1. GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC Cancer Base No. 5. Lyon, 2001 IARC Press. 2 Stewart BW, Kleihues PE: World Cancer Report. Lyon, France, International Agency for Research on Cancer Press, 2003. 3 Ferlito A, Rinaldo A, Devaney KO, MacLennan K, Myers JN, Petruzzelli GJ, et al. Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes. Review. Oral Oncol 2002;38:747-51. 4 Jose J, Coatesworth AP, Johnston C, MacLennan K. Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits. Head Neck 2003;25:451-6. 5 Thomas GR, Nadiminti H, REgalado J. Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol 2005;86:347-63. 6 Brennan JA, Mao L, Hruban RH, Boyle JO, Eby YJ, Koch WM, et al. Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N Engl J Med 1995;332:429-35. 7 Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet 2008; 371:1695–709. 8 Linkov F, Lisovich A, Yurkovetsky Z, Marrangoni A, Velikokhatnaya L, Nolen B et al. Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling. Cancer Epidemiol Biomarkers Prev 2007;16:102–7. 9Thomas G.R, Nadiminti H, Regalado J. Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int. J. Exp. Path. 2005;86:347–363. 10 Nogueira C., Dolan R.W., Gooey J. et al. Inactivation of P53 and amplification of cyclin D1 correlate with clinical outcome in head and neck cancer. Laryngoscope 1998; 108:345–350. 11Edstrom S., Cvetkovska E., Westin T., Young C. et al. Overexpression of p53-related proteins predicts rapid growth rate of head and neck cancer. Laryngoscope 2001;111: 124–130. 12Koch W., Brennan J., Zahurak M. et al. P53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma. J. Natl. Cancer Inst 1996;88:1580–1586. 13 Erber R., Conradt C., Homann N. et al. TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer. Oncogene 1998;16:1671–1679. 14Ma L., Ronai A., Riede U., Kohler G. Clinical implication of screening P53 gene mutations in head and neck squamous cell carcinomas. J. Cancer Res. Clin. Oncol. 1998;124:389–396. 15Khademi B., Shirazi F., Vasei M. et al. The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors. Cancer Lett. 2002;184:223–230. 16 Vielba R., Bilbao J., Ispizua A. et al. p53 and cyclin D1 as prognostic factors in squamous cell carcinoma of the larynx. Laryngoscope 2003;113:167–172. 17 De Vicente C., Junquera Gutierrez. L., Zapatero A. et al. Prognostic significance of p53 expression in oral squamous cell carcinoma without neck node metastases. Head Neck 2004;26:22–30. 18Perrone F, Bossi P, Cortellazzi B, et al. TP53 Mutations and Pathologic Complete Response to Neoadjuvant Cisplatin and Fluorouracil Chemotherapy in Resected Oral Cavity Squamous Cell Carcinoma. 2010; 28(5):761-766. 19 Gonzalez M., Pello M., Lopez-Larrea C., Suarez C., Menendez M., Coto E. Deletion and methylation of the tumour suppressor gene P16/CDKN2 in primary head and neck squamous cell carcinoma. J. Clin. Pathol. 1997;50:509–512. 20 Rawnsley J., Srivatsan E., Chakrabarti R., Billings K., Wang M. Deletion analysis of the p16/CDKN2 gene in head and neck squamous cell carcinoma using quantitative polymerase chain reaction method. Arch. Otolaryngol. Head Neck Surg. 1997;123:863–867. 21 Reed A., Califano J., Cairns P. et al. High frequency of P16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res. 1996;56:3630–3633. 22 Miracca E.C., Kowalski L.P., Nagai M.A. High prevalence of P16 genetic alterations in head and neck tumours. Br. J. Cancer 1999;81:677–683. 23Rischin D, Young RJ, Fisher R, et al. Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial. Clin Oncol 2010;28(27):4142-4148. 24 Chau NG, Perez.Ordonez B, Zhang K. The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Head & Neck Oncology 2011;3:11. 