Skip to main content

Advertisement

SpringerLink
Log in

Oral field cancerization: current evidence and future perspectives

  • Review Article
  • Published:
Oral and Maxillofacial Surgery Aims and scope Submit manuscript

Abstract

Introduction

Oral field cancerization implies that oral cancer does not arise as an isolated cellular phenomenon but rather as an anaplastic tendency involving many cells at once and results in the multifocal development of cancer at various rates within the entire field in response to a carcinogen especially tobacco. This concept has been frequently used to explain the occurrence of multiple primary cancers and recurrences following complete excision of oral cancer.

Discussion

This review deals in detail with the origin, principle, various theories used to explain this effect and molecular, genetic, as well as cytogenetic findings related to oral field cancerization. Further, the clinical implications and future research directives are also discussed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium: clinical implication of multicentric origin. Cancer 6:963–968

    Article  PubMed  CAS  Google Scholar 

  2. Slaughter DP (1944) The multiplicity of origin of malignant tumors: collective review. Internat Abstr Surg 79:89–98

    Google Scholar 

  3. Slaughter DP (1946) Multicentric origin of intraoral carcinoma. Surgery 20:133–135

    PubMed  CAS  Google Scholar 

  4. Boudewijn JM, Braakhuis T, Tabor MT, Kumar JA, Leemans R, Barkenhoff RH et al (2003) A genetic explanation of slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 63:1727–1730

    Google Scholar 

  5. Ogden GR, Cowpe JG, Green MW (1990) Evidence of field change in oral cancer. Br J Oral Maxillofac Surg 28:390–392

    Article  PubMed  CAS  Google Scholar 

  6. Gabriel DD, Jakupciak PJ, Machin M, Parr R (2007) Clinical implications and utility of field cancerization. Cancer Cell Int 7:2

    Article  Google Scholar 

  7. Monique G, Oijen V, Slootweg PJ (2000) Oral field cancerization: carcinogen-induced independent events or micrometastic deposits? Cancer Epidemiol Biomarkers Prev 9:249–256

    Google Scholar 

  8. van Houten VM, Leemans CR, Kummer JA, Dijkstra J, Kuik DJ, van den Brekel MW, Snow GB, Brakenhoff RH (2004) Molecular diagnosis of surgical margins and local recurrence in head and cancer patients: a prospective study. Clin Cancer Res 10:3614–3620

    Article  PubMed  Google Scholar 

  9. Califano J, Van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S et al (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:2488–2492

    PubMed  CAS  Google Scholar 

  10. Bedi GC, Westra WH, Gabrielson E, Koch W, Sidransky D (1996) Multiple head and neck tumors: evidence for common clonal origin. Cancer Res 56:2484–2487

    PubMed  CAS  Google Scholar 

  11. Partridge M, Emilion G, Pateromichelakis S, Philips E, Langdon (1997) Field cancerization of oral cavity: comparison of the spectrum of molecular alterations in cases presenting with both dysplastic and malignant lesions. Oral Oncol 33:332–337

    Article  PubMed  CAS  Google Scholar 

  12. Day G, Blot WJ, Shore RE, McLaughlin JK, Austin DF, Greenberg RS (1994) Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86:131–137

    Article  PubMed  CAS  Google Scholar 

  13. Cianfriglia F, Di Gregorio DA, Manieri A (1999) Multiple primary tumors in patients with oral squamous cell carcinoma. Oral Oncol 35:157–163

    Article  PubMed  CAS  Google Scholar 

  14. Prevo LJ, Sanchez CA, Galipeau PC, Reid BJ (1999) p53-mutant clones and field effects in Barrett’s esophagus. Cancer Res 59:4784–4787

    PubMed  CAS  Google Scholar 

  15. Jang SJ, Chiba I, Hirai A, Hong WK, Mao L (2001) Multiple oral squamous epithelial lesions: are they genetically related? Oncogene 20:2235–2242

    Article  PubMed  CAS  Google Scholar 

  16. Tabor MP, Brakenhoff RH, Rujiter-Schippers HJ, van der Wal JE, Snow GB, Leemans CR, Braakhuis BJ (2002) Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 161:1051–1060

