gene expression in oral carcinogenesis. Int J Oncol. 2007;30(6):1349–57.

    CAS  PubMed  Google Scholar 

  63. Routray S, Kheur SM, Kheur M. Osteopontin: a marker for invasive oral squamous cell carcinoma but not for potentially malignant epithelial dysplasias. Ann Diagn Pathol. 2013. pii: S1092-9134(13)00034-8. doi:10.1016/j.anndiagpath.2013.03.005. [Epub ahead of print].

  64. Pontes HA, Pontes FS, Fonseca FP, de Carvalho PL, Pereira EM, de Abreu MC, de Freitas Silva BS, dos Santos Pinto Jr D. Nuclear factor kappaB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma. Ann Diagn Pathol. 2013;17(1):45–50.

    PubMed  Google Scholar 

  65. Santhi WS, et al. NF-kappaB and COX-2 during oral tumorigenesis and in assessment of minimal residual disease in surgical margins. Exp Mol Pathol. 2006;81(2):123–30.

    CAS  PubMed  Google Scholar 

  66. Yarden Y, Schlessinger J. Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry. 1987;26(5):1443–51.

    CAS  PubMed  Google Scholar 

  67. Nishikawa R, et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci. 1994;91.

    Google Scholar 

  68. Taoudi Benchekroun M, et al. Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. Cancer Prev Res (Phila). 2010;3(7):800–9.

    Google Scholar 

  69. Lourenco SV, Coutinho-Camillo CM, Buim ME, Pereira CM, Carvalho AL, Kowalski LP, Soares FA. Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases. J Clin Pathol. 2010;63(7):609–14.

    PubMed  Google Scholar 

  70. Ries J, et al. Evaluation of MAGE-A expression and grade of dysplasia for predicting malignant progression of oral leukoplakia. Int J Oncol. 2012;41(3):1085–93.

    CAS  PubMed  Google Scholar 

  71. Nayyar AS, et al. Serum total protein, albumin and advanced oxidation protein products (AOPP)--implications in oral squamous cell carcinoma. Malays J Pathol. 2012;34(1):47–52.

    PubMed  Google Scholar 

  72. Arora S, et al. Stromelysin 3, Ets-1, and vascular endothelial growth factor expression in oral precancerous and cancerous lesions: correlation with microvessel density, progression, and prognosis. Clin Cancer Res. 2005;11(6):2272–84.

    CAS  PubMed  Google Scholar 

  73. Sudha VM, Hemavathy S. Role of bcl-2 oncoprotein in oral potentially malignant disorders and squamous cell carcinoma: an immunohistochemical study. Indian J Dent Res. 2011;22(4):520–5.

    CAS  PubMed  Google Scholar 

  74. Loro LL, Johannessen AC, Vintermyr OK. Decreased expression of bcl-2 in moderate and severe oral epithelia dysplasias. Oral Oncol. 2002;38(7):691–8.

    CAS  PubMed  Google Scholar 

  75. de Vicente JC, et al. Podoplanin expression in oral leukoplakia: tumorigenic role. Oral Oncol. 2013;49(6):598–603.

    PubMed  Google Scholar 

  76. Tripathi SC, et al. Nuclear S100A7 is associated with poor prognosis in head and neck cancer. PLoS One. 2010;5(8), e11939.

    PubMed  PubMed Central  Google Scholar 

  77. Dalerba P, Cho R, Clarke M. Cancer stem cells: models and concepts. Annu Rev Med. 2007;58:267–84.

    CAS  PubMed  Google Scholar 

  78. Prince M, Ailles L. Cancer stem cells in head and neck squamous cell cancer. J Clin Oncol. 2008;26(17):2871–5.

    PubMed  Google Scholar 

  79. Bhaijee F, et al. Cancer stem cells in head and neck squamous cell carcinoma: a review of current knowledge and future applications. Head Neck. 2012;34(6):894–9.

    PubMed  Google Scholar 

  80. Luo W, et al. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013;8(2), e56324.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Kim J, et al. Oct4-induced pluripotency in adult neural stem cells. Cell. 2009;136(3):411–9.

    CAS  PubMed  Google Scholar 

  82. Tai M-H, et al. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26(2):495–502.

    CAS  PubMed  Google Scholar 

  83. Hochedlinger K, et al. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell. 2005;121(3):465–77.

    CAS  PubMed  Google Scholar 

  84. Vigneswaran N, Beckers S, Waigel S, Mensah J, Wu J, Mo J, Fleisher KE, Bouquot J, Sacks PG, Zacharias W. Increased EMMPRIN (CD 147) expression during oral carcinogenesis. Exp Mol Pathol. 2006;80(2):147–59.

