Current Oncology Reports

, Volume 8, Issue 2, pp 130–139 | Cite as

The role of human papillomavirus in squamous carcinoma of the head and neck

Article

Abstract

Human papillomavirus type-16 infection is associated with a significant portion of squamous carcinoma of the head and neck, particularly for the oropharynx and for those lacking the other risk factors of tobacco and alcohol. The link between human papillomavirus type-16 and carcinoma of the oropharynx is based on the identification of human papillomavirus type-16 in oropharyngeal tumors and the association of human papillomavirus type-16 with the risk of oropharyngeal cancer estimated in case-control epidemiologic studies. This review highlights the molecular mechanism of human papillomavirus carcinogenesis and the association of human papillomavirus type-16 as a risk factor for squamous cell carcinoma of the oropharynx as well as recent research efforts utilizing human papillomavirus as a biomarker of clinical outcomes.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Mosher WD, Chandra A, Jones J: Sexual Behavior and Selected Health Measures: Men and Women 15–44 Years of Age, United States, 2002. Hyattsville, MD: National Centers for Health Statistics. Advanced Data from Vital and Health Statistics, no. 362; 2005.Google Scholar
  2. 2.
    Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000, 92:709–720. This excellent article discusses the association of oropharyngeal cancers with HPV infection. It provides strong evidence that HPV positivity significantly improved disease-free survival and that HPV-associated oropharyngeal cancers are distinct molecular, clinical, and epidemiologic diseases.PubMedCrossRefGoogle Scholar
  3. 3.
    Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 2001, 344:1125–1131. A case-control study providing strong evidence that HPV-16 infection may be a risk factor for head and neck cancers.PubMedCrossRefGoogle Scholar
  4. 4.
    Vokes EE, Weichselbaum RR, Lippman SM, Hong WK: Head and neck cancer. N Engl J Med 1993, 328:184–194.PubMedCrossRefGoogle Scholar
  5. 5.
    Jemal A, Murray T, Ward E, et al.: Cancer statistics, 2005. CA Cancer J Clin 2005, 55:10–30.PubMedGoogle Scholar
  6. 6.
    Sturgis EM, Wei Q, Spitz MR: Descriptive epidemiology and risk factors for head and neck cancer. Semin Oncol 2004, 31:726–733.PubMedCrossRefGoogle Scholar
  7. 7.
    Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP: Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005, 114:806–808.PubMedCrossRefGoogle Scholar
  8. 8.
    SEER Cancer Statistics Review 1975–2002, 2005. http://seer.cancer.gov/. Accessed November 3, 2005.Google Scholar
  9. 9.
    Shiboski CH, Schmidt BL, Jordan RC: Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20–44 years. Cancer 2005, 103:1843–1849. This interesting study indicates that there is an increasing trend of incidence of squamous cell carcinoma of the tonsil and tongue in the US young population (ages 20–44 years).PubMedCrossRefGoogle Scholar
  10. 10.
    Winn DM: Smokeless tobacco and aerodigestive tract cancers: recent research directions. Adv Exp Med Biol 1992, 320:39–46.PubMedGoogle Scholar
  11. 11.
    Franceschi S, Levi F, La Vecchia C, et al.: Comparison of the effect of smoking and alcohol drinking between oral and pharyngeal cancer. Int J Cancer 1999, 83:1–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Falk RT, Pickle LW, Brown LM, et al.: Effect of smoking and alcohol consumption on laryngeal cancer risk in coastal Texas. Cancer Res 1989, 49:4024–4029.PubMedGoogle Scholar
  13. 13.
    Schlecht NF, Franco EL, Pintos J, Kowalski LP: Effect of smoking cessation and tobacco type on the risk of cancers of the upper aero-digestive tract in Brazil. Epidemiol 1999, 10:412–418.CrossRefGoogle Scholar
  14. 14.
    Spitz MR: Epidemiology and risk factors for head and neck cancer. Semin Oncol 1994, 21:281–288.PubMedGoogle Scholar
  15. 15.
    Schlecht NF, Franco EL, Pintos J, et al.: Interaction between tobacco and alcohol consumption and the risk of cancers of the upper aero-digestive tract in Brazil. Am J Epidemiol 1999, 150:1129–1137.PubMedGoogle Scholar
  16. 16.
    Foulkes WD, Brunet JS, Sieh W, et al.: Familial risks of squamous cell carcinoma of the head and neck: retrospective case-control study. Br Med J 1996, 313:716–721.Google Scholar
  17. 17.
    Schantz SP, Byers RM: The implication of tobacco use in the young adult with head and neck cancer. Cancer 1988, 62:1374–1380.PubMedCrossRefGoogle Scholar
  18. 18.
