Head and neck cancers are a heterogeneous group of cancers that arise from the mucosa of the larynx, pharynx, oral cavity, nasal cavity and paranasal sinuses. The majority of these epithelial malignancies are squamous cell carcinoma of the head and neck (HNSCC), and the histologic grade can vary from well-differentiated keratinizing to undifferentiated non-keratinizing.
It is generally accepted that oral cancer may arise from potentially malignant disorders.1 Oral erythroplakia has been identified as the one with the highest malignant transformation rates.
Frequently, patients with early-stage cancer present with only vague symptoms and minimal physical findings; early identification of signs and symptoms of both oral potentially premalignant disorders and oral cancer may decrease the burden associated with this disease. Therefore, the aim of this review was to provide detailed information on oral cancer and oral erythroplakia to improve dentists’ knowledge of these important diseases.
Oral and pharyngeal cancer is an important component of the worldwide burden of cancer. Oral cancer incidence has been rising over the last few decades, becoming the eighth most common cancer worldwide. The occurrence of oral cavity and oropharynx cancer is higher among males than females, and is more common in developing than developed countries. In 2008, a total of 263 861 new oral cavity cancers were diagnosed globally and about 65% of these cancers occurred in males. This accounts for approximately 2% of all new cancer diagnosed (male: 2.6%; female: 1.5%). The disease is more frequent in south-central Asia. For example, in India the age standardized incidence rate of oral cancer is reported at 12.6 per 100 000 population. However, there is also an increase in the incidence rates in Eastern and Central Europe.1,2
Survival rates for oral cancer have not shown significant improvement over the past 50 years and are among the lowest of major cancers. The 5-year and 10-year relative survival rates are 59% and 48%, respectively.3
Squamous cell carcinoma (SCC) accounts for 95% of oral cancers. The aetiology of oral cancer is multi-factorial. The most important risks factors for oral cancer are tobacco smoking and chewing, excess consumption of alcohol, betel quid chewing and being exposed to UV rays for a long period of time (lip cancer only). The combination of alcohol and tobacco use multiplies the risk. Other emerging risk factors are HPV infection, immunodeficiencies, diet and nutrition, mate drinking and socio-economic status. Unconfirmed risk factors are ethnicity and race, poor oral hygiene, dental conditions, chronic candidiasis and chronic trauma of the oral mucosa.4,5
The signs and symptoms can be a mouth sore that fails to heal or unusual bleeding, a lump, sudden tooth mobility without apparent cause or a chronic earache and a lateral lump in the neck. Most early signs are painless and are difficult to detect without a thorough head and neck examination by a dental or medical professional.
Treatment options include radiation therapy and surgery, separately or in combination and are dictated by the location and size of the lesion. Early cancers (Stage I and Stage II) of the oral cavity and lip have a better prognosis and the choice of treatment is surgery or radiation therapy (Fig 1). If regional nodes are positive, cervical node dissection is usually undertaken. In advanced disease (Stage III or greater) (Fig 2), chemotherapy is added to surgery and/or radiation.6–8 Of interest, patients who continue smoking during radiotherapy seem to have shorter survival durations and lower response rates than those who do not.9 As such, dentists should counsel their patients to quit smoking.
Potentially malignant disorders of the oral cavity
Oral potentially malignant lesion is an area of genetically and/or altered tissue that is more likely to develop cancer than a normal tissue.10 Potentially malignant disorders of the oral cavity comprise leukoplakia, erythroplakia, palatal lesions in reverse smokers, submucous fibrosis, actinic cheratosis, lichen planus, discoid lupus erythematosus, immunodeficiency in relation to cancer predisposition and some inherited cancer syndromes.11,12 The most common are leukoplakia, erythroplakia, lichen planus and submucous fibrosis.13 Even if erythroplakia is an infrequent disease, its risk of malignant progression is the highest among the oral potentially malignant disorders. Therefore, it is important to identify the correlation between oral cancer and erythroplakia and the possible implications for general dental practitioners.
The term ‘erythroplasia’ was originally used to describe a precancerous red colour that develops on the penis. According to the original 1978 WHO definition, oral erythroplakia (Fig 3) is defined as ‘any lesion of the oral mucosa that presents as bright red velvety plaques which cannot be characterized clinically or pathologically as any other recognizable condition’. Reported prevalence varies between 0.02%14 and 0.2%15 (adapted from Reichart et al.16). Clinically, it can be flat or depressed and sometimes it can be found together with leukoplakia (erythroleukoplakia); it predominately occurs in the floor of the mouth, the soft palate, the ventral tongue and the tonsillar fauces. There are usually no symptoms. However, some patients may complain of a burning sensation and/or sore. Erythroplakia shows dysplastic features and often presents as ‘carcinoma in situ’ or ‘invasive carcinoma’ at the time of biopsy.17–19 Heavy alcohol consumption and tobacco use are known to be important aetiological factors. Surgical excision is the treatment of choice though more studies are needed.15,16 The differential diagnosis includes: erythematous candidiasis, early SCC, local irritation, mucositis, lichen planus, lupus erythematosous, drug reaction and median rhomboid glossitis.20
The epithelium is often atrophic and shows lack of keratin. Sometimes hyperplasia is seen. The red colour is due to the epithelial thinness that allows the underlying microvasculature to show through.
Oral erythroplakia and progression to cancer
Using PubMed, Cochrane Library and Medline throughout June 2010, we conducted a search of the medical literature for articles on oral erythroplakia. The key search terms used were ‘oral erythroplakia’. Case reports were not included for the purpose of this analysis. The search identified 211 potentially eligible studies. After examining the abstract and full text of the articles, 10 papers were considered relevant. Papers were considered relevant if they reported on prevalence data or information on the malignant progression to invasive cancer.
Oral erythroplakia lesions were examined in 10 studies carried out from 1971 to 2007. The largest studies were carried out in the United States and India. The total number of subjects was 226 534 and 258 oral potentially malignant lesions were identified. The mean prevalence of oral erythroplakia was 0.11%. Hashibe15 reported the highest prevalence of erythroplakia (0.21%), while Lumerman21 reported the lowest (0.01%) (Table 1).
|Lumerman21||1995||USA||50 000||7||0.01||1 (14.3)|
|Shafer19||1975||USA||64 345||58||0.09||33 (56.9)|
Erythroplakia was identified through a clinical oral examination and biopsy. Sixty-two lesions developed oral cancer with a malignant transformation rate of 44.9%. However, this is just an estimate of the progression rate because of the differences across the studies and because risky behaviours (e.g. tobacco smoking, alcohol consumption) were not considered in the majority of the studies. Interestingly, most of the studies were hospital based, thus the real prevalence may differ. As such, there is an urgent need for large population based studies with an active follow-up.
Implications for clinicians
Dentists, ear, nose and throat (ENT) specialists or oral surgeons may be the first to find a red patch in the mouth of their patients. Unless a lesion has features mandating immediate biopsy, oral health professionals should eliminate the potential causes (such as minimizing frictional sources) and re-evaluate the patient in 10 to 14 days.22 If the lesion is still present, biopsy and referral to an oral medicine specialist are needed. Areas of chronic inflammation and traumatic lesions usually resolve or reduce in size within two weeks. On the contrary, any persistent mucosal lesion should be considered suspicious for oral cancer. A thorough initial evaluation of symptoms and signs is essential, together with a biopsy and long-term follow-up. Early detection of such lesions may prevent malignant transformation.23 Therefore, it is important to improve the ability of general dental practitioners to detect any relevant lesions at the earliest stage in order to interrupt the chain of progression to cancer. Indeed, general dental practitioners may be the first to see such lesions and therefore they should be able to recognize them and institute appropriate treatment such as biopsy or early referral. Also, clinicians may focus on educating their patients about oral cancer risk factors, in addition to changing risk behaviours.24 Finally, an increase in public awareness about the importance of regular oral screening may have the potential to reduce the burden of oral cancer.25,26