Tumours of the oral cavity
Authors: Nalin Thakker, Keith Hunter
Journal: Periodontology 2000 (2011)

Compiling reviews on tumours of the oral cavity for a journal aimed at periodontists and general practitioners interested in periodontics was an interesting and rewarding challenge. On the face of it, this topic appears to fall outside the remit of Periodontology 2000. However, in reality, periodontists and general practitioners play a significant and a vital role in the care of patients with tumours of the oral cavity. This includes detection and diagnosis of tumours, referral to appropriate specialists for treatment, preparation of patients for treatment, management of the consequences of treatment, and rehabilitation of the patient. The depth and breadth of knowledge and the skills required to perform this role are considerable. Nonetheless, we recognize that, although this is an important part of practice, it is not the main focus of practice for most periodontists and specialist general practitioners interested in periodontics. Thus, our aim here is to reinforce the foundations of the readers’ knowledge, and, where relevant, build on it with an update on the rapidly evolving areas in understanding of tumours of the oral cavity. We have not tried to include a discussion of every type of tumour that may present in the oral cavity, but have instead focused on areas that we feel may be of interest and relevance. As befits its importance, a large proportion of the reviews are devoted to consideration of various aspects of oral squamous cell carcinoma and related potentially malignant lesions of the oral cavity. Oral squamous cell carcinoma (hereafter referred to oral cancer) is by far the most common malignant tumour of the oral cavity, accounting for over 90% of cases, and is associated with high mortality and morbidity. The review by Sloan (10) provides an illustrated description of the clinical presentation of oral cancer and potentially malignant lesions of the oral cavity, clinical examination of patients, and methods of diagnosis. Early recognition and referral for treatment are two of the most important elements of oral cancer management. As illustrated by Shaw et al. (9), this has a direct bearing on survival and morbidity. Thus, small early cancers without lymph node involvement may have 70–85% cure rates with relatively low morbidity. In contrast, late-stage cancers have an overall 5-year survival rate of <50%, and both disease and treatment cause significant morbidity, with marked compromise in function and aesthetics. The review by Johnson et al. (4) provides a comprehensive update on the epidemiology and understanding of the aetiology of oral cancer. Given its relatively low profile compared to other cancers, it is important to remember how common this cancer is, particularly in developed countries. For example, in Europe, carcinoma of the oral cavity and pharynx is more common than carcinoma of the cervix, melanoma or non-Hodgkin’s lymphoma (91,900 vs. 54,800, 84,000 and 88,400 cases, respectively, in 2008) and has a worse outcome (41,700 vs. 25,000, 20,100 and 38,200 deaths, respectively, in 2008) (2). As is well established, there is a higher incidence of oral cancer and related potentially malignant lesions in certain geographical locations, associated with a higher prevalence of high-risk activities in the populations in these locations. However, as Johnson et al. (4) also describe, there is a worrying increase in the incidence of oral cancer and/or the mortality associated with it, in some parts of the world and also in younger age groups and in certain geographical locations. There are also changes in the pattern of the disease, associated with changes in risk factors over time within selected populations. Although cancer in younger people is often suggestive of genetic predisposition, a strong cohort effect in the rising incidence in younger age groups suggests that this trend is probably due to environmental factors. The relationship between ethnicity and cancer incidence and outcome is also highlighted, and provides an example of the complex factors that determine these associations, such as ethnic or culturally related aetiological factors, and access to medical care. Aetiological factors in oral cancer and oral pre-malignant lesions are described in detail by Johnson et al. (4), and also by Warnakulasuriya (12) in the context of prevention. Of particular note is the emerging evidence for the role of human papillomavirus, diet and genetic predisposition in the aetiology of oral cancer. Human papillomavirus types 16 and 18 are now recognized as aetiological factors in a subset of head and neck cancers, particularly those arising from oropharynx, including the base of the tongue and the tonsils. Acquisition of papillomavirus is likely to occur through sexual oro-genital contact. Patients with human papillomavirus-related oral cancers tend to be younger than those with conventional oral cancers by about 3–5 years, are less likely to have history of other risk factors such as smoking, and show better survival. Oral cancer is an eminently preventable disease, with well established aetiological factors. Warnakulasuriya (12) describes and also provides evidence for the effectiveness of public health measures as well as more targeted measures that could be undertaken in dental offices or surgeries by oral health care professionals, treatment strategies for precursor lesions to prevent malignant transformation, and screening as a preventive measure. There is compelling evidence for an association between cessation of smoking and a reduced risk of oral cancer and reversal of dysplasia in potentially malignant oral lesions. Evidence from around the world suggests that community- or population-based programs are effective in reducing smoking. Thus, it is important that dental and allied professionals participate actively in public debate and decision-making in this area. More directly relevant to our practice is the mounting evidence for the effectiveness of interventions by dental professionals in smoking cessation programs. Treatment of potentially malignant oral lesions with chemopreventive agents holds promise for the future, but there is good evidence to suggest that excision of such lesions at least reduces malignant transformation rates. Although numerous new clinical and laboratory methods for diagnosis have been developed, the mainstay and gold standard for diagnosis of oral cancer and potentially malignant oral lesions remains routine histopathological examination. Woolgar & Triantafyllou (13) provide a lucid account of the correlation between pathological process, clinical features and histopathological appearance in the development of oral cancer. They detail the multiple factors involved in assessment of any lesion, and the difficulties in interpretation, and provide much needed context for clinicians in interpreting pathology reports. Although histopathological examination remains the gold standard for diagnosis of oral cancer and potentially malignant oral lesions, it is limited by one key factor, particularly for early cancers and potentially malignant lesions: the requirement for a morphologically distinct, clinically identifiable lesion that can be biopsied. Recent advances in our understanding of this disease have shown that early lesions are not always identifiable by visual examination and that affected mucosa represents a mosaic field of change in which there are patches of altered and normal cells. These factors limit the effectiveness of any screening or early diagnosis programme based on visual examination, and pose difficulties in planning treatment of early lesions. Poh et al. (8) describe promising new methods for screening and diagnosis of oral cancer, and their technical evaluation. Three reviews focus on the management of oral cancer, rehabilitation, and management of toxicities associated with treatment. Shaw et al. (9) provide an overview of management of oral cancer from diagnosis to treatment. Management of oral cancer has changed incrementally over the years, with advances in all main treatment modalities, i.e. surgery, radiotherapy and chemotherapy, with a steady improvement in survival rates. One of the most significant changes over the years has been the increasing use of multiple-modality treatments, which are proving to be much more effective in eradication or control of oral cancer than single-modality treatments. Many of the advances in surgery and other treatment modalities also offer the possibility of lower morbidity associated with treatment. Newer targeted drug treatments based on understanding of the molecular pathology of oral cancer (e.g. based on blocking the epidermal growth factor receptor that is over-expressed in cancer cells) have been modestly successful so far, but future developments in this area offer the hope of personalized therapy with treatments targeted specifically to molecular defects in individual tumours. Although there have been advances in the treatment of oral cancer, both the disease and its treatment can result in significant deficit in function and form, and have an important negative effect on the quality of life of patients with this condition. Pace-Balzan et al. (7) provide an overview of this, and describe surgical and prosthodontic reconstructive measures to restore form and function. Murphy & Gilbert (6) describe acute and chronic toxicities associated with treatment, such as mucositis, dysphagia and xerostomia, and strategies for prevention, treatment or palliation. A common theme in these two reviews is the significant role of the dental care team in management of patients at all stages, including preparation of the patient for therapy, management of toxicities, and rehabilitation. Hunter et al. (3) discuss our current understanding of the molecular pathology of oral cancer. Cancer is traditionally regarded as a disease of uncontrolled proliferation. Whilst this may be true, it is also somewhat simplistic. Cancer cells not only require the ability to proliferate indefinitely, but also require, for example, the ability to switch off apoptosis or cell suicide in response to DNA damage. In addition, cancer cells need to be able to induce new vessel growth in order to sustain growth of the tumour and retain the ability to spread. These abilities are largely driven by successive changes in genetic material of a cell. Thus, all cancers are genetic (but not necessarily familial) diseases. Hunter et al. (3) describe the principle cellular and molecular defects in oral cancer, and how an understanding of these is leading to development of molecular correlates of biological behaviour and new therapeutic strategies. The final three reviews provide expert overviews on other tumours of the oral cavity. Eveson (1) discusses salivary gland tumours, Morgan discusses (5) odontogenic tumours, and Solar & Jordan (11) discuss soft-tissue tumours and common metastases to the oral cavity. Although all of these are relatively rare tumours, the first two groups are unique to the head and neck area, and thus warrant careful consideration. The fact that they are unique to the head and neck area implies a key role for dental clinicians in diagnosis of these tumours. Eveson (1) describes the presentation and diagnosis of the more common salivary gland tumours, and highlights problems in assessing how they may behave clinically. Similarly, whilst rare, odontogenic tumours are almost all diagnosed by dental clinicians, and an update on the presentation, diagnosis and treatment of these lesions is timely (5). Least common of all are the soft tissue tumours and cancer metastasis from a distant site to the oral tissues. The key message here is to ‘expect the unexpected’. Although relatively rare, they should be considered in the differential diagnosis of appropriate lesions in the oral cavity. As the gingiva is the most common site in the oral cavity for metastases from a distant site, this should be a specific consideration in differential diagnosis of unusual gingival lesions.