    Koch WM, McQuone S: Clinical and molecular aspects of squamous cell carcinoma of the head and neck in the nonsmoker and nondrinker. Curr Opin Oncol 1997, 9:257–261.PubMedGoogle Scholar
  19. 19.
    Evander M, Frazer IH, Payne E, et al.: Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J Virol 1997, 71:2449–2456.PubMedGoogle Scholar
  20. 20.
    Bernard HU: The clinical importance of the nomenclature, evolution and taxonomy of human papillomaviruses. J Clin Virol 2005, 32(Suppl1):S1–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Munoz N, Bosch FX, de Sanjose S, et al.: International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003, 348:518–527.PubMedCrossRefGoogle Scholar
  22. 22.
    Schiffman MH, Bauer HM, Hoover RN, et al.: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 1993, 85:958–964.PubMedCrossRefGoogle Scholar
  23. 23.
    Park JS, Hwang ES, Park SN: Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol 1997, 65:121–129.PubMedCrossRefGoogle Scholar
  24. 24.
    Wiest T, Schwarz E, Enders C, et al.: Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 2002, 21:1510–1517.PubMedCrossRefGoogle Scholar
  25. 25.
    Hafkamp HC, Speel EJ, Haesevoets A, et al.: A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5–8. Int J Cancer 2003, 107:394–400.PubMedCrossRefGoogle Scholar
  26. 26.
    Gillison ML: Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol 2004, 31:744–754.PubMedCrossRefGoogle Scholar
  27. 27.
    Wilczynski SP, Lin BT, Xie Y, Paz IB: Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma. Am J Pathol 1998, 152:145–156.PubMedGoogle Scholar
  28. 28.
    Scully C, Field JK, Tanzawa H: Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol 2000, 36:256–263.PubMedCrossRefGoogle Scholar
  29. 29.
    Yang A, Walker N, Bronson R, et al.: p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 2000, 404:99–103.PubMedCrossRefGoogle Scholar
  30. 30.
    Street D, Delgado G: The role of p53 and HPV in cervical cancer. Gynecol Oncol 1995, 58:287–288.PubMedCrossRefGoogle Scholar
  31. 31.
    Tjalma WA, Arbyn M, Paavonen J, et al.: Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer. Int J Gynecol Cancer 2004, 14:751–761.PubMedCrossRefGoogle Scholar
  32. 32.
    Crook T, Tidy JA, Vousden KH: Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 1991, 67:547–556.PubMedCrossRefGoogle Scholar
  33. 33.
    Vousden KH, Lu X: Live or let die: the cell’s response to p53. Nat Rev Cancer 2002, 2:594–604.PubMedCrossRefGoogle Scholar
  34. 34.
    Chellappan S, Kraus VB, Kroger B, et al.: Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci U S A 1992, 89:4549–4553.PubMedCrossRefGoogle Scholar
  35. 35.
    Hawley-Nelson P, Vousden KH, Hubbert NL, et al.: HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 1989, 8:3905–3910.PubMedGoogle Scholar
  36. 36.
    Song S, Liem A, Miller JA, Lambert PF: Human papillomavirus types 16 E6 and E7 contribute differently to carcinogenesis. Virology 2000, 267:141–150.PubMedCrossRefGoogle Scholar
  37. 37.
    Tjalma WA, van Waes TR, van den Eeden LE, Bogers JJ: Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix. Best Practice Res Clin Obstet Gynecol 2005, 19:469–483.CrossRefGoogle Scholar
  38. 38.
    Castle PE, Giuliano AR: Chapter 4: Genital tract infections, cervical inflammation, and antioxidant nutrients—assessing their roles as human papillomavirus cofactors. J Natl Cancer Inst Monogr 2003, 31:29–34.PubMedGoogle Scholar
  39. 39.
    Syrjanen K, Syrjanen S, Lamberg M, et al.: Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis. Int J Oral Surg 1983, 12:418–424. This is the first study to demonstrate the role of HPV in squamous carcinoma of the head and neck.PubMedGoogle Scholar
  40. 40.
    Loning T, Ikenberg H, Becker J, et al.: Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA. J Invest Dermatol 1985, 84:417–420. This study was the first to show the detection of HPV-16 in oral squamous carcinoma by Southern blot hybridization.PubMedCrossRefGoogle Scholar
  41. 41.
    Balz V, Scheckenbach K, Gotte K, et al.: Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2–11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens. Cancer Res 2003, 63:1188–1191.PubMedGoogle Scholar
  42. 42.
    Ritchie JM, Smith EM, Summersgill KF, et al.: Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 2003, 104:336–344.PubMedCrossRefGoogle Scholar
  43. 43.
    Klussmann JP, Gultekin E, Weissenborn SJ, et al.: Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol 2003, 162:747–753.PubMedGoogle Scholar
  44. 44.
