Oral cancer

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 (back of the throat), there can also be difficulty swallowing. ==Causes==

The main causes of oral cancer are alcohol and tobacco (smoked or chewed). 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 (the substance that is causing the cancer). Aside from tobacco and alcohol, other carcinogens for oral cancer include viruses (particularly HPV 16 and 18), radiation, and UV light. Smokeless tobacco (including chewing tobacco, snuff, snus) 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. 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 (HPV), particularly type 16, is a cause of oropharyngeal cancer (tonsils, base of tongue). However, its role in the genesis of oral cavity cancers is a matter of debate. Betel nut Chewing betel quid (paan) 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 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 (HSCT) 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. Premalignant lesions (white patch) on the left tongue. Proven to be severe dysplasia on biopsy A premalignant (or precancerous) 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 (leukoplakia), red patches (erythroplakia) or mixed red and white patches (erythroleukoplakia or "speckled leukoplakia"). 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 (often seemingly slow growing cancers like the adenoid cystic carcinoma can metastasis widely). 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. 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 (1) initial diagnosis, (2) staging, and (3) 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 (e.g. squamous cell carcinoma), 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 (CT scan, MRI or PET scan with 18F-fluorodeoxyglucose (FDG)), 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. Classification Oral cancer is a subgroup of head and neck cancers which includes those of the oropharynx, larynx, nasal cavity and paranasal sinuses, salivary glands, and thyroid gland. Oral melanoma, while part of head and neck cancers is considered separately. It is one of the factors affecting both the prognosis and the potential treatment of oral cancer. TMN evaluation allows the person to be classified into a prognostic staging group; ==Screening==

The gold standard for diagnosing oral cancer is biopsy with histopathological examination. A biopsy is invasive and unsuitable for large-scale screening. Dentists serve as primary gatekeepers for oral cancer screening and referral for biopsy or treatment but often lack sufficient training to perform this effectively. Screening accuracy in dental practice remains low. In a 2008 statistic, over half of oral cancers were found after spreading to the lymph nodes or other areas. Screening risks include false positives, unnecessary biopsies, and financial cost. Artificial intelligence shows potential to assist in diagnosing and managing oral diseases with high precision. Some researchers describe AI as essential to improving oral cancer detection and treatment. Reviews report AI imaging systems reaching about 89.9% sensitivity, 89.2% specificity, and 89.5% negative predictive value, similar to expert human performance. Implementation challenges remain, and there is no consensus on the most effective AI method. Studies have used optical coherence tomography, autofluorescence spectroscopy, and thermal imaging, showing high variation in approach. Micronuclei assays may help detect early malignant changes and improve survival outcomes. AI applications in histological diagnosis may also reduce diagnostic costs. Other screening methods, including toluidine blue staining and fluorescence imaging, have not shown enough evidence for routine use, A 2013 Cochrane review found that visual oral examination reduced mortality in high-risk individuals and improved survival in the general population, based on one study. The review has not been updated due to a lack of new randomized controlled trials. The World Health Organization in 2023 recommended screening only for high-risk groups, including users of tobacco, areca nut, alcohol, or combinations of these. The organization noted that positive results from some screening studies may be overstated or not generalizable. Similar concerns about publication bias and overestimated diagnostic performance have been stated for AI studies. ==Management==

(feeding tube in nose)Oral cancer (squamous cell carcinoma) is usually treated with surgery alone, or in combination with adjunctive therapy, including radiation, with or without chemotherapy. Management of the neck Spread of cancer from the oral cavity to the lymph nodes of the neck has a significant effect on survival. Between 60 and 70% of people with early stage oral cancer will have no lymph node involvement of the neck clinically, but 20–30% of those people (or up to 20% of all those affected) will have clinically undetectable spread of cancer to the lymph nodes of the neck (called occult disease). The management of the neck is crucial, since spread to it reduces the chance of survival by 50%. If there is evidence of lymph node involvement of the neck, during the diagnostic phase, then a modified radical neck dissection is generally performed. Where the neck lymph nodes have no evidence of involvement clinically, but the oral cavity lesion is high risk for spread (e.g. T2 or above lesions), then a neck dissection of the lymph nodes above the level of the omohyoid muscle may be completed. T1 lesions that are 4 mm or greater in thickness have a significant risk of spread to neck nodes. When disease if found in the nodes after removal (but not seen clinically) the recurrence rates is 10–24%. If post-operative radiation is added, the failure rate is 0–15%. When lymph nodes are clinically found during the diagnosis phase, and radiation is added post-operative, disease control is >80%. Radiotherapy and chemotherapy Chemotherapy and radiotherapy are most often used, as an adjunct to surgery, to control oral cancer that is greater than stage 1, or has spread to either regional lymph nodes or other parts of the body. Monoclonal antibody therapy (with agents such as cetuximab) have been shown to be effective in the treatment of squamous cell head and neck cancers, and are likely to have an increasing role in the future management of this condition when used in conjunction with other established treatment modalities, although it is not a replacement for chemotherapy in head and neck cancers. Rehabilitation Following treatment, rehabilitation may be necessary to improve movement, chewing, swallowing, and speech. Speech and language pathologists may be involved at this stage. Treatment of oral cancer will usually be by a multidisciplinary team, with treatment professionals from the realms of radiation, surgery, chemotherapy, nutrition, dentistry, and even psychology all possibly involved with diagnosis, treatment, rehabilitation, and care. Due to the location of oral cancer, there may be a period where the person requires a tracheotomy and feeding tube. ==Prognosis==

