ReviewAdvances and applications of oral cancer basic research☆
Introduction
Although the incidence of oral cavity cancer is not well documented since it is unfortunately often grouped with oropharyngeal subsites, it is thought to be the 8th most frequent cancer in the world among males and the 14th among females,1 accounting for nearly 3% of all cancer cases.2 Squamous cell carcinoma originating in the mucosal linings accounts for more than 90% of oral cavity cancers.[3], [4] The highest incidence rates occur in Pakistan, Brazil, India, and France.1 The main risk factor for oral cancer is exposure to exogenous carcinogens such as tobacco smoke and alcohol. Annually, it is estimated that 127,459 deaths are caused from oral cavity cancer worldwide, of which 96,720 occur in developing countries.2
Oral squamous cell carcinoma (OSCC) is characterized by invasive and frequent perineural growth, a considerable rate of early recurrences, and frequent lymph nodes metastasis. Often these patients develop second primary cancers in the same or adjacent anatomical region. Many patients are advanced-stage at diagnosis and incur significant morbidity and mortality due to the disease itself and the subsequent clinical management with its complications.[5], [6], [7], [8] Advances in cancer research have provided abundant new knowledge about cellular processes and molecular biology in OSCC. Our knowledge of carcinogenesis, identification of biological markers, and molecularly-targeted therapies is advancing through basic research, translational research and clinical trials, and ultimately analysis of factors specific to the individual and their tumor may result in effective “personalized medicine”.9 In the following sections, recent advances and applications of OSCC research and their impact on prevention, diagnosis, effective treatment, and improved prognosis are considered.
Section snippets
Research in risk factors for oral cancer
OSCC is a multi-causal disease with close interrelationships among etiologic factors. Risk factors include lifestyle habits (tobacco exposure and alcohol consumption), dietary factors, occupational activity, socioeconomic status, exposure to external agents, and genetic susceptibility.[10], [11], [12], [13], [14] It is probable that there are additional causative factors yet to be identified.
The deleterious effects of tobacco use and excessive alcohol consumption are well-known.[10], [15] There
Research in oral carcinogenesis and progression models
Oral carcinogenesis, like in other cancers, is a multistep process requiring the accumulation of multiple genetic alterations that modify the normal functions of proto-oncogenes and tumor suppressor genes which affect cell-cycle regulation, cellular differentiation, proliferation and death, DNA repair, and cellular immunity.[47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57] The molecular mechanisms that underlie the onset of OSCC and lead to a cellular phenotype showing increased
Optical techniques
Toluidine blue and Lugol’s iodine have been used as clinical aids to identify occult mucosal abnormalities and to demarcate the extent of a potentially malignant lesion prior to excision.[128], [129], [130], [131], [132], [133] When applied topically or as an oral rinse, toluidine blue binds to DNA and can help identify malignant lesions with reasonable accuracy.134 Furthermore, false-positive stains are too frequent for use as a valid screening tool in primary care settings.133 In addition,
Research in treatment and prognostication
The basic prognostic factors in OSCC are encompassed in the TNM classification system: tumor size (T), regional nodal involvement (N) and the presence or absence of distant metastasis (M). Although the system is imperfect152, partly because tumors with similar morphology and stage may behave differently due to their differing biological characteristics, it is widely used in treatment planning, prognostication, and comparison of outcomes.153 However, in the future, it seems likely that
Conclusions
Oral cavity cancer is an important cause of morbidity and mortality, especially in developing countries, and its prevalence may continue to rise for the foreseeable future.
Advances in our understanding of OSCC biology and clinical and laboratory technologies, offer unprecedented prospects for translational research. Implementation in clinical practice of the results of this research may enable us to improve early diagnosis, staging and prognostication, and better select appropriate treatment
Conflict of interest statement
We wish to declare that the submitted work is original and has not been submitted or published elsewhere. Also, all authors have read and approved the manuscript and agree with the current submission. Finally, there are no potential conflicts of interest.
Acknowledgments
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 06/61039-8 and CEPID/FAPESP 98/14335). Silva SD was supported by a FAPESP fellowship (06/61040-6).
