Chemoprevention in Head and Neck Cancer

  • Ann Mellott
  • Everett Vokes
Part of the Cancer Treatment and Research book series (CTAR, volume 106)


Approximately 40,000 new cases of squamous cell carcinomas of the head and neck are diagnosed each year in the United States1. These oral, pharyngeal, laryngeal and sinus cancers represent about 5% of total cancer incidence. The majority of these patients present with disease confined to the head and neck region, with distant metastases occurring in less then 5% of patients at diagnosis. Traditionally surgery and radiation have been the modalities used to treat these cancers. Though the majority of AJC stage I and stageIIpatients may be cured with surgery and/or radiation therapy, less then 40% of patients with AJC stageIIIand IV are cured with this approach. More recently, clinical trials studying the combined approach of chemotherapy and radiation have reported 3-year survival rates in excess of 50%.2As the long-term prognosis of these advanced stage patients improves, and combination therapies become more standard, these patients are faced with significant risk of other cancers.


Neck Cancer Cancer Chemoprevention Field Cancerization Oral Leukoplakia Betel Quid 
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.


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  1. 1.
    Greenlee Robert, Murray T, Bolden S, Wingo, P. Cancer Statistics, 2000. Ca Cancer J Clinics, 2000; 50:7–33.CrossRefGoogle Scholar
  2. 2.
    Kies MS, Haraf DJ, Athanasiadis I, Kozloff M, Mittal B, Pelzer H, Rademaker AW, Wenig B, Weichselbaum RR, Vokes EE. Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: improved disease control and survival. J Clin. Onco. 1998; 16(8) 2751–2721.Google Scholar
  3. 3.
    Shin et al. ASCO 2000, 1632.Google Scholar
  4. 4.
    Hong WK, Lippman SC, Itri L, Karp, Lee JS, Byers R et al. Prevention of second primary tumors with isotretinoin in squamous cell carcinoma of the head and neck. N. Eng J Med, 1990;323:795–801.CrossRefGoogle Scholar
  5. 5.
    Decker J, Goldstein JC,. Risk factors in head and neck cacner. N. Engl. J Med 1982, 306:1151–5.Google Scholar
  6. 6.
    Jacobs CD,. Etiologic consideration for head and neck squamous cancers. In: Jacobs C, ed. Carcinomas of the head and neck: evaluation and management. Boston: Kluwer Academic, 1990;265–82.CrossRefGoogle Scholar
  7. 7.
    Winn DM, Blot WJ, McLaughlin JK, et al. Mouth wash use and toral conditions in the risk of oral and pharyngeal cancer. Cancer Res 1991;51:3044–7.PubMedGoogle Scholar
  8. 8.
    Falk RT, Pickle LW, Brown LM, Mason TJ, Buffier PA, Fraumeni JF Jr. Effect of smoking and alochol consumption on laryngeal cancer risk in coastal Texas. Cancer Res 1989;49:4024–9.PubMedGoogle Scholar
  9. 9.
    Pierce JP, Riore MC, Novotny TE et al. Trends in cigarette smoking in the United States, Projections to 2000. JAMA, 1989; 26(1)61–5.CrossRefGoogle Scholar
  10. 10.
    Greenlee Robert, Murray T, Bolden S, Wingo, P. Cancer Statistics, 2000. Ca Cancer J Clinics, 2000; 50:7–33.CrossRefGoogle Scholar
  11. 11.
    Coleman WB, Tsonglias GJ. Multiple mechanisms acclount for genomic instability and molecular mutation in neoplastic transformation. Clin Chem, 1995, 41:644–657.PubMedGoogle Scholar
  12. 12.
    Wright, N, Alison M. Cell proliferation during carcinogenesis in squamous epithelium. In: The Biology of Epithelial Cell Populations, 2 vol. Oxford: Clarendon Press, 1984, vol 1: pp 421–444.Google Scholar
  13. 13.
    Slaughter DP, Southwick HW and Smejkai W. Field cancerization in oral stratified squamous epithleium“ clinical implications of multicentric origin. Cancer (Phila), 1953; 6:963–968.CrossRefGoogle Scholar
  14. 14.
    Somers KD, Merrick MA, Lopez, ME, Incognito LS, Schecter GL and Casey, G Frequent p53 mutations in head and neck cancer, Cancer Res. 1992; 52:5997–6000.PubMedGoogle Scholar
  15. 15.