    CAS  PubMed  Google Scholar 

  85. Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, Chen DT, Tai LK, Yung MC, Chang SC, Ku HH, Chiou SH, Lo WL. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385(3):307–13.

    CAS  PubMed  Google Scholar 

  86. Abdulmajeed A, Dalley A, Farah C. Putative cancer stem cell marker expression in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med. 2013;42(10):755–60.

    CAS  PubMed  Google Scholar 

  87. Liu W, Wu L, Shen XM, Shi LJ, Zhang CP, Xu LQ, Zhou ZT. Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia. Int J Cancer. 2013;132(4):868–74.

    CAS  PubMed  Google Scholar 

  88. Ishiwata T, Matsuda Y, Naito Z. Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis. World J Gastroenterol. 2011;17(4):409–18.

    PubMed  PubMed Central  Google Scholar 

  89. Lim Y, et al. Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas. Oral Oncol. 2011;47(2):83–91.

    PubMed  Google Scholar 

  90. Günthert U, et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991;65(1):13–24.

    PubMed  Google Scholar 

  91. Kamarajan P, Shin JM, Qian X, Matte B, Zhu JY, Kapila YL. ADAM17-mediated CD44 cleavage promotes orasphere formation or stemness and tumorigenesis in HNSCC. Cancer Med. 2013;2(6):793–802.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Ravindran G, Devaraj H. Aberrant expression of CD133 and musashi-1 in preneoplastic and neoplastic human oral squamous epithelium and their correlation with clinicopathological factors. Head Neck. 2011;34(8):1129–35.

    PubMed  Google Scholar 

  93. Baeten J, et al. Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins. Transl Oncol. 2014;7(2):213–20.

    PubMed  PubMed Central  Google Scholar 

  94. Al-Tarawneh SK, et al. Defining salivary biomarkers using mass spectrometry-based proteomics: a systematic review. OMICS. 2011;15(6):353–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Brinkmann O, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population. Oral Oncol. 2011;47(1):51–5.

    CAS  PubMed  Google Scholar 

  96. Hu S, et al. Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res. 2008;14(19):6246–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Fountzilas G. Retinoids in the management of head and neck cancer. An update. J Chemother. 1994;6(2):127–38.

    CAS  PubMed  Google Scholar 

  98. Gorsky M, Epstein JB. The effect of retinoids on premalignant oral lesions: focus on topical therapy. Cancer. 2002;95(6):1258–64.

    CAS  PubMed  Google Scholar 

  99. Cheng AL, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895–900.

    CAS  PubMed  Google Scholar 

  100. Grandhi BK, et al. A novel combinatorial nanotechnology-based oral chemopreventive regimen demonstrates significant suppression of pancreatic cancer neoplastic lesions. Cancer Prev Res (Phila). 2013;6(10):1015–25.

    CAS  Google Scholar 

  101. Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007;255(2):170–81.

    CAS  PubMed  Google Scholar 

  102. Bianchini C, et al. Targeted therapy in head and neck cancer. Tumori. 2011;97(2):137–41.

    CAS  PubMed  Google Scholar 

  103. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11(1):9–22.

    CAS  PubMed  Google Scholar 

  104. Braakhuis BJ, et al. Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck. 2002;24(2):198–206.

    PubMed  Google Scholar 

  105. Feller LL, et al. Oral squamous cell carcinoma in relation to field precancerisation: pathobiology. Cancer Cell Int. 2013;13(1):31.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. van Oijen MG, Slootweg PJ. Oral field cancerization: carcinogen-induced independent events or micrometastatic deposits? Cancer Epidemiol Biomarkers Prev. 2000;9(3):249–56.

    PubMed  Google Scholar 

  107. Simon R, et al. Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells. Cancer Res. 2001;61(1):355–62.

    CAS  PubMed  Google Scholar 

  108. Izawa T, et al. Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas. Cancer. 2001;92(7):1807–17.

    CAS  PubMed  Google Scholar 

  109. Ogden GR, et al. Overexpression of p53 in normal oral mucosa of oral cancer patients does not necessarily predict further malignant disease. J Pathol. 1997;182(2):180–4.

    CAS  PubMed  Google Scholar 

  110. Lavieille JP, et al. p53 mutations and p53, Waf-1, Bax and Bcl-2 expression in field cancerization of the head and neck. Anticancer Res. 1998;18(6B):4741–9.

