IJOHNS  Vol.3 No.5 , September 2014
A Review of Literature Pertaining to Head and Neck Squamous Cell Carcinoma with Emphasis on the Role of the Human Papilloma Virus
Abstract: Over the last decades the United Kingdom has seen a general increase in the incidence of head and neck squamous cell carcinoma (HNSCC). In addition to the classical risk factors of smoking and alcohol consumption there now appears that a viral aetiology is attributed to a significant proportion of HNSCC. A number of studies have indicated that human papillomavirus (HPV) infection is implicated with the subtype HPV 16 being found in many histopathological specimens. Further evidence suggests that HPV positive status is a prognostic factor related to a favourable outcome in head and neck cancers. This premise may have a significant impact on our approach to treating HNSCC. Patients belonging to stages I/II are traditionally treated with curative intent, single modality treatments that are either radiation or surgery alone. These treatment regimens are relatively aggressive and may lead to severe functional impairment. HPV patients may not require such an approach. This dissertation examines the current evidence which has given rise to these assertions, and explores the unresolved issues preventing HPV positive status becoming part of the management convention. The methodology involved a comprehensive literature review. The literature conclusions and limitations are discussed with reference to what is becoming accepted universally in this field and what remains to be elucidated. The different prognosis and treatment reaction to radiotherapy and chemotherapy by HPV positive tumours could be extrapolated to suggest that HPV status detection is required to plan treatment regimes. Indeed a separate subset of patients could potentially be categorised with an improvement in morbidity.
Cite this paper: Cartwright, S. (2014) A Review of Literature Pertaining to Head and Neck Squamous Cell Carcinoma with Emphasis on the Role of the Human Papilloma Virus. International Journal of Otolaryngology and Head & Neck Surgery, 3, 279-292. doi: 10.4236/ijohns.2014.35051.

[1]   Jemal, A., Seigel, R., Ward, E., et al. (2007) Cancer Statistics. CA: A Cancer Journal for Clinicians, 57, 43-66.

[2]   Sturgis, E.M., Wei, Q. and Spitz, M.R. (2004) Descriptive Epidemiology and Risk Factors for Head and Neck Cancer. Seminars in Oncology, 31, 726-733.

[3]   Munger, K. and Howley, P.M. (2002) Human Papilloma Virus Immortalization and Transformation Functions. Virus Research, 89, 213-218.

[4]   Hobbs, C.G., Sterne, J.A.C., Bailey, M., Heyderman, R.S., Birchall1, M.A. and Thomas, S.J. (2006) Human Papilloma Virus and Head and Neck Cancer: A Systematic Review and Meta-Analysis. Clinical Otolaryngology, 31, 259-266.

[5]   Palka, K.T., Slebos, R.J. and Chungemail, C.H. (2008) Update on Molecular Diagnostic Tests in Head and Neck Cancer. Seminars in Oncology, 35, 198-210.

[6]   Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T. and Carbone, P.P. (1982) Toxicity and Response Criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology, 5, 649-655.

[7]   Klozar, J., Kratochvil, V., Salakova, M., Smahelova, J., Vesela, E., Hamsikova, E., Betka, J. and Tachezy, R. (2008) HPV Status and Regional Metastasis in the Prognosis of Oral and Oropharyngeal Cancer. European Archives of Oto-Rhino-Laryngology, 265, S75-S82.

[8]   Kumar, B., Cordell, K.G., Lee, J.S., Prince, M.E., et al. (2007) Response to Therapy Outcomes in Oropharyngeal Cancer Are Associated with Biomarkers Including Human Papilloma Virus, Epidermal Growth Factor, Gender and Smoking. International Journal of Radiation Oncology*Biology*Physics, 69, S109-S111.

[9]   Fakhry, C., Westra, W.H., Li, S.G., Cmelak, A., Ridge, J.A., Pinto, H., Forastiere, A. and Gillison, M.L. (2008) Improved Survival of Patients with Human Papilloma Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial. Journal of the National Cancer Institute, 100, 261-269.

[10]   Weinberger, P.M., Yu, Z.W., Haffty, B.G., Kowalski, D., Harigopal, M., Brandsma, J., Sasaki, C., Joe, J., Camp, R.L., Rimm, D.L. and Psyrri, A. (2006) Molecular Classification Identifies a Subset of Human Papilloma Virus Assocaited Oropharyngeal Cancers with Favourable Prognosis. Journal of Clinical Oncology, 24, 736-747.

