Future challenges in head and neck cancer: from the bench to the bedside?

HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a million cases [1], a 10:1 male gender predilection and country specific variability [2]. The principal risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV infection. While much progress has been made in understanding the molecular basis of cancer, the 5-year mortality of head and neck cancer has remained approximately 50%. To this date we have not been able to translate as much of our basic science knowledge into significant disease altering therapeutic strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical treatment.

[1]  G. Weinstein,et al.  Assessment of Intraoperative Safety in Transoral Robotic Surgery , 2006, The Laryngoscope.

[2]  Christopher U. Jones,et al.  Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. , 2006, The New England journal of medicine.

[3]  E. Szabo Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy , 2008, Cancer Prevention Research.

[4]  G. Weinstein,et al.  Transoral robotic surgery: radical tonsillectomy. , 2007, Archives of otolaryngology--head & neck surgery.

[5]  B. Coche-Déquéant,et al.  [Use of fast neutrons in the treatment of tumors of the salivary glands: rationale, review of the literature and experience in Orleans]. , 2000, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.

[6]  Jacques Bernier,et al.  Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. , 2004, The New England journal of medicine.

[7]  M. Latorre,et al.  Impact of comorbidity, symptoms, and patients' characteristics on the prognosis of oral carcinomas. , 2000, Archives of otolaryngology--head & neck surgery.

[8]  N. Johnson,et al.  Primary head and neck cancers in North Eastern Nigeria. , 2005, West African journal of medicine.

[9]  A. Psyrri,et al.  Human papillomavirus-related head and neck tumors: clinical and research implication , 2009, Current opinion in oncology.

[10]  P. Boyle,et al.  European School of Oncology Advisory report to the European Commission for the Europe Against Cancer Programme: oral carcinogenesis in Europe. , 1995, European journal of cancer. Part B, Oral oncology.

[11]  Massimo Bellomi,et al.  Perfusion Computed Tomography for Monitoring Induction Chemotherapy in Patients With Squamous Cell Carcinoma of the Upper Aerodigestive Tract: Correlation Between Changes in Tumor Perfusion and Tumor Volume , 2009, Journal of computer assisted tomography.

[12]  J. Debus,et al.  Intensity modulated radiotherapy (IMRT) in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes , 2006, Radiation oncology.

[13]  Philippe Lambin,et al.  Tumor perfusion rate determined noninvasively by dynamic computed tomography predicts outcome in head-and-neck cancer after radiotherapy. , 2003, International journal of radiation oncology, biology, physics.

[14]  D. Schuller,et al.  Preoperative chemotherapy in advanced resectable head and neck cancer: Final report of the southwest oncology group , 1988, The Laryngoscope.

[15]  F. Khuri,et al.  Head and neck cancer chemoprevention gets a shot in the arm. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  F. Meyskens Biomarker intermediate endpoints and cancer prevention. , 1992, Journal of the National Cancer Institute. Monographs.

[17]  R. Kerdraon,et al.  Utilisation des neutrons rapides dans le traitement des tumeurs des glandes salivaires : rationnel, revue de la littérature et expérience d'Orléans , 2000 .

[18]  E. Genden,et al.  Transoral robotic assisted free flap reconstruction , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[19]  G. Paludetti,et al.  Molecular markers in laryngeal squamous cell carcinoma: towards an integrated clinicobiological approach. , 2005, European journal of cancer.

[20]  J G Batsakis,et al.  Surgical excision margins: a pathologist's perspective. , 1999, Advances in anatomic pathology.

[21]  Loredana G. Marcu,et al.  A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment , 2009, Journal of Cancer Research and Clinical Oncology.

[22]  B. Bailey,et al.  Squamous carcinoma of the tongue: review. , 1999, The British journal of oral & maxillofacial surgery.

[23]  Gada Gaballa,et al.  Characterization of pediatric head and neck masses with diffusion-weighted MR imaging , 2008, European Radiology.

[24]  J. Pignon,et al.  Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  R. Orecchia,et al.  Particle beam radiotherapy for head and neck tumors: Radiobiological basis and clinical experience , 2006, Head & neck.

[26]  Woo Jung Lee,et al.  Transoral robotic surgery (TORS) in laryngeal and hypopharyngeal cancer. , 2009, Journal of laparoendoscopic & advanced surgical techniques. Part A.

[27]  Bradford A Moffat,et al.  A feasibility study of parametric response map analysis of diffusion-weighted magnetic resonance imaging scans of head and neck cancer patients for providing early detection of therapeutic efficacy. , 2009, Translational oncology.

[28]  C. R. Leemans,et al.  Molecular analysis of surgical margins in head and neck cancer: more than a marginal issue. , 2010, Oral oncology.

[29]  G. Studer,et al.  IMRT in Hypopharyngeal Tumors , 2006, Strahlentherapie und Onkologie.

[30]  J. Manola,et al.  TP53 mutations and survival in squamous-cell carcinoma of the head and neck. , 2007, The New England journal of medicine.

[31]  S. Leung,et al.  Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience. , 2004, International journal of radiation oncology, biology, physics.

[32]  Johan Bussink,et al.  PET-CT for response assessment and treatment adaptation in head and neck cancer. , 2010, The Lancet. Oncology.

[33]  R. Weber,et al.  Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. , 2003, The New England journal of medicine.

[34]  G. Weinstein,et al.  Transoral Robotic Surgery (TORS) for Base of Tongue Neoplasms , 2006, The Laryngoscope.

[35]  Jordi Giralt,et al.  Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. , 2010, The Lancet. Oncology.

[36]  K. Maclennan,et al.  Status of primary tumour surgical margins in squamous head and neck cancer: prognostic implications. , 2007, Current opinion in otolaryngology & head and neck surgery.

[37]  H. Dienes,et al.  Expression of p16 protein is associated with human papillomavirus status in tonsillar carcinomas and has implications on survival. , 2005, Advances in oto-rhino-laryngology.

[38]  J. Lefebvre Surgery for Laryngopharyngeal SCC in the Era of Organ Preservation , 2009, Clinical and experimental otorhinolaryngology.

[39]  H. Tsujii,et al.  Dose escalation study of carbon ion radiotherapy for locally advanced head-and-neck cancer. , 2004, International journal of radiation oncology, biology, physics.

[40]  J. Mechalakos,et al.  Concurrent chemotherapy and intensity-modulated radiotherapy for locoregionally advanced laryngeal and hypopharyngeal cancers. , 2007, International journal of radiation oncology, biology, physics.

[41]  M. Boysen,et al.  Laser surgery of T1a glottic carcinomas; significance of resection margins , 2007, European Archives of Oto-Rhino-Laryngology.

[42]  S. Leung,et al.  Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  W. Mendenhall,et al.  Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35‐year experience , 2004, Head & neck.

[44]  J. Carles,et al.  Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  D. Sidransky,et al.  Head and neck cancer. , 2001, The New England journal of medicine.

[46]  T. Pajak,et al.  Neutron vs photon irradiation of inoperable salivary gland tumors: results of an RTOG-MRC Cooperative Randomized Study. , 1988, International journal of radiation oncology, biology, physics.

[47]  John Y. K. Lee,et al.  Transoral robotic surgery of craniocervical junction and atlantoaxial spine: a cadaveric study. , 2010, Journal of neurosurgery. Spine.

[48]  Raoul Kopelman,et al.  Targeted gold nanoparticles enable molecular CT imaging of cancer. , 2008, Nano letters.

[49]  J. Woolgar,et al.  Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. , 2006, Oral oncology.

[50]  S. Mukherji,et al.  Can pretreatment CT perfusion predict response of advanced squamous cell carcinoma of the upper aerodigestive tract treated with induction chemotherapy? , 2007, AJNR. American journal of neuroradiology.

[51]  G. Weinstein,et al.  Transoral Robotic Surgery: Supraglottic Laryngectomy in a Canine Model , 2005, The Laryngoscope.

[52]  Avrum Spira,et al.  The Field of Tissue Injury in the Lung and Airway , 2008, Cancer Prevention Research.

[53]  E. Babin,et al.  Early-stage glottic cancer: oncological results and margins in laser cordectomy. , 2006, Archives of otolaryngology--head & neck surgery.

[54]  E. Ozer,et al.  Transoral Robotic Nasopharyngectomy: A Novel Approach for Nasopharyngeal Lesions , 2008, The Laryngoscope.

[55]  Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries , 2008, International journal of cancer.

[56]  A. Ostuni,et al.  Laser surgery for early glottic cancer: impact of margin status on local control and organ preservation. , 2009, Archives of otolaryngology--head & neck surgery.

[57]  B. Stewart,et al.  World Cancer Report , 2003 .

[58]  C. von Buchwald,et al.  Molecular markers in the surgical margin of oral carcinomas. , 2008, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[59]  D. Slaughter,et al.  “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin , 1953, Cancer.

[60]  M. Zelefsky,et al.  Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial Sloan-Kettering experience. , 2006, International journal of radiation oncology, biology, physics.

[61]  B. Coche-Déquéant,et al.  Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma , 2000, British Journal of Cancer.

[62]  G. Weinstein,et al.  Robotic anterior and midline skull base surgery: preclinical investigations. , 2007, International journal of radiation oncology, biology, physics.

[63]  H. K. Williams Molecular pathogenesis of oral squamous carcinoma , 2000, Molecular pathology : MP.

[64]  A. Markoe,et al.  Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. , 2007, The New England journal of medicine.

[65]  G. Weinstein,et al.  Transoral Robotic Surgery: Supraglottic Partial Laryngectomy , 2007, The Annals of otology, rhinology, and laryngology.

[66]  S. Lippman,et al.  Cancer prevention: from 1727 to milestones of the past 100 years. , 2009, Cancer research.

[67]  S. Lippman,et al.  Chemoprevention of head and neck cancer , 2010 .

[68]  T. Helliwell,et al.  Biomarkers in dysplasia of the oral cavity: a systematic review. , 2009, Oral oncology.

[69]  A. Altemani,et al.  Role of margin status in recurrence after CO2 laser endoscopic resection of early glottic cancer , 2006, Acta Oto-Laryngologica.

[70]  L. Cazares,et al.  Differential Capture of Serum Proteins for Expression Profiling and Biomarker Discovery in Pre‐ and Posttreatment Head and Neck Cancer Samples , 2008, The Laryngoscope.

[71]  A. Paccagnella,et al.  Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. , 1994, Journal of the National Cancer Institute.

[72]  M. Gapany Treatment of Early-Stage Glottic Cancer by Transoral Laser Resection , 2008 .

[73]  W. Fee Preoperative Chemotherapy in Advanced Resectable Head and Neck Cancer: Final Report of the Southwest Oncology Group , 1989 .

[74]  G. Shah,et al.  New directions in head and neck imaging , 2008, Journal of surgical oncology.

[75]  K. Olsen,et al.  Transoral robotic surgery for oropharyngeal squamous cell carcinoma: A prospective study of feasibility and functional outcomes , 2009, The Laryngoscope.

[76]  S. Bosari,et al.  Biomolecular Markers in Cancer of the Tongue , 2009, Journal of oncology.

[77]  A. Ostuni,et al.  Compartmental surgery in tongue tumours: description of a new surgical technique. , 2009, Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale.

[78]  G. Weinstein,et al.  Multivariate Predictors of Occult Neck Metastasis in Early Oral Tongue Cancer , 2003, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[79]  L. Dawson,et al.  Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study. , 2003, International journal of radiation oncology, biology, physics.

[80]  K. Stelzer,et al.  Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. , 2000, International journal of radiation oncology, biology, physics.

[81]  R. Engenhart,et al.  European results in neutron therapy of malignant salivary gland tumors. , 1996, Bulletin du cancer. Radiotherapie : journal de la Societe francaise du cancer : organe de la societe francaise de radiotherapie oncologique.

[82]  J. Bourhis,et al.  Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data , 2000, The Lancet.

[83]  J. Pignon,et al.  Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta analysis of chemotherapy on head and neck cancer , 2001 .

[84]  G. Almadori,et al.  Multistep laryngeal carcinogenesis helps our understanding of the field cancerisation phenomenon: a review. , 2004, European journal of cancer.

[85]  E. Weiderpass,et al.  Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries , 2008, International journal of cancer.

[86]  R. Strausberg,et al.  Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis. , 2003, Oral oncology.

[87]  A. Bozec,et al.  Emerging molecular targeted therapies in the treatment of head and neck cancer , 2009, Expert opinion on emerging drugs.

[88]  G. Weinstein,et al.  Robotic skull base surgery: preclinical investigations to human clinical application. , 2007, Archives of otolaryngology--head & neck surgery.

[89]  L. Wirth,et al.  Cetuximab and radiotherapy for head and neck cancer. , 2006, The New England journal of medicine.

[90]  T. Gorlia,et al.  Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. , 2007, The New England journal of medicine.

[91]  R. Ralhan,et al.  Significance of promoter hypermethylation of p16 gene for margin assessment in carcinoma tongue , 2009, Head & neck.

[92]  Edward S. Kim,et al.  Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[93]  J. Myers,et al.  Squamous cell carcinoma of the tongue in young adults: Increasing incidence and factors that predict treatment outcomes , 2000, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[94]  H. Thoeny,et al.  Laryngeal and hypopharyngeal carcinomas after (chemo)radiotherapy: a diagnostic dilemma , 2008, Current opinion in otolaryngology & head and neck surgery.

[95]  David Sidransky,et al.  Emerging molecular markers of cancer , 2002, Nature Reviews Cancer.