25 Santini J, Formento JL, Francoual M, et al: Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. Head Neck 13:132-139, 1991 26 Salomon DS, Brandt R, Ciardiello F, et al: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232. 27 Grandis JR, Tweardy DJ: TGF-alpha and EGFR in head and neck cancer. J Cell Biochem 1993 Suppl 17F:188-191. 28 Rubin Grandis J, Melhem MF, Gooding WE, et al: Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 1998; 90:824-832. 29 Ang KK, Berkey BA, Tu X, et al: Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 2002;62:7350-7356. 30 Aboud-Pirak, E., Hurwitz, E., Pirak, M.E., Bellot, F., Schlessinger, J., Sela, M., Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J. Natl. Cancer Inst. 1998;80:1605–1611. 31 Baselga, J., Norton, L., Masui, H., Pandiella, A., Coplan, K., Miller Jr., W.H., Mendelsohn, J., Anti-tumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J. Natl. Cancer Inst. 1993; 85:327–1333. 32 Burtness BA, Goldwasser MA, Flood W, et al: 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. J Clin Oncol 2005; 23: 8646-8654. 33 Vermoken JB, Mesia R, Rivera F et al. Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer. N Engl J Med 2008;359:1116-27. 34 Licitra L, Mesia L, Rivera F. Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Annals of Oncology 2011; 22:1078–1087. 35 Teknos T., Cox C., Yoo S. et al. Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma. Head Neck 2002;24: 1004–1011. 36 Tanigaki Y., Nagashima Y., Kitamura Y.,Matsuda H., Mikami Y., Tsukuda M. The expression of vascular endothelial growth factor-A and -C, and receptors 1 and 3: correlation with lymph node metastasis and prognosis in tongue squamous cell carcinoma. Int. J. Mol. Med. 2004; 14: 389–395. 37 Tania Crombet, Marta Osorio, Teresa Cruz, Carlos Roca, Ramo´n del Castillo, Rosa Mon, Normando Iznaga-Escobar, René Figueredo, James Koropatnick, Enrique Renginfo, Eduardo Ferna´ndez, Daniel Alva´rez, Olga Torres, Mayra Ramos, Idrissa Leonard, Rolando Pérez, and Agustín Lage. Use of the Humanized Anti-Epidermal Growth Factor Receptor Monoclonal Antibody h-R3 in Combination With Radiotherapy in the Treatment of Locally Advanced Head and Neck Cancer Patients. J of Clinical Oncology 2004; 22 (9): 1646-1654. 38 Melarkode S. Ramakrishnan, ,* Anand Eswaraiah, Tania Crombet, Patricia Piedra, Giselle Saurez, Harish Iyer1 and A.S. Arvind. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial Origin. Mabs 2009 1:1, 41-48. 39 Marta Osorio Rodríguez, Teresa Cruz Rivero, Ramón del Castillo Bahi, Carlos Roca Muchuli, Miguel Azcue Bilbao, Elia Neninger Vinageras, José Alert, Julio Jiménez Galainena, Edmundo Rodríguez, Elías Gracia, Bárbara Mulén, Bárbara Wilkinson, Esther Lucía de Armas, Kirenia Pérez, Idael Pineda,4 Milagros Frómeta, Idrissa Leonard, Vladimir Mullens, Carmen Viada, Patricia Luaces, Olga Torres, Normando Iznaga and Tania Crombet. Cancer Biology and Therapy 2010, 9: 5, 343-349 40 Selenko N, Maidic O, Draxier S, Berer A, Jäger U, Knapp W, Stöckl J. CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells. Leukemia. 2001 Oct;15(10):1619-26. 41 Lee SC, Srivastava RM, López-Albaitero A, Ferrone S, Ferris RL. Natural killer (NK): dendritic cell (DC) cross talk induced by therapeutic monoclonal antibody triggers tumor antigen-specific T cell immunity. Immunol Res. 2011 Aug;50(2-3):248-54. Review 42 Hilchey SP, Hyrien O, Mosmann TR, Livingstone AM, Friedberg JW, Young F, Fisher RI, Kelleher RJ Jr, Bankert RB, Bernstein SH. Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab. Blood. 2009 Apr 16;113 (16) : 3809-12.