Cancers of the Oral Mucosa Clinical Presentation

Some oral squamous cell carcinomas (OSCCs) arise in apparently normal mucosa, but many are preceded by clinically obvious premalignant lesions, especially erythroplakia (red patch), leukoplakia (white patch), a speckled leukoplakia (red and white patch), or verrucous leukoplakia, and many others are associated with such lesions (especially in Southeast Asia).

Erythroplastic lesions are velvety red plaques, which in at least 85% of cases, show frank malignancy or severe dysplasia. In contrast, most white lesions are not malignant or premalignant. Speckled or verrucous leukoplakias are more likely to be premalignant. Carcinomas are seen 17 times more frequently in erythroplakias than in leukoplakias, but leukoplakias are far more common. The prevalence of malignant transformation in leukoplakias ranges from 3-33% over 10 years; homogeneous leukoplakias are only very occasionally premalignant, but speckled or verrucous leukoplakias are more likely to be premalignant.

In most cases, a biopsy and a histologic examination are required because dysplasia may precede malignant changes. The rate of malignant changes can be as high as 36% when moderate or severe dysplasia is present. Be aware that single ulcers, lumps, red patches, or white patches (particularly if they persist >3 wk) may be manifestations of malignancy.

OSCC may manifest as the following:

• A red lesion (erythroplakia)
• A granular ulcer with fissuring or raised exophytic margins
• A white or mixed white and red lesion
• A lump sometimes with abnormal supplying blood vessels
• An indurated lump/ulcer (ie, a firm infiltration beneath the mucosa)
• A nonhealing extraction socket
• A lesion fixed to deeper tissues or to overlying skin or mucosa
• Cervical lymph node enlargement, especially if hardness is present in a lymph node or fixation: Enlarged nodes in a patient with oral carcinoma may be caused by infection, reactive hyperplasia secondary to the tumor, or metastatic disease. Occasionally, a lymph node is detected in the absence of any obvious primary tumor.

These potentially malignant lesions and OSCC should be detected at an early stage; however, many oral tumors still are seen only when advanced. Diagnosis is often delayed by up to 6 months, even in developed countries, despite exhortations over the past 25 years to increase the index of suspicion. Early detection and treatment is the short-term goal because this results in considerably better survival rates. Early carcinomas may not be painful; however, later, they may cause pain and difficulty with speech and swallowing.

A systematic and thorough examination of the mouth, fauces, and cervical lymph nodes should be performed by a clinician trained in the diagnosis of oral diseases, and a general physical examination is indicated. Dental practitioners and dental care professionals are trained in the examination of the mouth.

Advanced caries, periodontal disease, or periapical lesions may need early attention, especially if radiotherapy is to be used in management of a tumor. Examine the teeth, periodontium, and entire mucosa in good lighting.

The most common sites of oral cancer include the lower lip, the lateral margin of the tongue, and the floor of the mouth; however, all areas should be scrutinized. The sump area or "coffin corner" at the posterior tongue/floor of the mouth is a common site for cancer but may be missed by cursory inspection; special care is needed to ensure close examination.

The clinical appearance of oral cancer is highly variable and includes ulcers, red or white areas, lumps, or fissures. Lesions always must be palpated after inspection to detect induration and fixation to deeper tissues.

Erythroplasia (erythroplakia) is a red and often velvety lesion, which, unlike leukoplakias, does not form a plaque but is level with or depressed below the surrounding mucosa. Of erythroplasia lesions, 75-90% prove to be carcinoma or carcinoma in situ or show severe dysplasia. Erythroplasia affects patients of either sex in their sixth and seventh decades and typically involves the floor of the mouth, the ventrum of the tongue, or the soft palate. Red oral lesions usually are more dangerous than white oral lesions.

Oral mucosal white patches usually result from increased keratinization or candidosis. Currently, the term leukoplakia is usually restricted to white patches for which a cause cannot be established; therefore, the term implies a diagnosis by exclusion (eg, lichen planus, candidiasis). The term leukoplakia is also used irrespective of the presence or absence of epithelial dysplasia. Leukoplakia is a clinical term for a persistent adherent white patch with no histologic connotation and no implied premalignant potential; keratosis is the term now commonly used. Oral carcinoma can also appear as a white patch.

• Most lip cancers manifest on the lower lip at the mucocutaneous junction as a chronic small lump, ulcer, or scabbed lesion.
• Most intraoral cancers manifest on the middle third of the lateral margins of the tongue with an erythroplastic component and, sometimes, induration.
• Late tongue cancer may manifest as an exophytic lesion, an ulcer, or an area of superficial ulceration with induration.
• A typical malignant ulcer is hard with heaped-up and often everted or rolled edges and a granular floor.
• The floor of the mouth is the second most common intraoral site for cancer and more commonly is associated with leukoplakia. Most cancer arises in the anterior floor of the mouth as an indurated mass that soon ulcerates, resulting in slurring of speech.
• Carcinomas of the alveolus or gingiva are mostly seen in the mandibular premolar and molar regions, usually as a lump (epulis) or ulcer. The underlying alveolar bone is invaded in 50% of cases, even in the absence of radiographic changes, and adjacent teeth may be loose.
• Carcinomas of the buccal mucosa are mostly seen at the commissure or in the retromolar area. Most are ulcerated lumps, and some arise in candidal leukoplakias.

Second primary tumors (SPTs) are additional primary carcinomas (synchronous tumors) present in as many as 10-15% of persons with oral carcinoma and are most commonly seen in the mouth in patients with gingival, floor of mouth, lingual, or buccal carcinoma. SPTs may also be present elsewhere in the upper aerodigestive tract.

Lymph node examination is of paramount importance, and general examination and, possibly, endoscopy, may be indicated to detect metastases or SPTs. From 30-80% of patients with oral cancer have metastases in the cervical lymph nodes at presentation. Oral cancer predominantly metastasizes locally and to regional lymph nodes, primarily in the anterior neck. Later, dissemination to the lungs, liver, or bones may occur.

Any chronic oral lesion should be regarded with suspicion, especially when found in an older patient, when lesions appear (see History), with induration, with fixation to underlying tissues, with any recent changes in appearance, with associated lymphadenopathy, or with no obvious explanation for the lesion. Examine the entire mucosa because widespread dysplastic mucosa (field change) or a second neoplasm (see Staging) may be present. Carefully record the location of suspicious lesions, preferably on a standard topographic diagram.

Tobacco and alcohol use are independent risk factors for mouth cancer and tongue cancer. Heavy tobacco smokers have a 20-fold greater risk; heavy alcohol drinkers a 5-fold greater risk and those who do both have a 50-fold greater risk. Betel-quid chewing and oral snuff are important risk factors in people from specific geographic areas (eg, betel chewing in Southeast Asia). Finally, a diet low in fresh vegetables and fruits has also been implicated in causing oral squamous cell carcinoma (OSCC), and human papillomaviruses have been implicated in oropharyngeal cancers.^[4]

• Cigarette smoking: Compared with persons who do not smoke, the risk of oral cancer in persons who smoke low/medium-tar cigarettes and high-tar cigarettes was 8.5- and 16.4-fold greater, respectively. (Note that cigarettes are classified as low/medium if the tar yield is less than 22 mg and high tar if the tar yield is greater than 22 mg). Note the image below. Early oral squamous cell carcinoma in the buccal mucosa arising from a chronic candidal leukoplakia in a person who smokes heavily. The lesion was a painless, chronic indurated lump.
• Alcohol: Growing evidence is associating increased alcohol consumption with the risk of developing OSCC.^[5] Alcoholic beverages may contain carcinogens or procarcinogens, including nitrosamine and urethane contaminants and ethanol. Ethanol is metabolized by alcohol dehydrogenase and, to some extent, by cytochrome P450 to acetaldehyde, which may be carcinogenic. The combined effects of tobacco use and alcohol consumption are found to be multiplicative. Compared with persons who do not drink and do not smoke, the risk of developing OSCC is increased 80-fold in persons with the highest levels of smoking and alcohol consumption.
• Betel and similar habits^[6] : The betel quid contains a variety of ingredients, including betel vine leaf, betel (areca) nut, catechu, and, often, slaked lime together with tobacco. Some persons chew the nut only, and others prefer paan, which includes tobacco and sometimes lime and catechu. In 1986, the International Agency for Research on Cancer has deemed betel-quid chewing an important risk factor, and the areca (betel) nut habit with or without tobacco use can cause cytogenetic changes in oral epithelium. Various other chewing habits, usually combinations that contain tobacco, are used in different cultures (eg, Qat, Shammah, Toombak). Tobacco chewing in people from parts of Asia appears to predispose to OSCC, particularly when it is started early in life and is used frequently and for prolonged periods.^{[7, 8]} Studies from India have confirmed the association between paan tobacco chewing and OSCC, particularly cancer of the buccal and labial mucosa.
• Diet: A significant protective effect of diet against oral cancer has generally been shown in persons who consume beta-carotene–rich vegetables and citric fruits.
• Oral health^[9] : A case-control study (ie, every oral cancer case prior to surgery and every control at the time of interview had a structured oral examination) from China found that wearing dentures, per se, is not a risk factor, although the risk was increased in men who wore dentures made from metal. Poor dentition, as reflected by missing teeth, emerged as a strong risk factor independent of other established risk factors.
• Mouthwash use: The effect of the alcohol in mouthwash appears to be similar to that of alcohol used for drinking, although the contribution of mouthwash use to oral cancer must be small in terms of attributable risk. This controversy continues.^{[10, 11]}
• Socioeconomic status: Behaviors that lead to social instability or social instability itself have been linked to an increased risk of oral cancer, but many other explanations may exist (eg, habits, oral health, diet, nutrition).
• Infective agents: Candida albicans and viruses, such as herpes viruses and papillomaviruses, may be implicated in some cases. Human papillomaviruses are particularly implicated in oropharyngeal cancers.^[12] HPV-related tumors tend to be seen in younger patients, in the fauces, and have usually a better prognosis.
• Other: Associations also are apparent between oral cancer and other various oral conditions (eg, oral submucous fibrosis, oral lichen planus, lupus erythematosus, dyskeratosis congenita, Fanconi anemia).