    Chun, KY, Mukhopadhyay, T Kim J, Casson A, Ro JY, Geopfert H and Hong WK. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res. 1993; 53:1676–1683.Google Scholar
  16. 16.
    Westra et al. Second Esophageal Tumors in Patients with head and neck squamousc ell carcinoma: an assesment of Clonal Relationships, Clinical Cancer Research, 1999; 5:1862–1867.PubMedGoogle Scholar
  17. 17.
    Renan MJ. How many mutations are required for tumorigenesis? Implications from human cancer data. Mo. Carcinog. 1993, 138–146.Google Scholar
  18. 18.
    Fearon ER and Vogelstein BA. A genetic model for colorectal tumorigenesis.Cell, 1990:6:759–767.CrossRefGoogle Scholar
  19. 19.
    Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Presinger AC, Lepport M et al. Genetic alterations during colorectal tumor development. N Engl J Med. 1988: 319:525–532.PubMedCrossRefGoogle Scholar
  20. 20.
    Simoneau AR, Jones PA. Bladder Cancer: the molecular progression to invasive disease. World J. Urol, 1994, 12:89–95.Google Scholar
  21. 21.
    Decker J, Goldstein JC. Risk factors in head and neck cancer. N Engl J Med 1982;3–6:3–6.CrossRefGoogle Scholar
  22. 22.
    Jacobs CD, Etiologic considerations for head and neck squamous cancers. In: Jacobs C ed. Carcinomas of the head and neck: evaluation and management. Boston: Kluwer Academic, 1990:265–82.CrossRefGoogle Scholar
  23. 23.
    Silverman S Jr, ed. Oral cancer 3rded. Atlanta: American Cancer Society, 1990.Google Scholar
  24. 24.
    Kramer, IR, Lucas RB, Pindborg JJ, Sobin LH, Definition of leukoplakia and related lesions; an aid to studies on oral precancer. Oral Surg 1978;46:518–39.PubMedCrossRefGoogle Scholar
  25. 25.
    Silverman S Jr., Gorsky M, Lozada F. Oral leukoplakia and malignant transformation: A follow-up study of 257 patients. Cancer 53:563–568, 1984.PubMedCrossRefGoogle Scholar
  26. 26.
    Califano et al. Genetic progression model for head and neck cancer: Implications for field cancerization“, Cancer Research, 1996; 56:2488–2492.PubMedGoogle Scholar
  27. 27.
    Califano J, Van der Riet P, Clayman G, et al. A genetic progression model for head and neck cancer; implications for field cancerization. Cancer Res, 1996; 56:2458–2492.Google Scholar
  28. 28.
    Carey TE, Van Dyke DL, Worsham MJ. Nonrandom chromosome aberrations & clinical populations in head and neck cancer. Anticancer Res. 1993; 13:2561.Google Scholar
  29. 29.
    Jin Y, Mertens F, Mandahl N et al. Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas; influence of culture conditions of karotypic pattern. Cancer Res. 1993;53:2140.Google Scholar
  30. 30.
    Van Dyke DL, Worsham MJ, Benninger MS et al. Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region. Gene chromosomes Cancer, 1994; 9:192–206.CrossRefGoogle Scholar
  31. 31.
    Chromosome changes characterizing in vitro response to radiation in human squamous cell carcinoma lines..Cancer Res. 1993:53:5542.Google Scholar
  32. 32.
    Voravud N, Shin DM Ro JY, Lee JS, Hong WK Hittelman WN. Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorogenesis. Cancer Res. 1993:53:2874.PubMedGoogle Scholar
  33. 33.
    Lotan R, Xu XC, Lippman SM et al. Suppression of retinoic acid receptor beta in premalignant oral lesions and its upregulation by isoretinoin. N Engl J. Med 1995, 1405–1410.Google Scholar
  34. 34.
    Zhou DJ, Casey G, Cline MJ. Amplification of human int-2 in breast cancers and squamous carcinomas. Oncogene 1988;2:279–282.PubMedGoogle Scholar
  35. 35.
    Somers KD, Cartwright SL, Schecter Gl. Amplification of int-2 gene in human head and neck squamous cell carcinomas. Oncogene 1988; 2:279–82.Google Scholar
  36. 36.
    Merritt WD, Weissler MC, Turk BF, Gilmer TM. Oncogene amplification in squamous cell carcinoma of the head and neck; Arch Otolaryngol Head Neck Surg 1990;116:1394–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Berenson JR, Yang J, Mickel RA. Frequent amplification of the bc1–1 locus in head and neck squamous cell carcinomas. Oncogene 1989;4:1–1.PubMedGoogle Scholar