    Article  PubMed  CAS  Google Scholar 

  17. Simon R, Eltze E, Schäfer KL, Bürger H, Semjonow A, Hertle L, Dockhorn-Dworniczak B, Terpe HJ, Böcker W (2001) Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells. Cancer Res 61:355–362

    PubMed  CAS  Google Scholar 

  18. Braakhuis BJ, Tabor MP, Leemans CR (2002) Second primary tumors and field cancerization in oral and or pharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24:198–206

    Article  PubMed  Google Scholar 

  19. Boudewijin JM, Braakhuis BJ, Leemans CR, Brakenhoff RH (2004) A genetic progression model of oral cancer: current evidence and clinical implications. J Oral Pathol Med 33:317–322

    Article  Google Scholar 

  20. Wright A, Shear M (1985) Epithelial dysplasia immediately adjacent to oral squamous cell carcinomas. J Oral Pathol 14:559–564

    Article  PubMed  CAS  Google Scholar 

  21. Kannan S, Kartha P, Balaram G, Jagadeesh C, Radhakrishna P, Pillai R (1996) Ultrastructural analysis of the adjacent epithelium of oral squamous cell carcinoma. Br J Oral Maxillofac Surg 34:51–57

    Article  PubMed  CAS  Google Scholar 

  22. Thomson PJ (2002) Field change and oral cancer: new evidence for widespread carcinogenesis? Int J Oral Maxillofac Surg 31:262–266

    Article  PubMed  CAS  Google Scholar 

  23. Incze J, Vaughan CW, Lui P, Strong MS, Kulapaditharom B (1982) Premalignant changes in normal appearing epithelium in patients with squamous cell carcinoma of the upper areodigestive tract. Am J Surg 144:401–402

    Article  PubMed  CAS  Google Scholar 

  24. Nieburgs HE, Herman BE, Reisman H (1962) Buccal cell changes in patients with malignant tumors. Lab Invest 11:80–88

    Google Scholar 

  25. Cowpe JG, Longmore RB, Green MW (1988) Quantitative exfoliative cytology of normal oral mucosal smears. J Royal Society Med 81:509–511

    CAS  Google Scholar 

  26. Castigliano SC (1968) Influence of continuous smoking on the incidence of second primary cancers involving mouth, pharynx and larynx. JADA 77:580

    PubMed  CAS  Google Scholar 

  27. Wynder EI, Dodo H, Block DA, Grant RC, Moore OS (1969) Epidemiology investigation of multiple cancers in the upper alimentary and respiratory tracts. Cancer 24:730–739

    Article  PubMed  CAS  Google Scholar 

  28. Copper MP, Braakhuis BJ, de Vries N, van Dongen GA, Nauta JJ, Snow GB (1993) A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as a potential immediate endpoints in chemoprevention trials. Cancer 71:825–830

    Article  PubMed  CAS  Google Scholar 

  29. Ogden GR, Lane EB, Hopwood DV, Chisholm DM (1993) Evidence of field change in oral cancer based on cytokeratin expression. Br J Oral Maxillofac Surg 67:1324–1330

    CAS  Google Scholar 

  30. Bongers V, Snow GB, de Vries N, Braakhuis BJ (1996) Potential early markers of carcinogenesis in the mucosa of the head and neck using exfoliative cytology. J Pathol 178:284–289

    Article  PubMed  CAS  Google Scholar 

  31. Bosch FX, Ouhayoun JP, Bader BL, Collin C, Grund C, Lee I, Franke WW (1989) Extensive changes in cytokeratin expression patterns in pathologically affected human gingiva. Virchows Arch B Cell Pathol 58:59–77

    Article  CAS  Google Scholar 

  32. Bartkova J, Lukas J, Muller H, Strauss M, Gusterson B, Bartek J (1995) Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res 55:949–956

    PubMed  CAS  Google Scholar 

  33. Bloching M, Soulsby H, Naumann A, Aust W, Merkel D, Braun T, Naim R (2008) Tumor risk assessment by means of immunocytochemical detection of premalignant chages in buccal smears. Oncol Rep 19:1373–1379

    PubMed  Google Scholar 

  34. Eisbruch A, Blick M, Lee JS, Sacks PG, Gutterman J (1987) Analysis of the epidermal growth factor receptor gene in fresh human head and neck tumors. Cancer Res 47:3603–3605

    PubMed  CAS  Google Scholar 

  35. Grandis JR, Tweardy DJ (1993) 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 53:3579–3584

    PubMed  CAS  Google Scholar 

  36. Christensen ME, Engbaek F, Therkildsen MH, Bretlau P, Nexo A (1995) A sensitive enzyme-linked immunosorbent assay used for quantitation of epidermal growth factor receptor protein in head and neck carcinomas: evaluation, interpretations and limitations. Br J Cancer 72:1487–1493

    Article  PubMed  CAS  Google Scholar 

  37. Shin DM, Ro JY, Hong WK, Hittelman WN (1994) Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 54:3153–3159

    PubMed  CAS  Google Scholar 

  38. Van Oijen MGCT, Rijksen G, Tenbroek FW, Slootweg PJ (1998) Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse. Oral Dis 4:4–8

    Article  PubMed  Google Scholar 

  39. Bergle W, Bier H, Ganzer U (1989) The expression of epidermal growth factor receptors in the oral mucosa of patients with oral cancer. Arch Oto rhino laryngol 246:121–125

    Article  Google Scholar 

  40. Werkmeister R, Brandt B, Joos U (1996) The erbB oncogenes as prognostic markers on oral squamous cell carcinomas. Am J Surg 172:681–683

    Article  PubMed  CAS  Google Scholar 

  41. Szymańska K, Levi JE, Menezes A, Wünsch-Filho V, Eluf-Neto J, Koifman S et al (2010) TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America. Carcinogenesis 31:1054–1059

    Article  PubMed  Google Scholar 

  42. Shin DM, Ro JY, Hong WK, Hittelman WN (1993) Sequential increase in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker. J Natl Cancer Inst 12:971–978

    Google Scholar 

  43. Schwindt AE, Savino TM, Lanfranchi HE, Marschoff E, Cabrini RL, Itoiz ME (1994) Nuclear organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa. Cancer 73:2674–2679

    Article  Google Scholar 

  44. van Oijen MG, Gilsing MM, Rijksen G, Hordijk GJ, Slootweg PJ (1998) Increased number of proliferating cells in oral epithelium from smokers and ex-smokers. Oral Oncol 16:3158–3168

    Google Scholar 

  45. Lopez-Blanc SA, Collet AM, Gandolfo MS, Femopase F, Hernandez SL, Tomasi VH, Paparella ML, Itoiz ME (2009) 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 108:747–753

    Article  PubMed  Google Scholar 

  46. Bloching M, Hoffman A, Lauteschalager C, Berghaus A, Grummt T (2000) Exfoliative cytology of normal buccal mucosa to predict the relative risk of cancer in the upper aerodigestive tract using the MN-assay. Oral Oncol 36:550–555

    Article  PubMed  CAS  Google Scholar 

  47. Bloching M, Hoffman A, Berghaus A, Lauteschalager C, Grummt T (2000) Micronuclei as biological markers for the detection of local cancer transformation in the upper aerodigestive tract. HNO 48:444–450

    Article  PubMed  CAS  Google Scholar 

  48. Birchall MA, Schock E, Harmon BV, Gobé G (1997) Apoptosis, mitosis, PCNA and bcl-2 in normal, leukoplakia and malignant epithelia of the human oral cavity: prospective, in vivo study. Oral Oncol 33:419–425

    Article  PubMed  CAS  Google Scholar 

  49. Bongers V, Snow GB, de Vries N, Cattan AR, Hall AG, van der Waal I, Braakhuis BJ (1995) Second primary head and neck squamous cell carcinoma predicted by the glutathione S-transferase expression in healthy tissue in the direct vicinity of the first tumor. Lab Invest 73:503–510

    PubMed  CAS  Google Scholar 

  50. El-Gazzar R, Macluskey M, Ogden GR (2005) Evidence for a field change effect based on angiogenesis in the oral mucosa? A brief report. Oral Oncol 41:25–30

