Oral cancer
Oral cancer, also known as oral cavity cancer, tongue cancer or mouth cancer, is a cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated and continues to grow. When on the lips, it commonly looks like a persistent crusting ulcer that does not heal, and slowly grows. Other symptoms may include difficult or painful swallowing, new lumps or bumps in the neck, a swelling in the mouth, or a feeling of numbness in the mouth or lips.
Risk factors include tobacco and alcohol use. Those who use both alcohol and tobacco have a 15 times greater risk of oral cancer than those who use neither. Other risk factors include betel nut chewing and sun exposure on the lip. HPV infection may play a limited role in some oral cavity cancers. Oral cancer is a subgroup of head and neck cancers. Diagnosis is made by sampling of the lesion, followed by an imaging workup which can include CT scan, MRI, PET scan to determine the local extension of the tumor, and if the disease has spread to distant parts of the body.
Oral cancer can be prevented by avoiding tobacco products, limiting alcohol use, sun protection on the lip, HPV vaccination, and avoidance of betel nut chewing. Treatments used for oral cancer can include a combination of surgery, radiation therapy, chemotherapy, or targeted therapy. The types of treatments will depend on the size, locations, and spread of the cancer taken into consideration with the general health of the person.
In 2018, oral cancer occurred globally in about 355,000 people, and resulted in 177,000 deaths. Between 1999 and 2015 in the United States, the rate of oral cancer increased 6%. Deaths from oral cancer during this time decreased 7%. Oral cancer has an overall 5 year survival rate of 70% in the United States as of 2026. This varies from 88% if diagnosed when localized, compared to 69% if it has spread to the lymph nodes in the neck, and 37% if it has spread to distant parts of the body. Survival rates also are dependent on the location of the disease in the mouth.
Signs and symptoms
The signs and symptoms of oral cancer depend on the location of the tumor but are generally thin, irregular, red and/or white patches in the mouth. The classic warning sign is a persistent rough patch with ulceration, and a raised border that is minimally painful. On the lip, the ulcer is more commonly crusting and dry, and in the pharynx it is more commonly a mass. It can also be associated with loose teeth, bleeding gums, persistent ear ache, a feeling of numbness in the lip and chin, or swelling. When the cancer extends to the oropharynx, there can also be difficulty swallowing.Causes
The main causes of oral cancer are alcohol and tobacco. The risk is especially high when a person regularly uses both. The more is consumed of either the higher the risk of developing oral cancer. Like all environmental factors, the rate at which cancer will develop is dependent on the dose, frequency and method of application of the carcinogen. Aside from tobacco and alcohol, other carcinogens for oral cancer include viruses, radiation, and UV light.Tobacco
is the greatest single cause of oral and pharyngeal cancer. Using tobacco increases the risk of oral cancer by 3 to 6 times and is responsible for around 40% of all oral cancers. Smokeless tobacco also causes oral cancer. Cigar and pipe smoking are also important risk factors.The use of electronic cigarettes may also lead to the development of head and neck cancers due to the substances like propylene glycol, glycerol, nitrosamines, and metals contained therein, which can cause damage to the airways.
Use of marijuana has currently not been shown to be associated with head and neck cancer risk.
Alcohol
Drinking alcohol is a major cause of oral cancer. It is responsible for about 20% of global oral cancer cases. The more alcohol is consumed regularly the higher the risk, but light to moderate drinking still somewhat increases the chances of getting oral cancer. The risk is especially high when both alcohol and tobacco are used.It has been controversial if the use of alcohol-based mouthwashes increases oral cancer risk. As of 2024, there is some limited evidence supporting that the use of mouthwashes containing alcohol can increase the occurrence of oral cancer in some cases. There are complex interactions between alcohol content, usage patterns, reduction of oral pathogens, poor oral hygiene, smoking, and drinking which make any broad conclusion very tenuous in the absence of rigorously controlled studies. In subgroup analyses, various combinations of smoking, drinking alcohol, poor oral hygiene, and using mouthwash several times a day for 35 years or more significantly increased risk. Although alcohol is necessary to dissolve some active antimicrobial agents, Rao et al. advise reducing the alcohol content of mouthwashes if possible.
Human papillomavirus
Infection with human papillomavirus, particularly type 16, is a cause of oropharyngeal cancer. However, its role in the genesis of oral cavity cancers is a matter of debate. A 2023 meta-analysis observed that the HPV was present 6% of all oral cavity cancer cases, however without establishing a role of this virus in the oncogenesis of these tumors. The authors even reported that some base of tongue tumors may have been misclassified as oral cavity tumors, therefore mistakenly increasing the rate of HPV-positive oral cavity cancers.Betel nut
Chewing betel quid and Areca nut-based products is known to be a strong risk factor for developing oral cancer even in the absence of tobacco. It doubles the risk of oral cancer 2.1 times and when chewed with additional tobacco in its preparation, there is an even higher risk.In India where such practices are common, oral cancer represents up to 40% of all cancers, compared to just 4% in the UK.
Stem cell transplantation
People after hematopoietic stem cell transplantation are at a higher risk for oral cancer. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in people not treated with HSCT. This effect is supposed to be owing to the continuous lifelong immune suppression and chronic oral graft-versus-host disease.This HPV16 is the same virus responsible for the vast majority of all cervical cancers and is the most common sexually transmitted infection. Risk factors for developing HPV-positive oropharyngeal cancer include multiple sexual partners, anal and oral sex and a weak immune system.
Premalignant lesions
A premalignant lesion is defined as "a benign, morphologically altered tissue that has a greater than normal risk of malignant transformation." There are several different types of premalignant lesion that occur in the mouth. Some oral cancers begin as white patches, red patches or mixed red and white patches. Other common premalignant lesions include oral submucous fibrosis and actinic cheilitis. In the Indian subcontinent oral submucous fibrosis is very common due to betel nut chewing. This condition is characterized by limited opening of mouth and burning sensation on eating of spicy food. This is a progressive lesion in which the opening of the mouth becomes progressively limited, and later on even normal eating becomes difficult.Pathophysiology
Oral squamous cell carcinoma is the end product of an unregulated proliferation of mucous basal cells. A single precursor cell is transformed into a clone consisting of many daughter cells with an accumulation of altered genes called oncogenes. What characterizes a malignant tumor over a benign one is its ability to metastasize. This ability is independent of the size or grade of the tumor. It is not just rapid growth that characterizes a cancer, but their ability to secrete enzymes, angiogeneic factors, invasion factors, growth factors and many other factors that allow it to spread.The full causal relation between alcohol consumption and the elevated risk of cancer remains unclear, but acetaldehyde plays a major role. Immediately after alcohol consumption, there are elevated levels of acetaldehyde in saliva, peaking after about 2 minutes. Acetaldehyde is produced by the oral microbiome, and also by enzymes in the oral mucosa, saliva glands, and liver. It is also naturally present in alcoholic beverages. Of these, the microbiome is the major contributor, accounting for at least half of the acetaldehyde present. Poor oral hygiene, smoking, and heavy drinking induce an increase in acetaldehyde-producing bacteria in the mouth. Many species of bacteria contribute to acetaldehyde production and their epidemiological significance is not known. The acetaldehyde reacts with oral epithelial cells, inducing DNA modifications, which can lead to mutations and cancer development. The ability to metabolize acetaldehyde in the mouth is limited, so it may remain in the saliva for hours. L-cysteine tablets may be used to decrease acetaldehyde exposure in the oral cavity.
Diagnosis
Diagnosis of oral cancer is completed for initial diagnosis, staging, and treatment planning. A complete history, and clinical examination is first completed, then a wedge of tissue is cut from the suspicious lesion for tissue diagnosis. This might be done with scalpel biopsy, punch biopsy, fine or core needle biopsy. In this procedure, the surgeon cuts all, or a piece of the tissue, to have it examined under a microscope by a pathologist. Brush biopsies are not considered accurate for the diagnosis of oral cancer. Salivary biomarkers are also being under investigation with emerging outcomes and could potentially be used as a non-invasive diagnostic tool in the future.With the first biopsy, the pathologist will provide a tissue diagnosis, and classify the cell structure. They may add additional information that can be used in staging, and treatment planning, such as the mitotic rate, the depth of invasion, and the HPV status of the tissue.
After the tissue is confirmed cancerous, other tests will be completed to:
- better assess the size of the lesion,
- look for other cancers in the upper aerodigestive tract,
- spread to the lymph nodes or
- spread to other parts of the body.
From these collective findings, taken in consideration with the health and desires of the person, the cancer team develops a plan for treatment. Since most oral cancers require surgical removal, a second set of histopathologic tests will be completed on any tumor removed to determine the prognosis, need for additional surgery, chemotherapy, radiation, immunotherapy, or other interventions.