[96]  M. Keefe,et al.  Transoral Robotic Surgery (TORS): Glottic Microsurgery in a Canine Model , 2007 .

[97]  M. Gapany Impact of Re-resection for Inadequate Margins on the Prognosis of Upper Aerodigestive Tract Cancer Treated by Laser Microsurgery , 2008 .

[98]  M. van Glabbeke,et al.  Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501) , 2005, Head & neck.

[99]  G. Weinstein,et al.  Diffusion-Weighted Magnetic Resonance Imaging for Predicting and Detecting Early Response to Chemoradiation Therapy of Squamous Cell Carcinomas of the Head and Neck , 2009, Clinical Cancer Research.

[100]  K. Kinzler,et al.  Cancer genes and the pathways they control , 2004, Nature Medicine.

[101]  A. Azzarelli Surgery in soft tissue sarcomas. , 1993, European journal of cancer.

[102]  V. Chong,et al.  Oral cavity cancer , 2005, Cancer imaging : the official publication of the International Cancer Imaging Society.

[103]  C. Tseng,et al.  Tumor cell expression of podoplanin correlates with nodal metastasis in esophageal squamous cell carcinoma. , 2009, Histology and histopathology.

[104]  Margie Hunt,et al.  Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: the Memorial Sloan-Kettering Cancer Center experience. , 2006, International journal of radiation oncology, biology, physics.

[105]  J. Sham,et al.  Intensity‐modulated radiotherapy for early‐stage nasopharyngeal carcinoma , 2004, Cancer.

[106]  M. Varvares,et al.  Surgical margin determination in head and neck oncology: Current clinical practice. The results of an International American Head and Neck Society Member Survey , 2005, Head & neck.

[107]  M. Strome,et al.  Transoral Robot‐Assisted CO2 Laser Supraglottic Laryngectomy: Experimental and Clinical Data , 2007, The Laryngoscope.

[108]  J. Bernier,et al.  Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck? , 2007, European journal of cancer.

[109]  S. Mukherji,et al.  Correlation between initial and early follow-up CT perfusion parameters with endoscopic tumor response in patients with advanced squamous cell carcinomas of the oropharynx treated with organ-preservation therapy. , 2006, AJNR. American journal of neuroradiology.

[110]  Sandra Nuyts,et al.  Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after (chemo)radiotherapy: correlation between radiologic and histopathologic findings. , 2007, International journal of radiation oncology, biology, physics.

[111]  K. Tsai,et al.  Chronic exposure to heavy metals and risk of oral cancer in Taiwanese males. , 2010, Oral oncology.

[112]  G. Ogden,et al.  Incidence of oral and oropharyngeal cancer in United Kingdom (1990-1999) -- recent trends and regional variation. , 2006, Oral oncology.

[113]  T. Palmer,et al.  15-Year review of laryngeal and oral dysplasias and progression to invasive carcinoma , 2010, European Archives of Oto-Rhino-Laryngology.

[114]  Diane D. Liu,et al.  Cyclin D1 and Cancer Development in Laryngeal Premalignancy Patients , 2009, Cancer Prevention Research.

[115]  K. Harrington,et al.  Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up. , 2009, Cancer treatment reviews.

[116]  A. Giaccia,et al.  Therapeutic exploitation of the physiological and molecular genetic alterations in head and neck cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[117]  E. Rosenthal,et al.  Functional Outcomes after Transoral Robotic Surgery for Head and Neck Cancer , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[118]  L Michaels,et al.  The uncertainty of the surgical margin in the treatment of head and neck cancer. , 2007, Oral oncology.

[119]  A. Olshan,et al.  Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. , 2009, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[120]  H. zur Hausen,et al.  Papillomaviruses in the causation of human cancers - a brief historical account. , 2009, Virology.

[121]  G. Weinstein,et al.  Transoral Robotic Free Flap Reconstruction of Oropharyngeal Defects: A Preclinical Investigation , 2010, Plastic and reconstructive surgery.

[122]  C. Scully,et al.  Chemoprevention and oral cancer--(more) trials and (more) tribulations. , 1995, European journal of cancer. Part B, Oral oncology.

[123]  J. Lefebvre Laryngeal preservation in head and neck cancer: multidisciplinary approach. , 2006, The Lancet. Oncology.

[124]  Quynh-Thu Le,et al.  New developments in radiation therapy for head and neck cancer: intensity-modulated radiation therapy and hypoxia targeting. , 2008, Seminars in oncology.

[125]  S. Mukherji,et al.  Differentiation of Benign and Malignant Pathology in the Head and Neck Using 3T Apparent Diffusion Coefficient Values: Early Experience , 2008, American Journal of Neuroradiology.