    Article  PubMed  CAS  Google Scholar 

  51. el-Naggar AK, Lai S, Luna MA, Zhou XD, Weber RS, Goepfert H, Batsakis JG (1995) Sequential p53 mutation analysis of the preinvasive and invasive head and squamous carcinoma. Int J Cancer 64:196–20

    Article  PubMed  CAS  Google Scholar 

  52. Shin DM, Kim J, Ro JY, Hittelman J, Roth JA, Hong WK, Hittelman WN (1994) Activation of p53 expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 54:321–326

    PubMed  CAS  Google Scholar 

  53. van Oijen MGCT, van de Craats JG, Slootweg PJ (1999) p53 overexpression in oral mucosa in relation to smoking. J Pathol 187:469–474

    Article  PubMed  Google Scholar 

  54. Ness M, Homann N, Discher H, Andl T, Enders C, Herold-Mende C, Schuhmann A, Bosch FX (1993) Expression of p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors. Cancer Res 53:4189–4196

    Google Scholar 

  55. Laveille JP, Brambilla E, Lavieille R (1995) Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck. Acta Otolaryngol 115:334–339

    Article  Google Scholar 

  56. Cruz IB, Snijders PJ, Meijer CJ, Braakhuis BJ, Snow GB, Walboomers JM, van der Waal I (1998) 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 184:360–368

    Article  PubMed  CAS  Google Scholar 

  57. Waridel F, Estreicher A, Bron L, Flaman JM, Fontolliet C, Monnier P, Frebourg T, Iggo R (1997) Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract. Oncogene 14:163–169

    Article  PubMed  CAS  Google Scholar 

  58. Nakanishi Y, Noguchi M, Matsuno Y, Saikawa M, Mukai K, Shimosato Y, Hirohashi S (1995) p53 expression in multicentric squamous cell carcinoma and surrounding squamous epithelium of the aerodigestive tract. Cancer 75:1657–1662

    Article  PubMed  CAS  Google Scholar 

  59. Ogden GR, Chisholm DM, Morris AM, Stevenson JH (1997) Overexpression of p53 in normal mucosa of oral cancer patients does not necessarily predict further malignant disease. J Pathol 182:180–184

    Article  PubMed  CAS  Google Scholar 

  60. Ha PK, Califano JA (2003) The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14(5):363–369

    Article  PubMed  Google Scholar 

  61. Weinberg WC, Howard JC, Iannaconne PM (1985) Histological demonstration of mosaicism in a series of chimeric rats produced between congenic strains. Science 227:524–527

    Article  PubMed  CAS  Google Scholar 

  62. Wengler GS, Allen RC, Parolini O, Smith H, Conley ME (1993) Nonrandom X chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency. J Immunol 150:700–704

    PubMed  CAS  Google Scholar 

  63. Worsham MJ, Wolman SR, Carey TE, Zarbo RJ, Benninger MS, Van Dyke DL (1995) Common clonal origin of synchronous primary head and neck squamous cell carcinomas: analysis by tumor karyotypes and fluorescence in situ hybridization. Human Pathol 26:251–261

    Article  CAS  Google Scholar 

  64. van Oijen MG, Leppers VD, Straat FG, Tilanus MG, Slootweg PJ (2000) The origin of multiple squamous cell carcinomas in the aerodigestive tract. Cancer 88:884–893

    Article  PubMed  Google Scholar 

  65. Partridge M, Pateromichelakis S, Phillips E, Emilion GG, A'Hern RP, Langdon JD (2000) 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 Res 60:3893–3898

    PubMed  CAS  Google Scholar 

  66. Tabor MP, Brakenhoff RH, van Houten VM, Kummer JA, Snel MH, Snijders PJ et al (2001) Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7:1523–1532

    PubMed  CAS  Google Scholar 

  67. Ha PK, Tong BC, Westra WH, Sanchez-Cespedes M, Parrella P, Zahurak M, Sidransky D, Califano JA (2002) Mitochondrial C-tract alteration in premalignant lesions of the head and neck: a marker for progression and clonal proliferation. Clin Cancer Res 8:2260–2265