    CAS  PubMed  Google Scholar 

  111. Carey TE. Field cancerization: are multiple primary cancers monoclonal or polyclonal? Ann Med. 1996;28(3):183–8.

    CAS  PubMed  Google Scholar 

  112. Chu TY, et al. Monoclonality and surface lesion-specific microsatellite alterations in premalignant and malignant neoplasia of uterine cervix: a local field effect of genomic instability and clonal evolution. Genes Chromosomes Cancer. 1999;24(2):127–34.

    CAS  PubMed  Google Scholar 

  113. Angadi PV, et al. Oral field cancerization: current evidence and future perspectives. Oral Maxillofac Surg. 2012;16(2):171–80.

    PubMed  Google Scholar 

  114. Forsti A, et al. Loss of heterozygosity in tumour-adjacent normal tissue of breast and bladder cancer. Eur J Cancer. 2001;37(11):1372–80.

    CAS  PubMed  Google Scholar 

  115. Mao L, et al. Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues. Cancer Res. 1996;56(24):5600–4.

    CAS  PubMed  Google Scholar 

  116. Braakhuis BJ, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63(8):1727–30.

    CAS  PubMed  Google Scholar 

  117. Galipeau PC, et al. Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett’s) tissue. J Natl Cancer Inst. 1999;91(24):2087–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Lindenbergh-van der Plas M, et al. Prognostic significance of truncating TP53 mutations in head and neck squamous cell carcinoma. Clin Cancer Res. 2011;17(11):3733–41.

    CAS  PubMed  Google Scholar 

  119. Bongers V, Snow GB, Braakhuis BJ. The role of glutathione S-transferases in head and neck squamous cell carcinogenesis. Eur J Cancer B Oral Oncol. 1995;31B(6):349–54.

    CAS  PubMed  Google Scholar 

  120. Blons H, Laurent-Puig P. TP53 and head and neck neoplasms. Hum Mutat. 2003;21(3):252–7.

    CAS  PubMed  Google Scholar 

  121. Tunca B, et al. P53 gene mutations in surgical margins and primary tumor tissues of patients with squamous cell carcinoma of the head and neck. Tumori. 2007;93(2):182–8.

    PubMed  Google Scholar 

  122. van Houten VM, et al. Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study. Clin Cancer Res. 2004;10(11):3614–20.

    PubMed  Google Scholar 

  123. Tabor MP, et al. Genetically altered fields as origin of locally recurrent head and neck cancer: a retrospective study. Clin Cancer Res. 2004;10(11):3607–13.

    CAS  PubMed  Google Scholar 

  124. Braakhuis BJ, Leemans CR, Brakenhoff RH. Correspondence re: M. P. Rosin et al., 3p14 and 9p21 Loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites. Cancer Res. 2002;62:6447–50. Cancer Res. 2003;63(16):5167–8; author reply 5168–9.

    Google Scholar 

  125. van der Toorn PP, et al. Mapping of resection margins of oral cancer for p53 overexpression and chromosome instability to detect residual (pre)malignant cells. J Pathol. 2001;193(1):66–72.

    PubMed  Google Scholar 

  126. Lydiatt WM, et al. Molecular support for field cancerization in the head and neck. Cancer. 1998;82(7):1376–80.

    CAS  PubMed  Google Scholar 

  127. Jang SJ, et al. Multiple oral squamous epithelial lesions: are they genetically related? Oncogene. 2001;20(18):2235–42.

    CAS  PubMed  Google Scholar 

  128. Patel MM, et al. Evaluation of telomerase activation in head and neck cancer. Oral Oncol. 1999;35(5):510–5.

    CAS  PubMed  Google Scholar 

  129. Ries JC, et al. Correlation of telomerase activity, clinical prognosis and therapy in oral carcinogenesis. Anticancer Res. 2001;21(2A):1057–63.

    CAS  PubMed  Google Scholar 

  130. Raimondi A, Cabrini R, Itoiz ME. Ploidy analysis of field cancerization and cancer development in the hamster cheek pouch carcinogenesis model. J Oral Pathol Med. 2005;34(4):227–31.

    CAS  PubMed  Google Scholar 

  131. Monti-Hughes A, et al. The hamster cheek pouch model for field cancerization studies. Periodontology. 2015;67(1):292–311.

    Google Scholar 

  132. Kim J, et al. Chromosome polysomy and histological characteristics in oral premalignant lesions. Cancer Epidemiol Biomarkers Prev. 2001;10(4):319–25.

    CAS  PubMed  Google Scholar 

  133. Giaretti W, et al. Chromosomal instability, DNA index, dysplasia, and subsite in oral premalignancy as intermediate endpoints of risk of cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(6):1133–41.

    CAS  PubMed  Google Scholar 

  134. Giaretti W, et al. Chromosomal instability, aneuploidy and routine high-resolution DNA content analysis in oral cancer risk evaluation. Future Oncol. 2012;8(10):1257–71.

