Skip to main content

Advertisement

SpringerLink
Log in

A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment

  • Review
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Head and neck cancer is the fifth most common cancer worldwide but the most common malignant disease site in central Asia. The treatment of head and neck cancer is one of the most challenging in clinical oncology because of the high content of hypoxic cells of the cancer which increases resistance to therapy and also because of the high capacity of the cancer to regrow during treatment. For unresectable tumours, radiotherapy and chemotherapy alone or more often in combination is the treatment of choice. The aim of this paper is to review current understanding of carcinogenesis of head and neck cancer in relation to predisposing risk factors in general and for specific sub-sites and how these risk factors interact with the main reported genetic alterations in the progression of the cancer. The implications of these changes in determining choice of therapy are also discussed from a brief historical perspective of the various treatment approaches of head and neck cancer.

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

  • Ai L, Stephenson KK, Ling W, Zuo C, Mukunyadzi P et al (2003) The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases. Mod Pathol 16:944–950. doi:10.1097/01.MP.0000085760.74313.DD

    Article  PubMed  Google Scholar 

  • Al-Sarraf M, Pajak T, Marcial V et al (1987) Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG study. Cancer 59:259–265. doi:10.1002/1097-0142(19870115)59:2<259::AID-CNCR2820590214>3.0.CO;2-1

    Article  CAS  PubMed  Google Scholar 

  • Arias F, Dominguez M, Illarramendi J et al (1995) Split hyperfractionated accelerated radiation therapy and concomitant cisplatin for locally advanced head and neck carcinomas: a preliminary report. Int J Radiat Oncol Biol Phys 33:675–682. doi:10.1016/0360-3016(95)00210-P

    CAS  PubMed  Google Scholar 

  • Bailet JW, Abemayor E, Jabour BA, Hawkins RA et al (1992) Positron emission tomography: a new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy. Laryngoscope 102:281–288

    CAS  PubMed  Google Scholar 

  • Beckmann GK, Hoppe F, Pfreundner L, Flentje MP (2005) Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer. Head Neck 27:36–43. doi:10.1002/hed.20111

    Article  PubMed  Google Scholar 

  • Bedi GC, Westra WH, Gabrielson E et al (1996) Multiple head and neck tumors: evidence for a common clonal origin. Cancer Res 56:2484–2487

    CAS  PubMed  Google Scholar 

  • Berrino F, Richiardi L, Boffetta P, Esteve J et al (2003) Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in an international case-control study in France, Italy, Spain and Switzerland. Cancer Causes Control 14:213–223. doi:10.1023/A:1023661206177

    Article  PubMed  Google Scholar 

  • Bonner JA, Harari PM, Giralt J, Azarnia N et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578. doi:10.1056/NEJMoa053422

    Article  CAS  PubMed  Google Scholar 

  • Brizel DM (1998) Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma. Semin Radiat Oncol 8:237–246. doi:10.1016/S1053-4296(98)80021-0

    Article  CAS  PubMed  Google Scholar 

  • Browman G, Hodson I, Mackenzie R, Bestic N, Zuraw L (2001) Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: a systematic review of the published literature with subgroup analysis. Head Neck 20:579–589. doi:10.1002/hed.1081

    Article  Google Scholar 

  • Califano J, van der RP, Westra W et al (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:2488–2492

  • Caplan LS, Hall HI, Levine RS, Zhu K et al (2000) Preventable risk factors for nasal cancer. Ann Epidemiol 10:186–191. doi:10.1016/S1047-2797(99)00049-6

    Article  CAS  PubMed  Google Scholar 

  • Chen AM, Bucci MK, Quivey JM, Garcia J et al (2006) Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas. Int J Radiat Oncol Biol Phys 66:1044–1050. doi:10.1016/j.ijrobp.2006.06.050

    PubMed  Google Scholar 

  • Closmann JJ (2007) The human papilloma virus, the vaccines, and oral and oropharyngeal squamous cell carcinoma: what every dentist should know. Gen Dent 55(3):252–254

    PubMed  Google Scholar 

  • Creagan E, O’Fallon J, Woods J et al (1983) Cis-diamminedichloroplatinum (II) administered by 24-hour infusion in the treatment of patients with advanced upper aerodigestive cancer. Cancer 51:2020–2023. doi:10.1002/1097-0142(19830601)51:11<2020::AID-CNCR2820511110>3.0.CO;2-X