    PubMed  CAS  Google Scholar 

  68. Hittelman WN, Kim HJ, Lee JS, Shin DM, Lippman SM, Kim J, Ro JY, Hong WK (1996) Detection of instability of tissue fields at risk: in situ hybridization. J Cell Biochem Suppl 25:57–62

    Article  PubMed  CAS  Google Scholar 

  69. Ai H, Barrera J, Pan Z, Meyers AD, Varella-Garcia M (1999) Identification of individuals at high risk for head and neck carcinogenesis using chromosome aneuploidy detected by fluorescence in situ hybridization. Mutat Res 439:223–232

    PubMed  CAS  Google Scholar 

  70. Voravud N, Shin DM, Ro JY, Lee JS, Hong WK, Hittelman WN (1993) Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res 53:2874–2883

    PubMed  CAS  Google Scholar 

  71. Lee N, Ye Y, Li X, Schweitzer C, Nisen P (1994) Allelic loss on chromosome 13 can precede histological changes in head and neck cancer. Int J Oncol 5:205–210

    PubMed  CAS  Google Scholar 

  72. Leeman CR (2007) Status of primary tumor surgical margins in squamous head and neck cancer: prognostic implications. Curr Opin Otolaryngol Head Neck Surg 15:74–81

    Article  Google Scholar 

  73. Thomson PJ, Hamadah O (2007) Cancerisation within the oral cavity: the use of ‘field mapping biopsies’ in clinical management. Oral Oncol 43:20–26

    Article  PubMed  CAS  Google Scholar 

  74. Papadimitrakopoulou VA, Shin DM, Hong WK (1996) Molecular and cellular biomarkers for field cancerization and multistep process in head and neck tumorigenesis 15:53–76

  75. Lee JS, Lippman SM, Hong WK, Ro JY, Kim SY, Lotan R, Hittelman WN (1992) Determination of biomarkers for intermediate end points in chemoprevention trials. Cancer Res 52:2707s–2710s

    PubMed  CAS  Google Scholar 

  76. Benner SE, Hong WK, Lippman SM, Lee JS, Hittelman WM (1992) Intermediate biomarkers in upper aerodigestive tract and lung chemoprevention trials. J Cell Biochem Suppl 16G:33–38

    Article  PubMed  CAS  Google Scholar 

  77. Smith W, Saba N (2005) Retinoids as chemoprevention for head and neck cancer: where do we go from here? Crit Rev Oncol Hematol 55:143–152

    Article  PubMed  Google Scholar 

  78. Lippman SM, Hawk ET (2009) Cancer prevention: from 1727 to milestones of the past 100 years. Cancer Res 69:5269–5284

    Article  PubMed  CAS  Google Scholar 

  79. Voravud N (1996) Chemoprevention of head and neck cancer. J Med Assoc Thai 79:185–193

    PubMed  CAS  Google Scholar 

  80. Höckel M, Dornhöfer N (2005) The hydra phenomenon of cancer: why tumors recur locally after microscopically complete resection. Cancer Res 65:2997–3002

    PubMed  Google Scholar 

  81. Ge L, Meng W, Zhou H, Bhowmick N (2010) Could stroma contribute to field cancerization? Med Hypotheses 75(1):26–31

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. KLE VK Institute of Dental Sciences and Hospital, Belgaum, 590010, Karnataka, India

    Punnya V. Angadi & Sanjay S. Rao

  2. Raja Rajeshwari Dental College, Bangalore, Karnataka, India

    J. K. Savitha

  3. Mamata Dental College, Khammam, Andhra Pradesh, India

    Y. Sivaranjini

Authors
  1. Punnya V. Angadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. K. Savitha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjay S. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Sivaranjini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Punnya V. Angadi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Angadi, P.V., Savitha, J.K., Rao, S.S. et al. Oral field cancerization: current evidence and future perspectives. Oral Maxillofac Surg 16, 171–180 (2012). https://doi.org/10.1007/s10006-012-0317-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10006-012-0317-x

Keywords

Search

Navigation