    Gillison ML, Koch WM, Shah KV: Human papillomavirus in head and neck squamous cell carcinoma: Are some head and neck cancers a sexually transmitted disease? Curr Opin Oncol 1999, 11:191–199.PubMedCrossRefGoogle Scholar
  45. 45.
    Herrero R, Castellsagué X, Pawlita M, et al.: Human papillomavirus and oral cancer: The International Agency for Research on Cancer Multicenter Study. J Natl Cancer Inst 2003, 95:1772–1783. This is an international multicenter study to confirm that HPV-16 was present in more than 90% of HPV-DNA positive tumors.PubMedGoogle Scholar
  46. 46.
    Schwartz SM, Daling JR, Doody DR: Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 1998, 90:1626–1636. This large population-based study indicates the dramatic differences in HPV tumor positivity between squamous carcinoma of oral cavity and SCCOP.PubMedCrossRefGoogle Scholar
  47. 47.
    Kreimer AR, Clifford GM, Boyle P, Franceschi S: Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 2005, 14:467–475. This is an excellent systematic review of HPV types and head and neck cancers according to geographic location and cancer sites.PubMedCrossRefGoogle Scholar
  48. 48.
    Wynder EL, Bross IJ, Feldman RM: A study of the etiological factors in cancer of the mouth. Cancer 1957, 10:1300–1323.PubMedCrossRefGoogle Scholar
  49. 49.
    Hammond EC, Horn D: Smoking and death rates: report on forty-four months of follow-up of 187,783 men. 2. Death rates by cause. JAMA 1958, 166:1294–1308.Google Scholar
  50. 50.
    Cattaruzza MS, Maisonneuve P, Boyle P: Epidemiology of laryngeal cancer. Oral Oncol Eur J Cancer 1996, 32B:293–305.CrossRefGoogle Scholar
  51. 51.
    Vecchia C, Tavani A, Franceschi S, et al.: Epidemiology and prevention of oral cancer. Oral Oncol 1997, 33:302–312.PubMedCrossRefGoogle Scholar
  52. 52.
    Strome SE, Savva A, Brissett AE, et al.: Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations. Clin Cancer Res 2002, 8:1093–1100. This case-control study showed a strong association of HPV-16 with risk of SCCOP.PubMedGoogle Scholar
  53. 53.
    Smith EM, Hoffman HT, Summersgill KS, et al.: Human papillomavirus and risk of oral cancer. Laryngoscope 1998, 108:1098–1103.PubMedCrossRefGoogle Scholar
  54. 54.
    Chang KC, Su IJ, Tsai ST, et al.: Pathological features of betel quid-related oral epithelial lesions in Taiwan with special emphasis on the tumor progression and human papillomavirus association. Oncology 2002, 63:362–369.PubMedCrossRefGoogle Scholar
  55. 55.
    Smith EM, Summersgill KF, Allen J, et al.: Human papillomavirus and risk of laryngeal cancer. Ann Otol Rhinol Laryngol 2000, 109:1069–1076.PubMedGoogle Scholar
  56. 56.
    Smith EM, Ritchie JM, Summersgill KF: Human papillomavirus in oral exfoliated cells and risk of head and neck cancer. J Natl Cancer Inst 2004, 96:449–455.PubMedCrossRefGoogle Scholar
  57. 57.
    Dahlstrom KR, Adler-Storthz K, Etzel CJ, et al.: Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res 2003, 9:2620–2626.PubMedGoogle Scholar
  58. 58.
    Van Doornum GJ, Korse CM, Buning-Kager JC, et al.: Reactivity to human papillomavirus type 16 L1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites. Br J Cancer 2003, 88:1095–1100.PubMedCrossRefGoogle Scholar
  59. 59.
    Smith EM, Ritchie JM, Summersgill KF, et al.: Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer 2004, 108:766–772.PubMedCrossRefGoogle Scholar
  60. 60.
    Pakarian F, Kaye J, Cason J, et al.: Cancer associated human papillomaviruses: perinatal transmission and persistence. Br J Obstet Gynecol 1994, 101:514–517.Google Scholar
  61. 61.
    Ringstrom E, Peters E, Hasegawa M, et al.: Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 2002, 8:3187–3192.PubMedGoogle Scholar
  62. 62.
    Mellin H, Dahlgren L, Munck-Wikland E, et al.: Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer 2002, 102:152–158.PubMedCrossRefGoogle Scholar
  63. 63.
    Hafkamp HC, Manni JJ, Speel EJ: Role of human papillomavirus in the development of head and neck squamous cell carcinomas. Acta Otolaryngol 2004, 124:520–526.PubMedCrossRefGoogle Scholar
  64. 64.
    Badaracco G, Venuti A, Morello R, et al.: Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. Anticancer Res 2000, 20:1301–1305.PubMedGoogle Scholar
  65. 65.