  38. 38.
    Jin YSm Higashi K, Mandahl N et al. Frequent rearrangement of chromosomal bands 1p22 and 11q13 in squamous cell carcinomas of the head and neck. Genese Chromosome Cancer 1990; 2: 198–204.Google Scholar
  39. 39.
    Saranath D, Panchal RG, Nair R et al. Oncogene amplification in squmous cell carcinoma of the oral cavity. Jpn J Cancer Res, 1989;80:430–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Garewal H. Chemoprevention of oral cancer: beta-carotene and vitamin E in leukoplakia. Eur J Cancer Prey 1994: 3:101–7.CrossRefGoogle Scholar
  41. 41.
    Garewal HS, Meyskens F, Friedman S, Algerts D, Ramsey L. Oral cancer prevention: the case for carotenoids and antioxidant nutrients. Prey Med 1993: 22:701–11.CrossRefGoogle Scholar
  42. 42.
    Garewal HS, Meyskens FL, Killen D, et al Response of oral leukoplakia to beta-carotene. J. CLinic Oncol 1990 8: 1715–20.Google Scholar
  43. 43.
    Inoue I., Yamamoto Y, Takasaki T., Takahashi H. Inhibitory effects of selenium, vitamin A and butylated hydroxytoluene on in vitro growth of human tongue cancer cells. Eur Arch Otorhinolaryngol 1995, 252:509–512.PubMedCrossRefGoogle Scholar
  44. 44.
    Hong WK, Endicott J, Itri L et al. 13 c-s-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 1986: 56:1242–5.Google Scholar
  45. 45.
    Hong WK, Lippman SM, Itri LM et al. Prevention of second primary tumors with isoretinoin in squamous-cell carcinoma of the head and neck. N. Engl J. Med 1991: 323:795–801.CrossRefGoogle Scholar
  46. 46.
    Amos, B and Lotan R. Retinoid sensitive cells and cell lines. Methods Enzymol, 1991; 190:217–225.CrossRefGoogle Scholar
  47. 47.
    Fanjul A, Dawson MI, Hobbs PD, Jong L, Cameron JF, Harley E et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature 1994: 372:107–111.PubMedCrossRefGoogle Scholar
  48. 48.
    Lippman S M, Benner SE, and Wong WK. Cancer chemoprevention J. Clin. Oncol, 1994: 12:851–873.PubMedGoogle Scholar
  49. 49.
    Amos B and Lotan R. Retinoid sensitive cells and cell lines. Methods Enzymol, 190: 217–225, 1991.CrossRefGoogle Scholar
  50. 50.
    Gudas LJ, Sporn MB and Roberts AB. Cellular biology and biochemistry of retinoids. In: MD Sporn, A Roberts and D S Goodman eds. The Retinoids, pp443–520, New York: Raven Press, 1994.Google Scholar
  51. 51.
    Roberts, AB and Sporn MD. Mechanistic interrelationships between two superfamilies: the steroid/retinoid receptors and transforming growth factor-B. Cancer Surv., 1992, 14:204–220.Google Scholar
  52. 52.
    Leid M, Kastner P, Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci, 1992; 17:427–433.PubMedCrossRefGoogle Scholar
  53. 53.
    Petkovich M, Brand NJ, Krust A, Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature, 1987; 330:444–459.PubMedCrossRefGoogle Scholar
  54. 54.
    Xu XC, Ro JY, Lee JS, Shin DM, Hong WK, Lotan R. Differential expression of nuclear retinoid receptors in normal, premalignant and malignant head and neck tissues. Cancer Res, 1994; 54:3580–3587.PubMedGoogle Scholar
  55. 55.
    Hicks, RM. The scientific basis for regarding vitamin A and its analogs as anticarcinogenic agents. Proc. Nutr Soc, 1983; 43:83–93.CrossRefGoogle Scholar
  56. 56.
    Moon, RC, Itri L. Retinoids and cancer. In Spom MB, Roberts AB, Goodman DS EDs. The Retinoids. Orlando, FL; Academic Press, pp327–371, 1984.Google Scholar
  57. 57.
    Shklar G, Scwartz J, Grau D, Trickier DP, Wallace KD. Inhibition of hamster buccal pouch carcinogenesis by 13-cic-retinoic acid. Oral Surg, 1980; 50:45–52.PubMedCrossRefGoogle Scholar
  58. 58.
    Stich HF, Hornby AP, Mathew B, Sankaranarayanan and Nair MK. Reponse of oral leukoplakias to the administration of vitamin A. Cancer Letters, 1988: 40:93–101.PubMedCrossRefGoogle Scholar
  59. 59.
    Shah JP, Strong EW, DeCosse JJ et al, Effects of retinoids on oral leukoplakia. Am J. Surg. 1983; 146:466–470.PubMedCrossRefGoogle Scholar
  60. 60.
    Kaugars G, Silverman S. The use of 13-cis-retinoic acid in the treatment of oral leukoplakia:short-term observations. Oral Surg. Oral Med Oral Pathol. 1995; 79:264–265.Google Scholar
  61. 61.
    Hong WK, Endicott J, Itri L, Doos W, Bataski JG, Bell R, Fofonoff S, Byers R, Atkinson EN, Vaughan C, Toth BB, Kramer A, Dimery IW, Skipper P, Strong S. 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986; 315:1501–1505.PubMedCrossRefGoogle Scholar
  62. 62.
    Lippman SM, Batsakis B, Toth B et al. Comparison of Low-dose Isotretinoin with beta-carotene to prevent oral carcinogenesis. N Eng J Med. 1993; 328:15–20.CrossRefGoogle Scholar
  63. 63.
    Newton et al Structure activity relationships of retinoids in hamster tracheal organ culture. Cancer Res. 1980; 40:3413–3425.PubMedGoogle Scholar
  64. 64.
    Costa A, Formelli F, Chiesa F, Decensi A De Palo G, Veronesi U. Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide. Cancer Research. 1994; 54:2032s-2037s.PubMedGoogle Scholar
  65. 65.
    Gridley, et al. Diet and oral pharyngeal cancer among blacks,.Nutr. Canc, 1990; 14:219–225.Google Scholar
  66. 66.
    McLaughlin JK, Gridley G, Black G, Winn DM, Preston-Martin S, Schoenberg et al. Dietary factors in oral and pharyngeal cancer. J. Natl Cancer Inst. 1988; 80:1237–1243.PubMedCrossRefGoogle Scholar
  67. 67.
    Zheng WWW, Blot J, Diamond EL et al. Serum micronutrients and the subsequent risk of oral and phaymgeal cancer. Cancer Res. 1993; 53:795–798.PubMedGoogle Scholar
  68. 68.
    Garewal HS, Kleyskens FL, Killen D et al. Response of oral leukoplakia to beta-carotene, J Clin Oncol. 1990; 8:1715–1720.PubMedGoogle Scholar
  69. 69.
    Blot W, Chow WH, McLaughlin JK. Tea and cancer: a review of the epidemiologic evidence. Eur J Cancer Prevent. 1996; 5:425–438.Google Scholar
  70. 70.
    Yang CS, Wang ZY. Tea and cancer: A review. JNCI. 1993; 85:1038–1049.CrossRefGoogle Scholar
  71. 71.
    Yang CS, Wang ZY. Tea and Cancer. A review. JNCI. 1993:85:1038–1049.CrossRefGoogle Scholar
  72. 72.
    Stich HF. Teas and tea components as inhibitors of carcinogen formation in model systems and man. Prevent Med. 1992;21:377–384.CrossRefGoogle Scholar
  73. 73.
    The Indian-US Head and Neck Cancer Cooperative Group, Green Tea and leukoplakia. Am J of Surg, 1997; 174: 552–554.CrossRefGoogle Scholar
  74. 74.
    Inoue I, Yamanto Y, Takasaki T, Takasaki H. Inhibitory effects of selenium, vitamin A and butylated hydroxytoluene on invitro growth of human tongue cancer cells. Eur Arch Otorhinolaryngol. 1995; 252:509–512.PubMedCrossRefGoogle Scholar
  75. 75.
    Lingen M, Polverini P, Bouck N. Retinoic Acid and Interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma. Cancer Research. 1998; 58:5551–5558.PubMedGoogle Scholar
  76. 76.
    Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff D, Kim, D. ONYX015, an EB1 gene-attenuated adenoevirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherpeutic agents, Nature Medicine. 1997; 3:639–645.PubMedCrossRefGoogle Scholar
  77. 77.
    Hong WK, Lippman SM, Itri LM, et al. Prevention of Second Primary Tumors with Isoretinoin in Squamous-cell Carcinoma of the Head and Neck. N Eng J Med. 1990; 323:795–801.CrossRefGoogle Scholar
  78. 78.
    Kim et al. Secondary primary tumor incidence related to primary tumor indices and smoking status in a randomized chemoprevention study of head and neck squamous cell cancer, ASCO 2000, 1642.Google Scholar
  79. 79.
    Bolla M, Lefur R, Ton Van J. Prevention of second primary tumors with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. results of a multicentric double-blind randomized study. European J of Cancer. 1994; 30A:767–772.CrossRefGoogle Scholar

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© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Ann Mellott
  • Everett Vokes

There are no affiliations available

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