[11]   Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T. and Carbone, P (1982) Toxicity and Response Criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology, 5, 649-655.

[12]   American Society of Clinical Oncology.

[13]   Carvalho, A.L., Nishimoto, I.N., Califano, J.A. and Kowalski, L.P. (2005) Trends in Incidence and Prognosis for Head and Neck Cancer in the United States: A Site-Specific Analysis of the SEER Database. International Journal of Cancer, 114, 806-808.

[14]   Oxford Cancer Intelligence Unit (OCIU).

[15]   Mignogna, M.D., Fedele, S. and Russo, L.L. (2004) The World Cancer Report and the Burden of Oral Cancer. European Journal of Cancer Prevention, 13, 139-142.

[16]   Macfarlane, G.J., Zheng, T., Marshall, J.R., Boffetta, P., Niu, S., Brasure, J., Merletti, F. and Boyle, P. (1995) Alcohol, Tobacco, Diet and the Risk of Oral Cancer: A Pooled Analysis of Three Case-Controlled Studies. European Journal of Cancer Part B: Oral Oncology, 318, 181-187.

[17]   Brennan, J.A., Boyle, J.O., Koch, W.M., Goodman, S.N., Hruban, R.H., Eby, Y.J., Couch, M.J., Forastiere, A.A. and Sidransky, D. (1995) Association between Cigarette Smoking and Mutation of the p53 Gene in Squamous-Cell Carcinoma of the Head and Neck. The New England Journal of Medicine, 332, 712-717.

[18]   Syrjänen, K., Syrjänen, S., Lamberg, M., Pyrhönen, S. and Nuutinen, J. (1983) Morphological and Immunohistochemical Evidence Suggesting Human Papilloma Virus (HPV) Involvement in Oral Squamous Cell Carcinogenesis. International Journal of Oral Surgery, 12, 418-424.

[19]   Kreimer, A.R., Clifford, G.M., Boyle, P. and Franceschi, S. (2005) Human Papilloma Virus Types in Head and Neck Squamous Cell Carcimomas Worldwide: A Systematic Review. Cancer Epidemiology, Biomarkers & Prevention, 14, 467-475.

[20]   René Leemans, C., Braakhuis, B.J.M. and Brakenhoff, R.H. (2011) The Molecular Biology of Head and Neck Cancer: HPV-Infected HNSCC. Nature Reviews Cancer, 11, 9-22.

[21]   Hammarstedt, L., Lindquist, D., Dahlstrand, H., Romanitan, M., Dahlgren, L.O., Joneberg, J., Creson, N., Lindholm, J., Ye, W., Dalianis, T. and Munck-Wikland, E. (2006) Human Papillomavirus as a Risk Factor in the Incidence of Tonsillar Cancer. International Journal of Cancer, 119, 2620-2623.

[22]   Termine, N., Panzarella, V., Falaschini, S., Russo, A., Matranga, D., Lo Muzio, L. and Campisi, G. (2008) HPV in Oral Squamous Cell Carinoma vs Head and Neck Squamous Cell Carcinoma Biopsies: A Meta-Analysis (1988-2007). Annals of Oncology, 19, 1681-1690.

[23]   Klussmann, J.P., Weissenborn, S.J., Wieland, U., Dries, V., Kolligs, J., Jungehuelsing, M., Eckel, H.E., Dienes, H.P., Pfister, H.J. and Fuchs, P.G. (2011) Prevalence Distribution and Viral Load of Human Papilloma Virus 16 DNA in Tonsillar Carcinomas. Cancer, 92, 2875-2884.<2875::AID-CNCR10130>3.0.CO;2-7

[24]   Begum, S. and Westra, W.H. (2008) Basaloid Squamous Cell Carcinoma of the Head and Neck Is a Mixed Variant That Can be Further Resolved with HPV Status. The American Journal of Surgical Pathology, 32, 1044-1050.

[25]   Agoston, E.S., Robinson, S.J., Mehra, K.K., Birch, C., Semmel, D., Mirkovic, J., Haddad, R.I., Posner, M.R., Kindelberger, D., Krane, J.F., Brodsky, J. and Crum, C.P. (2010) Polymerase Chain Reaction Detection of HPV in Squamous Carcinoma of the Oropharynx. American Journal of Clinical Pathology, 134, 36-41.