References (157)
- et al.
Predictive factors for distant metastasis from oral and oropharyngeal squamous cell carcinoma
Oral Oncol
(2005) - et al.
Relationship between dental factors and risk of upper aerodigestive tract cancer
Oral Oncol
(1998) - et al.
Advances in the biology of oral cancer
Oral Oncol
(2007) Genetic variability in susceptibility and response to toxicants
Toxicol Lett
(2001)- et al.
CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma
Mutat Res
(2005) - et al.
Is oral cancer susceptibility inherited? Report of five oral cancer families
Eur J Cancer B Oral Oncol
(1996) - et al.
The genetic and molecular basis of Fanconi anemia
Mutat Res
(2009) - et al.
Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants
Blood
(2005) - et al.
Analysis of the base excision repair genes MTH1, OGG1 and MUTYH in patients with squamous oral carcinomas
Oral Oncol
(2007) - et al.
Loss of expression of DNA repair enzyme MGMT in oral leukoplakia and early oral squamous cell carcinoma. A prognostic tool?
Cancer Lett
(2007)
Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1 carcinogen metabolism, DNA repair and cell cycle control
Oral Oncol
The hallmarks of cancer
Cell
Metastasis mechanisms
Biochim Biophys Acta
Chromosomal imbalances in oral squamous cell carcinoma: examination of 31 cell lines and review of the literature
Oral Oncol
Multiple head and neck tumors frequently originate from a single preneoplastic lesion
Am J Pathol
Decision analysis and treatment threshold in a management for the N0 neck of the oral cavity carcinoma
Oral Oncol
Hunting for robust gene signature from cancer profiling data: sources of variability, different interpretations, and recent methodological developments
Cancer Lett
The ErbB/HER receptor protein-tyrosine kinases and cancer
Biochem Biophys Res Commun
Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas
Oral Oncol
Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study
Oral Oncol
The role of c-erbB receptors and ligands in head and neck squamous cell carcinoma
Oral Oncol
Significance of tyrosine kinase activity on malign transformation of ovarian tumors: a comparison between EGF-R and TGF-alpha
Acta Histochem
Oral cavity cancer in developed and in developing countries: population-based incidence
Head Neck
National Cancer Database report on cancer of the head and neck: 10-year update
Head Neck
Cancer statistics, 2008
CA Cancer J Clin
Prognostic and therapeutic potential of nuclear receptors in head and neck squamous cell carcinomas
J Oncol
Squamous cell carcinoma of the tongue: a review of 629 patients treated at a single institution
South Am J Cancer
Integration of biomarkers including molecular targeted therapies in head and neck cancer
Head Neck Pathol
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
Cancer Epidemiol Biomarkers Prev
Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications
J Dent Res
Oral cancer: prevention and detection in primary dental healthcare
Prim Dent Care
Understanding the biology of oral cancer
Med Sci Monit
World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours
Changes in smoking habit among patients with a history of oral squamous cell carcinoma (OSCC)
Med Oral Patol Oral Cir Bucal
Synergistic effects of cigarette smoke and saliva
Med Oral Patol Oral Cir Bucal
Areca nut dependence among chewers in a South Indian community who do not also use tobacco
Addiction
Smokeless tobacco: challenges, products, and cessation
Tex Dent J
The role of alcohol in oral carcinogenesis with particular reference to alcohol-containing mouthwashes
Aust Dent J
Molecular mechanisms of alcohol-mediated carcinogenesis
Nat Rev Cancer
Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck
N Engl J Med
Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study
J Natl Cancer Inst
Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus
J Natl Cancer Inst
Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States
J Clin Oncol
Population-based analysis of oral and oropharyngeal carcinoma: changing trends of histopathologic differentiation, survival and patient demographics
Laryngoscope
Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Int J Cancer
Case control study on prognostic factors in oral squamous cell carcinoma in young patients
Head Neck
Family history and the risk of oral and pharyngeal cancer
Int J Cancer
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This paper was written by members and invitees of the International Head and Neck Scientific Group (http://www.IHNSG.com).