Survival rates for oral cancer depend on the precise site and the stage of the cancer at diagnosis. Overall, 2011 data from the SEER database shows that survival is around 57% at five years when all stages of initial diagnosis, all genders, all ethnicities, all age groups, and all treatment modalities are considered. Survival rates for stage 1 cancers are approximately 90%, hence the emphasis on early detection to increase survival outcome for people. Similar survival rates are reported from other countries, such as Germany. ==Epidemiology==

Globally, it newly occurred in about 355,000 people and resulted in 177,000 deaths in 2018. Oral cancer occurs more often in people from lower and middle income countries. As of 2025, it is the fastest growing cancer among young men in Western countries, and is in most cases related to HPV, the most common sexually transmitted infection globally. As of 2025, oropharyngeal cancers caused by the virus have more than doubled in the last 30 years, especially in males. Europe Europe places second-highest after Southeast Asia among all continents for age-standardised rate (ASR) specific to oral and oropharyngeal cancer. It is estimated that there were 61,400 cases of oral and lip cancer within Europe in 2012. Hungary recorded the highest number of mortality and morbidity due to oral and pharyngeal cancer among all European countries while Cyprus reported the lowest numbers  United Kingdom British Cancer Research found 2,386 deaths due to oral cancer in 2014; while most oral cancer cases are diagnosed in older adults between 50 and 74 years old, this condition can affect the young as well; 6% of people affected by oral cancer are under 45 years of age. The United Kingdom is 16th-lowest for males and 11th-highest for females for oral cancer incidence among Europe. Additionally, there is a regional variability within the United Kingdom, with Scotland and northern England having higher rates than southern England. The same analysis applies to lifetime risk of developing oral cancer, as in Scotland it is 1.84% in males and 0.74% in females, higher than the rest of the UK, being 1.06% and 0.48%, respectively. Oral cancer is the sixteenth most-common cancer in the United Kingdom (around 6,800 people were diagnosed with oral cancer in the United Kingdom in 2011), and it is the 19th most-common cause of cancer death (around 2,100 people died from the disease in 2012). The high incidence rate of oral and pharyngeal cancer in Denmark could be attributed to their higher alcohol intake than citizens of other Scandinavian countries and low intake of fruits and vegetables in general. Eastern Europe Hungary (23.3), Slovakia (16.4), and Romania (15.5) reported the highest incidences of oral and pharyngeal cancer. Cigarette smoking, excessive alcohol consumption, inequalities in the care received by people with cancer, and gender-specific systemic risk factors have been determined as the leading causes for the high morbidity and mortality rates in Hungary. Western Europe The incidence rates of oral cancer in western Europe found France, Germany and Belgium to be highest. The ASRs (per 100,000) were 15.0, 14.6, and 14.1, respectively. When filtered by gender category, the same countries rank top 3 for male, however, in different order of Belgium (21.9), Germany (23.1), and France (23.1). France, Belgium, and the Netherlands rank highest for females, with ASRs 7.6, 7.0, and 7.0, respectively. In 2022, close to 54,000 Americans are projected to be diagnosed with oral or oropharyngeal cancer. 66% of the time, these will be found as late stage three and four disease. It will cause over 8,000 deaths. Of those newly diagnosed, only slightly more than half will be alive in five years. Similar survival estimates are reported from other countries. For example, five-year relative survival for oral cavity cancer in Germany is about 55%. South America The ASIR across all geographic regions of South America as of 2012 sits at 3.8 per 100,000 population where approximately 6,046 deaths have occurred due to lip and oral cavity cancer, where the age-standardized mortality rate remains at 1.4. In Brazil, however, lip and oral cavity cancer is the 7th most common cancer, with an estimated 6,930 new cases diagnosed in the year 2012. This number is rising and has an overall higher ASIR at 7.2 per 100,000 population whereby an approx 3000 deaths have occurred According to GLOBOCAN 2012, the estimated age-standardised rates of cancer incidence and mortality was higher in males than females. However, in some areas, specifically South East Asia, similar rates were recorded for both genders. India Oral cancer is the third-most-common form of cancer in India with over 77 000 new cases diagnosed in 2012 (2.3:1 male to female ratio). Studies estimate over five deaths per hour. One of the reasons behind such high incidence might be popularity of betel and areca nuts, which are considered to be risk factors for development of oral cavity cancers. Africa There is limited data for the prevalence of oral cancer in Africa. The following rates describe the number of new cases (for incidence rates) or deaths (for mortality rates) per 100 000 individuals per year. The mortality rate is significantly lower than the incidence rate at 1.0 for both sexes. The rate is higher in males at 1.4 and lower in females at 0.6. Table 1 provides age-standardised incidence and mortality rates for oral cancer based on the location in the mouth. The location 'other mouth' refers to the buccal mucosa, the vestibule and other unspecified parts of the mouth. The data suggests lip cancer has the highest incidence rate while gingival cancer has the lowest rate overall. In terms of mortality rates, oropharyngeal cancer has the highest rate in males and tongue cancer has the highest rate in females. Lip, palatal and gingival cancer have the lowest mortality rates overall. ==Other animals==

Oral cancers are the fourth most common type seen in other animals in veterinary medicine, with older animals having higher chances of developing it. Dogs that are a breed that is at higher risk of developing oral cancer are more susceptible. Tumors that are found early in development can be removed by surgery, however some cases involve removing a part of the jaw. Chemotherapy is used following surgeries or to remove a tumor that cannot be accessed. Tumors that are caught when the cancer has already spread to other places of the body will result in the dog living for only 6-12 more months. The most common type of oral cancer seen in cats is squamous cell carcinoma. Due to tumors developing in hidden spots such as beneath the tongue, when the tumors in the cats mouth are caught it is often untreatable. Risk factors include secondhand smoke, as the smoke settles on the fur which is ingested when cats groom, and potentially the over consumption of canned food and use of flea collars. == References ==