Oral squamous cell carcinoma (SCC) is a malignancy of surface oral epithelium origin. Chronic UV light exposure is responsible for SCC occurring on the vermilion zone of the lips, in particular the lower lip, and typically in fair-skinned individuals. In the United States, up to 80% of intraoral SCC are associated with cigarette smoking, with or without excessive alcohol use; alcohol plays a synergistic role in the development of oral SCC.
However, of increasing importance is the development of oral SCC in patients who are immunocompromised or on chronic immunosuppression such as organ transplant recipients, patients with a history of cancer of any type, and patients with a family history of cancer of any type. Other risk factors include the use of areca nut in all its variations (eg, betel paan in India). Patients who develop submucous fibrosis from chewing areca nut in its various forms are at high risk for developing SCC. More recently, human papillomavirus (HPV), in particular HPV-16, has been implicated in the development of SCC of the tonsil, oropharynx, and sometimes base of tongue. HPV-associated symptoms may have a latency of 10-30 years after oral sex exposure.
Most patients are between the ages of 50 and 70 at the time of diagnosis, although teenagers may be affected. Males are affected twice as frequently as females.
Oral SCC is generally asymptomatic in its early stages. Eventually patients will complain of tenderness, pain or numbness associated with the lesion. Depending on the location and size of the lesion, dysphagia or dysphonia may be present. Systemic signs and symptoms are usually not evident until the later stages of disease, and manifestations would include cachexia or symptoms associated with metastases.
Oral SCC generally begins as a red or white patch (erythroplakia or leukoplakia respectively) that evolves into an infiltrative ulceration or exophytic mass – over a period of months to years.
ICD10CM: C44.92 – Squamous cell carcinoma of skin, unspecified
SNOMEDCT: 307502000 – Squamous cell carcinoma of mouth
Differential Diagnosis & Pitfalls
Actinic keratosis (see actinic cheilitis) – This represents a premalignant process of the vermilion zone of the lower lip, and varying degrees of epithelial dysplasia are present in these lesions. Biopsy is often necessary to distinguish between this condition and invasive SCC.
Lichen planus consists of bilaterally symmetric reticulations and erythema.
Traumatic ulcerative granuloma presents as an indurated ulcer of the tongue that is usually present for more than 4 weeks; it has specific histopathologic features.
Leukoplakia and erythroplakia are white and red plaques, respectively, and are associated with dysplasia or carcinoma in 20% to 40%, and in 90% of cases, respectively.
Proliferative verrucous leukoplakia is a form of leukoplakia that is relentlessly progressive and often multifocal, presenting as diffuse white plaques with verrucous areas; 60% to 100% of lesions progress to carcinoma.
Nonspecific ulcer (often traumatic ulcer) – These usually have surrounding keratosis (white), the borders of which tend to blend with the adjacent mucosa, as opposed to leukoplakia, which usually has sharply demarcated borders.
Lobular capillary hemangioma (pyogenic granuloma) – This lesion usually grows more rapidly than SCC, and it is usually more sharply demarcated.
Amelanotic melanoma – This very rare intraoral lesion usually grows more rapidly than SCC but could appear clinically identical.
Specific infection (such as tuberculosis, deep fungal infection) – Systemic signs and symptoms would probably be present with these specific infections, although clinically the lesions could appear identical to SCC.
Lymphomas tend to evolve in the deeper soft tissues and appear as a diffuse swelling, but with ulceration of the overlying epithelium; they can mimic SCC.
ANCA-associated granulomatosis with polyangiitis – These present as necrotic ulcers and epistaxis, and evidence of systemic (especially pulmonary and renal) involvement is often present.
Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.