    Article  CAS  PubMed  Google Scholar 

  • Douglas JG, Laramore GE, Austin-Seymour M, Koh WJ et al (1996) Neutron radiotherapy for adenoid cystic carcinoma of minor salivary glands. Int J Radiat Oncol Biol Phys 36:87–93. doi:10.1016/S0360-3016(96)00213-1

    CAS  PubMed  Google Scholar 

  • Fan KF, Hopper C, Speight PM, Buonaccorsi G et al (1996) Photodynamic therapy using 5-aminolevulinic acid for premalignant and malignant lesions of the oral cavity. Cancer 78:1374–1383. doi:10.1002/(SICI)1097-0142(19961001)78:7<1374::AID-CNCR2>3.0.CO;2-L

    Article  CAS  PubMed  Google Scholar 

  • Feron VJ, Arts JH, Kuper CF, Slootweg PJ et al (2001) Health risks associated with inhaled nasal toxicants. Crit Rev Toxicol 31:313–347. doi:10.1080/20014091111712

    Article  CAS  PubMed  Google Scholar 

  • Fisch U (1983) The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope 93:36–44

    CAS  PubMed  Google Scholar 

  • Fisch U, Fagan P, Valvanis A (1984) The infratemporal fossa approach for the lateral skull base. Otolaryngol Clin North Am 17:513–552

    CAS  PubMed  Google Scholar 

  • Fontanesi J, Beckford NS, Lester EP et al (1991) Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck. Am J Surg 162:393–396. doi:10.1016/0002-9610(91)90156-8

    Article  CAS  PubMed  Google Scholar 

  • Fu KK (1998) Combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Semin Radiat Oncol 8:247–253. doi:10.1016/S1053-4296(98)80022-2

    Article  CAS  PubMed  Google Scholar 

  • Gallicchio L, Matanoski G, Tao XG, Chen L et al (2006) Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review. Int J Cancer 119:1125–1135. doi:10.1002/ijc.21946

    Article  CAS  PubMed  Google Scholar 

  • Garden AS, Harris J, Trotti A, Jones CU et al (2008) Long-term results of concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: a phase II trial of the radiation therapy oncology group (RTOG 99–14). Int J Radiat Oncol Biol Phys 71:1351–1355. doi:10.1016/j.ijrobp.2008.04.006

    PubMed  Google Scholar 

  • Gasparini G, Pozza F, Recher G et al (1991) Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. Oncology 48:270–276

    Article  CAS  PubMed  Google Scholar 

  • Gleich L, Ryzenman J, Gluckman J, Wilson K et al (2004) Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage possible? Arch Otolaryngol Head Neck Surg 130:35–38. doi:10.1001/archotol.130.1.35

    Article  PubMed  Google Scholar 

  • Go SR, Adjei AA (1999) Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol 17(1):409–422

    CAS  PubMed  Google Scholar 

  • Grant WE, Hopper C, Speight PM, Macrobert AJ et al (1993) Photodynamic therapy of malignant and premalignant lesions in patients with ‘field cancerization’ of the oral cavity. J Laryngol Otol 107:1140–1145. doi:10.1017/S0022215100125496

    Article  CAS  PubMed  Google Scholar 

  • Greven KM, Williams DW, Keyes JW Jr, McGuirt WF et al (1994) Positron emission tomography of patients with head and neck carcinoma before and after high dose irradiation. Cancer 74:1355–1359. doi:10.1002/1097-0142(19940815)74:4<1355::AID-CNCR2820740428>3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  • Han D, Huang ZG, Zhang W, Yu ZK et al (2003) Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: phase I clinical trial and follow up. Chin J Cancer Res 83:2029–2032

    CAS  Google Scholar 

  • Hardisson D (2003) Molecular pathogenesis of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 260:502–508. doi:10.1007/s00405-003-0581-3

    Article  PubMed  Google Scholar 

  • Herrero R, Castellsague X, Plissowska J et al (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 95:1772–1783

    PubMed  Google Scholar 

  • Hoppe BS, Stegman LD, Zelefsky MJ, Rosenzweig KE et al (2007) Treatment of nasal cavity and paranasal sinus cancer with modern radiotherapy techniques in the postoperative setting—the MSKCC experience. Int J Radiat Oncol Biol Phys 67:691–702. doi:10.1016/j.ijrobp.2006.09.023