    CAS  PubMed  Google Scholar 

  135. Giaretti W, et al. Genomic aberrations in normal appearing mucosa fields distal from oral potentially malignant lesions. Cell Oncol (Dordr). 2012;35(1):43–52.

    CAS  Google Scholar 

  136. Pentenero M, et al. Field effect in oral precancer as assessed by DNA flow cytometry and array-CGH. J Oral Pathol Med. 2012;41(2):119–23.

    CAS  PubMed  Google Scholar 

  137. Choi G, Chung K. Polysomies of chromosomes 7 and 17 in head and neck squamous cell carcinomas. Arch Otolaryngol Head Neck Surg. 1996;122(10):1062–7.

    CAS  PubMed  Google Scholar 

  138. Voravud N, et al. Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res. 1993;53(12):2874–83.

    CAS  PubMed  Google Scholar 

  139. Lopez-Blanc SA, et al. Nucleolar organizer regions (AgNOR) and subepithelial vascularization as field cancerization markers in oral mucosa biopsies of alcoholic and smoking patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(5):747–53.

    PubMed  Google Scholar 

  140. Jin Y, et al. A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium. Virchows Arch. 1995;427(2):145–51.

    CAS  PubMed  Google Scholar 

  141. Kale AD, et al. Establishment of field change by expression of cytokeratins 8/18, 19, and MMP-9 in an apparently normal oral mucosa adjacent to squamous cell carcinoma: A immunohistochemical study. J Oral Maxillofac Pathol. 2012;16(1):10–5.

    PubMed  PubMed Central  Google Scholar 

  142. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res. 1993;53(15):3579–84.

    CAS  PubMed  Google Scholar 

  143. Bloching MM, et al. Tumor risk assessment by means of immunocytochemical detection of early pre-malignant changes in buccal smears. Oncol Rep. 2008;19(6):1373–9.

    PubMed  Google Scholar 

  144. Bankfalvi A, et al. Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression. J Pathol. 2002;198(3):343–51.

    CAS  PubMed  Google Scholar 

  145. Squier C, Brogden K. Human oral mucosa: development, structure and function. Hoboken Wiley-Blackwell; 2011. p. 176.

    Google Scholar 

  146. Suresh A, et al. Resistance/response molecular signature for oral tongue squamous cell carcinoma. Dis Markers. 2012;32(1):51–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Mohanta S, Trivedi N, Das D, Hicks Jr W, Gupta V, Suresh A, Kuriakose MA. Tumor initiating cells as indicators as marker of local recurrence in head and neck squamous cell carcinoma. In: 8th international conference on head and neck cancer. A.H.N. Society, Editor. 2012. JAMA Otolaryngology– Head and Neck Surgery. Toronto.

    Google Scholar 

  148. Qiao B, et al. The expression profile of Oct4 and Sox2 in the carcinogenesis of oral mucosa. Int J Clin Exp Pathol. 2014;7(1):28–37.

    PubMed  Google Scholar 

  149. McDonald SA, et al. Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Gastroenterology. 2008;134(2):500–10.

    CAS  PubMed  Google Scholar 

  150. Garcia SB, et al. Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets. J Pathol. 1999;187(1):61–81.

    CAS  PubMed  Google Scholar 

  151. Trujillo KA, et al. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer. 2011;129(6):1310–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Hiraga T, Ito S, Nakamura H. Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res. 2013;73(13):4112–22.

    CAS  PubMed  Google Scholar 

  153. Giordano A, et al. Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients. Ann Oncol. 2013;24(10):2515–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Mohanta S, Suresh A, Das D, Kuriakose MA. Cancer stem cells and field cancerization of oral squamous cell carcinoma. Oral Oncol.2015;51(7)643–51.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Integrated Head and Neck Oncology Program, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India

    Amritha Suresh PhD, Simple Mohanta PhD & Gangotri Siddappa PhD

  2. Department of Head and Neck, Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA

    Moni Abraham Kuriakose MD, FRCS

Authors
  1. Amritha Suresh PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moni Abraham Kuriakose MD, FRCS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simple Mohanta PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gangotri Siddappa PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Head and Neck, Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, USA

    Moni Abraham Kuriakose

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Suresh, A., Kuriakose, M.A., Mohanta, S., Siddappa, G. (2017). Carcinogenesis and Field Cancerization in Oral Squamous Cell Carcinoma. In: Kuriakose, M.A. (eds) Contemporary Oral Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-14911-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-14911-0_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-14910-3

  • Online ISBN: 978-3-319-14911-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation