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Oral cancer is a deadly disease affecting nearly 750,000 people worldwide with nearly 300,000 new cases diagnosed yearly and an annual mortality rate of 145,000. It is a disease of varying clinical presentation with risk based on ethnicity, geography, and habits with an underlying genetic predisposition. Oral cancer can arise de novo from normal appearing oral mucosa, but is also commonly preceded by oral mucosal lesions of varying degrees of malignant potential known collectively as oral potentially malignant disorders (OPMDs).
Given that a general dental practitioner is more likely to encounter OPMDs such as leukoplakia in daily practice compared to oral cancer, it is advisable to assess all high-risk patients clinically as part of a comprehensive head and neck cancer examination and risk assessment.
OPMDs have previously been known as premalignant lesions and include such entities as leukoplakia, erythroplakia, erythroleukoplakia, submucosa fibrosis, discoid lupus erythematosus, chronic hyperplastic candidosis, and more recently oral lichen planus. Although these conditions have differing etiologies, some better understood than others, they have a common underlying clinical presentation. They typically all appear clinically as red or white patches of the oral mucosa, with either a homogeneous consistent pattern or a nonhomogeneous pattern that is inconsistent in color, appearance, or texture from one area of the lesion to another.
Clinicians may have difficulty making accurate diagnoses for such lesions, but this has been shown not to affect outcomes, as long as clinicians can designate these lesions as homogeneous or nonhomogeneous. Keratotic, traumatic, reactive lesions have minimal potential to transform to malignancy, and they can often be diagnosed clinically and may not require biopsy or histopathological assessment. These lesions are benign and not designated as OPMD.
OPMD often are difficult to distinguish clinically. They require biopsy and histopathological assessment to offer a more definitive diagnosis, but also to investigate the presence of oral epithelial dysplasia (OED). The presence of OED on histology increases the likelihood that an OPMD may transform at some stage to oral cancer. Although there are discrepancies in the literature about the usefulness of OED in predicting oral cancer formation, and even more disagreement about the importance of OED grading in this regard, OED is still the best predictive indicator of malignant transformation.
A significant amount of work is being carried out globally to unravel molecular diagnostic, prognostic, and predictive biomarkers of oral cancer and precancer utilizing various tissue, cellular, and fluid samples. But until these have proven their clinical utility, OED on histopathological samples remains the chief indicator for treatment, clinical review, and malignant transformation.
Risk factors are easily divided into patient risk factors and lesion risk factors. Lesion risk factors are related to the clinical appearance of the lesion and should be assessed with careful clinical examination under good illumination, preferably with white light, and are significantly enhanced with magnification with the use of loupes. Common clinical features to watch out for include the clinical type, site, size, multifocality, and duration of lesions.
Lesion Risk Factors
Type—Nonhomogeneous leukoplakia, which can contain nodular and/or red areas, are associated with a 4 to 7 times greater risk of malignant transformation. Any area of chronic ulceration that does not heal within 2 weeks should also be considered a suspicious oral lesion until proven otherwise.
Site—The site of OPMD impacts on the risk of progression to malignancy and should be factored into any treatment decision. Leukoplakia that presents on the lateral border of the tongue, on the floor of mouth, or on the retromolar/soft palate region are associated with the highest risk of malignant transformation. The lateral border of the tongue has also been correlated with a higher risk of malignant transformation of dysplastic lesions compared to those affecting other intraoral subsites.
Size—The risk of progression to malignancy has been reported to be significantly higher in leukoplakia larger than 200 mm2. The same holds true for OED, with lesions greater than 200 mm2 being 3 times more likely to undergo malignant transformation compared to smaller lesions. These lesions are also more difficult to manage because of their size and resultant morbidity for patients, especially if they cross anatomic boundaries.
Multifocality—Widespread oral leukoplakia appear to exhibit a higher potential for the development of oral cancer than do localized lesions. As is the case with large lesions, multifocal lesions are more difficult to manage surgically. In the case of extensive lesions, close follow-up with regular biopsies may constitute the necessary compromise. Lesions such as oral lichen planus that typically are multifocal present a true challenge in long-term management, especially in relation to monitoring for malignant transformation, particularly given the mixed red and white appearance of these lesions in most cases.
Duration—OPMDs are by their nature chronic conditions and carry increased risk of malignant transformation, particularly in the first 5 years after diagnosis. The rate of malignant transformation may decrease after this period, but the risk does not completely disappear, with some lesions undergoing transformation even 16 years after follow-up.
Patient Risk Factors
High-risk patients for developing oral cancer include older males (older than 60 years) with a history of smoking and alcohol consumption, patients with a family history of upper aero-digestive cancer, and those with OPMD (leukoplakia, erythroplakia, oral lichen planus, discoid lupus erythematosus, chronic hyperplastic candidosis) particularly involving the lateral border of the tongue or floor of the mouth. High-risk patients for malignant transformation of oral leukoplakia (the most common OPML) include nonsmoking older females (older than 60 years) who present with a nonhomogeneous, multifocal lesion larger than 200 mm2 present on the lateral border of the tongue or floor of the mouth that has been present for less than 5 years or demonstrates oral epithelial dysplasia on biopsy.
In addition, rare inherited conditions such as xeroderma pigmentosum and Fanconi’s anemia carry an increased incidence of oral cancer. Immuno-deficiency due to the prolonged use of immunosuppressive drugs or due to an underlying HIV infection may increase risk. And, oral cancer has been reported in patients suffering from chronic Graft Versus Host Disease after haematopoietic stem cell transplantation.
Camile Farah is professor of oral oncology, dean and head of the School of Dentistry, and director of the Oral Health Centre of WA at the University of Western Australia. He has written 135 peer-reviewed publications including 16 book chapters and has attracted approximately $6 million in competitive research funding. His research interests in oral oncology span optical imaging systems (optical fluorescence imaging and narrow-band imaging), molecular genomics (next-generation sequencing), and clinical trials in early cancer detection and surgical margin delineation. He can be reached at firstname.lastname@example.org.
Disclosure: Dr. Farah has no disclosures in relation to this article.