    PubMed  Google Scholar 

  • Jacobs C, Bertino JR, Goffinet DR et al (1978) 24-hour infusion of cis-platinum in head and neck cancers. Cancer 42:2135–2140. doi:10.1002/1097-0142(197811)42:5<2135::AID-CNCR2820420508>3.0.CO;2-W

    Article  CAS  PubMed  Google Scholar 

  • Jeremic B, Shibamoto Y, Milicic B et al (2000) Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18:1458–1464

    CAS  PubMed  Google Scholar 

  • Julieron M, Temam S (2004) Locoregional recurrence of ORL cancer: the place of surgery. Bull Cancer 91:863–869

    PubMed  Google Scholar 

  • Kalyankrishna GJ (2006) Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol 17:2666–2672. doi:10.1200/JCO.2005.04.8306

    Article  Google Scholar 

  • Kato K, Hara A, Kuno T, Mori H et al (2006) Aberrant promoter hypermethylation in oral squamous cell carcinomas and the surrounding normal mucosa. J Cancer Res Clin Oncol 132:735–743. doi:10.1007/s00432-006-0122-8

    Article  CAS  PubMed  Google Scholar 

  • Katz TS, Mendenhall WM, Morris CG, Amdur RJ et al (2002) Malignant tumors of the nasal cavity and paranasal sinuses. Head Neck 24:821–829. doi:10.1002/hed.10143

    Article  PubMed  Google Scholar 

  • Kawashiri S, Noguchi N, Tanaka A, Nakaya H et al (2009) Inhibitory effect of neoadjuvant chemotherapy on metastasis of oral squamous cell carcinoma in a mouse model. Oral Oncol

  • Kim AJ, Suh JD, Sercarz JA, Abemayor E et al (2007) Salvage surgery with free flap reconstruction: factors affecting outcome after treatment of recurrent head and neck squamous carcinoma. Laryngoscope 117:1019:23

    Google Scholar 

  • Kvaal SI, Warloe T (2007) Photodynamic treatment of oral lesions. J Environ Pathol Toxicol Oncol 26:127–133

    CAS  PubMed  Google Scholar 

  • Lawrence TS, Blackstock AW, McGinn C (2003) The mechanism of action of radiosensitization of conventional chemotherapeutic agents. Semin Radiat Oncol 13(1):13–21. doi:10.1053/srao.2003.50002

    Article  PubMed  Google Scholar 

  • Leipzig B (1983) Cisplatin sensitization to radiotherapy of squamous cell carcinomas of the head and neck. Am J Surg 146:462–465. doi:10.1016/0002-9610(83)90231-3

    Article  CAS  PubMed  Google Scholar 

  • Lewin F, Norell SE, Johansson H, Gustavsson P et al (1998) Smoking tobacco, oral snuff, and alcohol in the aetiology of squamous cell carcinoma of the head and neck. Cancer 82:1367–1375. doi:10.1002/(SICI)1097-0142(19980401)82:7<1367::AID-CNCR21>3.0.CO;2-3

    Article  CAS  PubMed  Google Scholar 

  • Lonn S, Ahlbom A, Christensen HC, Johansen C et al (2006) Mobile phone use and risk of parotid gland tumor. Am J Epidemiol 164:637–643. doi:10.1093/aje/kwj242

    Article  PubMed  Google Scholar 

  • Majem M, Mesia R, Mañós M, Gomez J et al (2006) Does induction chemotherapy still have a role in larynx preservation strategies? The experience of Institut Catala d’Oncologia in stage III larynx carcinoma. Laryngoscope 116:1651–1656. doi:10.1097/01.mlg.0000231736.08477.47

    Article  CAS  PubMed  Google Scholar 

  • Marchand JL, Luce D, Leclerc A, Goldberg P et al (2000) Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man-made vitreous fibers: results of a case-control study. Am J Ind Med 37:581–589. doi:10.1002/(SICI)1097-0274(200006)37:6<581::AID-AJIM2>3.0.CO;2-D

    Article  CAS  PubMed  Google Scholar 

  • Marcu L, van Doorn T, Olver I (2003) Cisplatin and radiotherapy in the treatment of locally advanced head and neck cancer. Acta Oncol 42(4):315–325. doi:10.1080/02841860310004364

    Article  CAS  PubMed  Google Scholar 

  • Medina JA, Rueda A, de Pasos AS, Contreras J et al (2006) A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol 79:34–38. doi:10.1016/j.radonc.2006.03.010

    Article  CAS  PubMed  Google Scholar 

  • Menvielle G, Luce D, Goldberg P, Bugel I et al (2004) Smoking, alcohol drinking and cancer risk for various sites of the larynx and hypopharynx. A case–control study in France. Eur J Cancer Prev 13:165–172. doi:10.1097/01.cej.0000130017.93310.76

    Google Scholar 

  • Milas L, Mason K, Liao Z, Ang K (2003) Chemoradiotherapy: emerging treatment improvement strategie. Head Neck 25:152–167. doi:10.1002/hed.10232

    Article  PubMed  Google Scholar 

  • Mould R (1993) A century of X-rays and radioactivity in medicine. Institute of Physics Publishing, Bristol

    Google Scholar 

  • Nauta JM, van Leengoed HL, Star WM, Roodenburg JL et al (1996) Photodynamic therapy of oral cancer. A review of basic mechanisms and clinical applications. Eur J Oral Sci 104:69–81. doi:10.1111/j.1600-0722.1996.tb00049.x

    CAS  Google Scholar 

  • Novacek G (2006) Plummer–Vinson syndrome. Orphanet J Rare Dis 15:1–36

    Google Scholar 

  • Nylander K, Dabelsteen E, Hall PA (2000) The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck. J Oral Pathol Med 29:413–425. doi:10.1034/j.1600-0714.2000.290901.x

    Article  CAS  PubMed  Google Scholar 

  • Olshan A, Weissler M, Pei H, Conway K (1997) p53 Mutations in head and neck cancer: new data and evaluation of mutational spectra. Cancer Epidemiol Biomarkers Prev 6:499–504

    CAS  PubMed  Google Scholar 

  • Overgaard J, Hansen HS, Specht L, Overgaard M et al (2003) Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362:933–940. doi:10.1016/S0140-6736(03)14361-9

    Article  PubMed  Google Scholar 

  • Pandor A, Eggington S, Paisley S, Tappenden P, Sutcliffe P (2006) The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation. Health Technol Assess 10:1–204

    Google Scholar 

  • Perea-Milla L, Minarro-Del Moral RM, Martinez-Garcia C, Zanetti R et al (2003) Lifestyles, environmental and phenotypic factors associated with lip cancer: a case-control study in southern Spain. Br J Cancer 88:1702–1707. doi:10.1038/sj.bjc.6600975

    Article  Google Scholar 

  • Perez-Ordoňez B, Beauchemin M, Jordan RC (2006) Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 59:445–453. doi:10.1136/jcp.2003.007641

    Article  PubMed  Google Scholar 

  • Peters LJ, Withers HR (1997) Applying radiobiological principles to combined modality treatment of head and neck cancer—the time factor. Int J Radiat Oncol Biol Phys 39:831–836. doi:10.1016/S0360-3016(97)00466-5

    CAS  PubMed  Google Scholar 

  • Robbins KT, Kumar P, Regine W et al (1997) Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience. Int J Radiat Oncol Biol Phys 38:263–271. doi:10.1016/S0360-3016(97)00092-8

    CAS  PubMed  Google Scholar 

  • Rosenquist K (2005) Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Swed Dent J Suppl 179:1–66

    PubMed  Google Scholar 

  • Sako K, Razack MS, Kalnins I (1978) Chemotherapy for advanced and recurrent squamous cell carcinoma of the head and neck with high and low dose cis-diamminedichloroplatinum. Am J Surg 136:529–533. doi:10.1016/0002-9610(78)90276-3

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Cespedes M, Esteller M, Wu L, Nawroz-Danish H et al (2000) Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res 60:892–895

    CAS  PubMed  Google Scholar 

  • Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S (1998) Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 18:4779–4786

    CAS  PubMed  Google Scholar 

  • Schantz SP, Huang Q, Shah K, Murty VV et al (2000) Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers. Carcinogenesis 21:1239–1246. doi:10.1093/carcin/21.6.1239

    Article  CAS  PubMed  Google Scholar 

  • Scher R, Esclamado R (2009) Organ and function preservation: the role of surgery as the optimal primary modality or as salvage after chemoradiation failure. Semin Radiat Oncol 19:17–23. doi:10.1016/j.semradonc.2008.09.004

    Article  PubMed  Google Scholar 

  • Schuller DE, Ozer E, Agrawal A, Grecula JC et al (2007) Multimodal intensification regimens for advanced, resectable, previously untreated squamous cell cancer of the oral cavity, oropharynx, or hypopharynx: a 12-year experience. Arch Otolaryngol Head Neck Surg 133:320–326. doi:10.1001/archotol.133.4.320

    Article  PubMed  Google Scholar 

  • Seifert E, Schadel A, Haberkorn U, Strauss LG (1992) Evaluating the effectiveness of chemotherapy in patients with head-neck tumors using positron emission tomography (PET scan). Head Neck Oncol 40:90–93

    CAS  Google Scholar 

  • Serin M, Erkal HS, Cakmak A (1999) Radiation therapy and concurrent cisplatin in management of locoregionally advanced nasopharyngeal carcinomas. Acta Oncol 38:1031–1035. doi:10.1080/028418699432310

    Article  CAS  PubMed  Google Scholar 

  • Shangina O, Brennan P, Szeszenia-Dabrowska N, Mates D et al (2006) Occupational exposure and laryngeal and hypopharyngeal cancer risk in central and eastern Europe. Am J Epidemiol 164:367–375. doi:10.1093/aje/kwj208

    Article  PubMed  Google Scholar 

  • Shirinian MH, Weber RS, Lippman SM, Dimery IW et al (1994) Laryngeal preservation by induction chemotherapy plus radiotherapy in locally advanced head and neck cancer: the M. D. Anderson Cancer Center experience. Head Neck 16:39–44. doi:10.1002/hed.2880160109

    CAS  Google Scholar 

  • Slaughter DP, Southwick HW (1953) “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer 6:963–968. doi:10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q

    CAS  Google Scholar 

  • Sturgis EM, Moore BA, Glisson BS, Kies MS et al (2005) Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series. Head Neck 27:748–756. doi:10.1002/hed.20240

    Article  PubMed  Google Scholar 

  • Vikram B, Strong EW, Shah JP et al (1984) Failure at distant sites following multimodality treatment for advanced head and neck cancer. Head Neck Surg 6:730–733. doi:10.1002/hed.2890060305

    Article  CAS  PubMed  Google Scholar 

  • Vivek RS, Baludavid M, Mohanram R, Chitra et al (2006) Concurrent chemo-irradiation using accelerated concomitant boost radiation therapy in loco-regionally advanced head and neck squamous cell carcinomas. J Cancer Res Ther 2:90–96

  • Wang Q, Wu Z, Han D, Zhang W et al (1999) Growth inhibition of human laryngeal cancer cell with the adenovirus-mediated p53 gene. Chin J Cancer Res 11:157–160

    Article  CAS  Google Scholar 

  • Yoshikawa A, Saura R, Matsubara T (1997) A mechanism of cisplatin action: antineoplastic effect through inhibition of neovascularization. Kobe J Med Sci 43:109–120

    CAS  PubMed  Google Scholar 

  • Young LS, Dawson CW, Clark D, Rupani H et al (1988) Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol 69:1051–1065. doi:10.1099/0022-1317-69-5-1051

    Article  CAS  PubMed  Google Scholar 

  • Youssef E, Lotan D, Issa JP, Wakasa K et al (2004) Hypermethylation of the retinoic acid receptor-ß 2 gene in head and neck carcinogenesis. Clin Cancer Res 10:1733–1742. doi:10.1158/1078-0432.CCR-0989-3

    Article  CAS  PubMed  Google Scholar 

  • Yuan JM, Wang XL, Xiang YB, Gao YT et al (2000) Preserved foods in relation to risk of nasopharyngeal carcinoma in Shanghai, China. Int J Cancer 85:358–363. doi:10.1002/(SICI)1097-0215(20000201)85:3<358::AID-IJC11>3.0.CO;2-E

    Article  CAS  PubMed  Google Scholar 

  • Yuen W, Man M, Lam K, Kwong Y (2002) Clinicopathological significance of p16 gene expression in the surgical treatment of head and neck squamous cell carcinomas. J Clin Pathol 55:58–60

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Adelaide, Adelaide, Australia

    Loredana G. Marcu

  2. Faculty of Science, University of Oradea, 1 Universitatii str, Oradea, Romania

    Loredana G. Marcu

  3. Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia

    E. Yeoh

Authors
  1. Loredana G. Marcu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Yeoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Loredana G. Marcu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marcu, L.G., Yeoh, E. A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment. J Cancer Res Clin Oncol 135, 1303–1314 (2009). https://doi.org/10.1007/s00432-009-0648-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-009-0648-7

Keywords

Search

Navigation