[26]   Burtness, B., Goldwasser, M.A., Flood, W., Mattar, B., Forastiere, A.A. and Eastern Cooperative Oncology Group (2005) Phase III Randomized Trial of Cisplatin plus Placebo Compared with Cisplatin plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology, 23, 8646-8654.

[27]   Royal College of Pathologists (2005) Standards and Datasets for Reporting Cancers: Datasets for Histopathology Reports on Head and Neck Carcinomas and Salivary Neoplasms. 2nd Edition.

[28]   Bourhis, J., Overgaard, J., Audry, H., Ang, K.K., Saunders, M., Bernier, J., et al. (2006) Hyperfractionated or Accelerated Radiotherapy in Head and Neck Cancer: A Meta-Analysis. The Lancet, 368, 843-854.

[29]   Gillison, M.L., Koch, W.M., Capone, R.B., Spafford, M., Westra, W.H., Wu, L., Zahurak, M.L., Daniel, R.W., Viglione, M., Symer, D.E., Shah, K.V. and Sidransky, D. (2000) Evidence for a Causal Association between Human Papilloma Virus and Head and Neck Cancers. Journal of the National Cancer Institute, 92, 709-720.

[30]   Mead, P.H. (2004) Surgery or Radiotherapy for Tonsil Cancer? Cancer, 16, 195-198.<195::AID-CNCR2820160208>3.0.CO;2-7

[31]   Jesse, R.H. and Fletcher, G.H. (1977) Treatment of the Neck in Patients with Squamous Cell Carcinoma of the Head and Neck. Cancer, 39, 868-872.<868::AID-CNCR2820390724>3.0.CO;2-N

[32]   Mendenhall, W.M., Morris, C.G., Amdur, R.J., Hinerman, R.W., Malyapa, R.S., Werning, J.W., Lansford, C.D. and Villaret, D.B. (2006) Definative Radiotherapy for Tonsillar Squamous Cell Carcinoma. American Journal of Clinical Oncology, 29, 290-297.

[33]   Vikram, B. and Farr, H.W. (1983) Adjuvant Radiation Therapy in Locally Advanced Head and Neck Cancer. CA: A Cancer Journal for Clinicians, 33, 134-138.

[34]   McCubbin, M., et al. (2010) Head and Neck Squamous Cell Carcinoma and Human Papillomavirus. Seton Network Notes, 10.

[35]   Cooper, J.S., Pajak, T.F., Forastiere, A.A., Jacobs, J., Campbell, B.H., Saxman, S.B., Kish, J.A., Kim, H.E., Cmelak, A.J., Rotman, M., Machtay, M., Ensley, J.F., Chao, K.S., Schultz, C.J., Lee, N., Fu, K.K. and Radiation Therapy Oncology Group 9501/Intergroup (2004) Post Operative Concurrent Radiotherapy and Chemotherapy for High Risk Squamous Cell Carcinoma of the Head and Neck. The New England Journal of Medicine, 350, 1937-1944.

[36]   Lee, N., Puri, D.R., Blanco, A.I. and Chao, K.S.C. (2007) Intensity-Modulated Radiation Therapy in Head and Neck Cancers: An update. Head and Neck, 29, 387-400.

[37]   Bonner, J.A., Harari, P.M., Giralt, J., et al. (2006) Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck. The New England Journal of Medicine, 354, 567-578.

[38]   Georgetown University Medical Center (2010) Improved Outcomes for HPV-Positive Head and Neck Cancer with Cetuximab and IMRT, Study Suggests.

[39]   Goldenberg, D., Begum, S., Westra, W.H., Khan, Z., Sciubba, J., Pai, S.I., Califano, J.A., Tufano, R.P. and Koch, W.M. (2008) Cystic Lymph Node Metastasis in Patients with Head and Neck Cancer: An HPV-Associated Phenomenon. Head and Neck, 30, 898-903.

[40]   Pai, S.I. and Westra, W.H. (2009) Molecular Pathology of Head and Neck Cancer: Implications for Diagnosis, Prognosis and Treatment. Annual Review of Pathology, 4, 49-70.

[41]   Al-Bakkal, G., Ficarra, G., McNeill, K., Eversole, L.R., Sterrantino, G. and Birek, C. (1999) Human Papilloma Virus Type 16 E6 Gene Expression in Oral Exophytic Epithelial Lesions as Detected in Situ rtPCR. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 87, 197-208.

[42]   The HPV Connection (2010).