    Lindel K, Beer KT, Laissue J, et al.: Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 2001, 92:805–813.PubMedCrossRefGoogle Scholar
  66. 66.
    Pintos J, Franco EL, Black MJ, et al.: Human papillomavirus and prognoses of patients with cancers of the upper aerodigestive tract. Cancer 1999, 85:1903–1909.PubMedGoogle Scholar
  67. 67.
    Mellin H, Friesland S, Lewensohn R, et al.: Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 2000, 89:300–304.PubMedCrossRefGoogle Scholar
  68. 68.
    Schwartz SR, Yueh B, McDougall JK, et al.: Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 2001, 125:1–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Báez A, Almodóvar JI, Cantor A, et al.: High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican population. Head Neck 2004, 26:778–784.PubMedCrossRefGoogle Scholar
  70. 70.
    Clayman GL, Stewart MG, Weber RS: Human papillomavirus in laryngeal and hypopharyngeal carcinomas. Relationship to survival. Arch Otolaryngol Head Neck Surg 1994, 120:743–748.PubMedGoogle Scholar
  71. 71.
    Koskinen WJ, Chen RW, Leivo I: Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int J Cancer 2003, 107:401–406.PubMedCrossRefGoogle Scholar
  72. 72.
    Pytynia KB, Grant JR, Etzel CJ, et al.: Matched-pair analysis of survival of never smokers and ever smokers with squamous cell carcinoma of the head and neck. J Clin Oncol 2004, 22:3981–3988.PubMedCrossRefGoogle Scholar
  73. 73.
    Lin JC, Wang WY, Chen KY, et al.: Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 2004, 350:2461–2470.PubMedCrossRefGoogle Scholar
  74. 74.
    Lo YMD, Chan L, Chan A, et al.: Quantitative and temporal correlation between circulating cell-free Epstein-Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma. Cancer Res 1999, 59:5452–5455.PubMedGoogle Scholar
  75. 75.
    Lin JC, Chen K, Wang WY, et al.: Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival. J Clin Oncol 2001, 19:2607–2615.PubMedGoogle Scholar
  76. 76.
    Lo YMD, Chan A, Chan L, et al.: molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res 2000, 60:6878–6881.PubMedGoogle Scholar
  77. 77.
    Mutirangua A, Pornthanakasem W, Theamboonlers A, et al.: Epstein-Barr viral DNA in serum of patients with nasopharyngeal carcinoma. Clin Cancer Res 1998, 4:665–669.Google Scholar
  78. 78.
    Wang WY, Chien YC, Jan JS, et al.: Consistent sequence variation of Epstein-Barr virus nuclear antigen 1 in primary tumor and peripheral blood cells of patients with nasopharyngeal carcinoma. Clin Cancer Res 2002, 8:2586–2590.PubMedGoogle Scholar
  79. 79.
    Chan A, Lo Y, Zee B, et al.: Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst 2002, 94:1614–1619.PubMedGoogle Scholar
  80. 80.
    Widschwendter A, Blassnig A, Wiedemair A, et al.: Human papillomavirus DNA in sera of cervical cancer patients as tumor marker. Cancer Lett 2003, 202:231–239.PubMedCrossRefGoogle Scholar
  81. 81.
    Pornthanakasem W, Shotelersuk K, Termrungruanglert W, et al.: Human papillomavirus DNA in the plasma of patients with cervical cancer. BMC Cancer 2001, 1:2.PubMedCrossRefGoogle Scholar
  82. 82.
    Tseng CJ, Pao CC, Lin JD, et al.: Detection of human papillomavirus types 16 and 18 mRNA in peripheral blood of advanced cervical cancer patients and its association with prognosis. J Clin Oncol 1999, 17:1391–1396.PubMedGoogle Scholar
  83. 83.
    Capone RB, Pai SI, Koch WM, et al.: Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma. Clin Cancer Res 2000, 6:4171–4175. This interesting study demonstrates the potential of serum HPV as biomarker for risk of recurrence or distant metastases among head and neck cancer patients.PubMedGoogle Scholar
  84. 84.
    Koutsky LA, Ault KA, Wheeler CM, et al.: A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002, 347:1645–1651.PubMedCrossRefGoogle Scholar
  85. 85.
    Kahn JA, Bernstein DI: Human papillomavirus vaccines and adolescents. Curr Opin Obstet Gynecol 2005, 17:476–482.PubMedCrossRefGoogle Scholar
  86. 86.
    Devaraj K, Gillison ML, Wu TC: Development of HPV vaccines for HPV-associated head and neck squamous cell carcinoma. Crit Rev Oral Biol Med 2003, 14:345–362.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.Department of Head and Neck Surgery, Unit 441The University of Texas M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations