|Other names||Cancer of the lip, oral cavity and pharynx, mouth cancer, cancer or the lips, oral cavity and pharynx|
|Oral cancer on the side of the tongue, a common site along with the floor of the mouth|
|Specialty||Oncology, ENT surgery, oral and maxillofacial surgery|
|Symptoms||Persistent rough white or red patch in the mouth lasting longer than 2 weeks, ulceration, lumps/bumps in the neck, pain, loose teeth, difficulty swallowing|
|Risk factors||Smoking, alcohol, HPV infection, sun exposure (lower lip)|
|Diagnostic method||Tissue biopsy, CT scan, MRI|
|Differential diagnosis||Non-squamous cell carcinoma oral cancer, salivary gland tumors, benign mucosal disease|
|Prevention||Frequent screening at the dentist, HPV vaccination, limit alcohol <2 drinks per day, avoid tobacco, HPV vaccination|
|Treatment||Surgery, radiation, chemotherapy|
|Prognosis||Five-year survival 63%, highly dependent on site of tumor and spread|
|Frequency||11.3 per 100,000 (US)|
|Deaths||2.5 per 100,000 (US); 146,000 (2015)|
Oral cancer, also known as mouth cancer , is cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless white patch, that thickens, develops red patches, an ulcer, 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. With both tobacco and drinking alcohol the risk of oral cancer is 15 times greater. Other risk factors include HPV infection, chewing paan, and sun exposure on the lower lip. Oral cancer is a subgroup of head and neck cancers. Diagnosis is made by biopsy of the concerning area, followed by investigation with CT scan, MRI, PET, and examination to determine if it has spread to distant parts of the body.
Oral cancer can be prevented by avoiding tobacco products, limiting alcohol use, sun protection on the lower lip, HPV vaccination, and avoidance of paan. Treatments used for oral cancer can include a combination of surgery (to remove the tumor and regional lymph nodes), 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 patient.
Between 1999 and 2015 in the United States rate of oral cancer increased 6% (from 10.9 to 11.6 per 100,000). Even though smoking cessation campaigns have decreased the rate of tobacco induced tumors, the rate of HPV related cancers has offset the gains. Deaths from oral cancer during this time deceased 7% (from 2.7 to 2.5 per 100,000). Oral cancer has an overall survival rate of 63% but varies widely depending on when treatment is started. If treated early in the disease, oral cancer has an 84% 5-year survival rate, compared to 65% if it has spread to the lymph nodes in the neck, and 39% if it has spread to distant parts of the body. Survival rates also are highly dependent on the location of the disease in the mouth.
- 1 Signs and symptoms
- 2 Causes
- 3 Pathophysiology
- 4 Diagnosis
- 5 Management
- 6 Prognosis
- 7 Epidemiology
- 8 References
- 9 External links
Signs and symptoms
The signs and symptoms of oral cancer depend on the location of the tumor. 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 a white patch, loose teeth, bleeding gums, persistent ear ache, a feeling of numbness in the lip and chin or swelling. In the case of pharyngeal cancer there can also be difficulty or painful swallowing, and an altered voice. Typically the lesions have very little pain until they become larger and then are associated with a burning sensation. As the lesion spreads to the lymph nodes of the neck, a painless hard mass will develop, and if it spreads elsewhere in the body general aches can develop most often due to bone metastasis.
Oral squamous cell carcinoma is a disease of environmental factors, the greatest of which is tobacco. Like all environmental factors, the rate at which cancer will develops is dependent on the dose, frequency and method of application of the carcinogen (the substance that is causing the cancer). Aside from cigarette smoking, other carcinogens for oral cancer include alcohol, viruses (particularly HPV 16 and 18), radiation, and UV light.
Tobacco is known to be a multi-organ carcinogen, that has a synergistic interaction with alcohol to cause cancers of the mouth and pharynx by directly damaging cellular DNA. Tobacco is estimated to increase the risk of oral cancer by 3.4-6.8 and is responsible for approximately 40% of all oral cancers.
Some studies in Australia, Brazil and Germany pointed to alcohol-containing mouthwashes as also being potential causes. The claim was that constant exposure to these alcohol-containing rinses, even in the absence of smoking and drinking, leads to significant increases in the development of oral cancer. However, studies conducted in 1985, 1995, and 2003 summarize that alcohol-containing mouth rinses are not associated with oral cancer. In a March 2009 brief, the American Dental Association said "the available evidence does not support a connection between oral cancer and alcohol-containing mouthrinse". A 2008 study suggests that acetaldehyde (a breakdown product of alcohol) is implicated in oral cancer, but this study specifically focused on abusers of alcohol and made no reference to mouthwash. Any connection between oral cancer and mouthwash is tenuous without further investigation.
Infection with human papillomavirus (HPV), particularly type 16 (there are over 180 types), is a known risk factor and independent causative factor for oral cancer. A fast-growing segment of those diagnosed does not present with the historic stereotypical demographics. Historically that has been people over 50, blacks over whites 2 to 1, males over females 3 to 1, and 75% of the time people who have used tobacco products or are heavy users of alcohol. This new and rapidly growing sub population between 30 and 50 years old, is predominantly nonsmoking, white, and males slightly outnumber females. Recent research from multiple peer-reviewed journal articles indicates that HPV16 is the primary risk factor in this new population of oral cancer victims. HPV16 (along with HPV18) is the same virus responsible for the vast majority of all cervical cancers and is the most common sexually transmitted infection in the US. Oral cancer in this group tends to favor the tonsil and tonsillar pillars, base of the tongue, and the oropharynx. Recent data suggest that individuals that come to the disease from this particular cause have a significant survival advantage, as the disease responds better to radiation treatments than tobacco caused disease.
Chewing betel, paan and Areca is known to be a strong risk factor for developing oral cancer even in the absence of tobacco. It increases the rate of oral cancer 2.1 times, through a variety of genetic and related effects through local irritation of the mucous membrane cells, particularly from the areca nut and slaked lime. 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
Patients after hematopoietic stem cell transplantation (HSCT) are at a higher risk for oral squamous cell carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients. This effect is supposed to be owing to the continuous lifelong immune suppression and chronic oral graft-versus-host disease.
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. It occurs almost exclusively in India and Indian communities living abroad.
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.
Early diagnosis of oral cancer patients would decrease mortality and help to improve treatment. Oral surgeons and dentists can diagnose these patients in the early stages. Health providers, dentists, and oral surgeons shall have high knowledge and awareness that would help them to provide better diagnosis for oral cancer patients. An examination of the mouth by the health care provider, dentist, oral surgeons shows a visible and/or palpable (can be felt) lesion of the lip, tongue, or other mouth area. The lateral/ventral sides of the tongue are the most common sites for intraoral SCC. As the tumor enlarges, it may become an ulcer and bleed. Speech/talking difficulties, chewing problems, or swallowing difficulties may develop. A feeding tube is often necessary to maintain adequate nutrition. This can sometimes become permanent as eating difficulties can include the inability to swallow even a sip of water. The doctor can order some special investigations which may include a chest x-ray, CT or MRI scans, and tissue biopsy.
While a dentist, physician or other health professional may suspect a particular lesion is malignant, there is no way to tell by looking alone - since benign and malignant lesions may look identical to the eye. A non-invasive brush biopsy (BrushTest) can be performed to rule out the presence of dysplasia (pre-cancer) and cancer on areas of the mouth that exhibit an unexplained color variation or lesion. The only definitive method for determining if cancerous or precancerous cells are present is through biopsy and microscopic evaluation of the cells in the removed sample. A tissue biopsy, whether of the tongue or other oral tissues and microscopic examination of the lesion confirm the diagnosis of oral cancer or precancer.
The US Preventive Services Task Force (USPSTF) in 2013 stated evidence was insufficient to determine the balance of benefits and harms of screening for oral cancer in adults without symptoms by primary care providers. The American Academy of Family Physicians comes to similar conclusions while the American Cancer Society recommends that adults over 20 years who have periodic health examinations should have the oral cavity examined for cancer. The American Dental Association recommends that providers remain alert for signs of cancer during routine examinations.
There are a variety of screening devices, however, there is no evidence that routine use of these devices in general dental practice is helpful. However, there are compelling reasons to be concerned about the risk of harm this device may cause if routinely used in general practice. Such harms include false positives, unnecessary surgical biopsies and a financial burden.
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. Other cancers can occur in the mouth (such as bone cancer, lymphoma, or metastatic cancers from distant sites) but are also considered separately from oral cancers.
Oral cancer staging is an assessment of the degree of spread of the cancer from its original source. It is one of the factors affecting both the prognosis and the potential treatment of oral cancer.
The evaluation of squamous cell carcinoma of the mouth and pharynx staging uses the TNM classification (tumor, node, metastasis). This is based on the size of the primary tumor, lymph node involvement, and distant metastasis.
TMN evaluation allows the patient to be classified into a prognostic staging group;
|When T is...||And N is...||And M is...||Then the stage group is...|
|Any T||Any N||M1||IVC|
Surgical excision (removal) of the tumor is usually recommended if the tumor is small enough, and if surgery is likely to result in a functionally satisfactory result. Radiation therapy with or without chemotherapy is often used in conjunction with surgery, or as the definitive radical treatment, especially if the tumour is inoperable. Surgeries for oral cancers include:
- Maxillectomy (can be done with or without orbital exenteration)
- Mandibulectomy (removal of the mandible or lower jaw or part of it)
- Glossectomy (tongue removal, can be total, hemi or partial). When glossectomy is performed for smaller tumors (< 4 cm), the adequacy of resection (margin status) is best assessed from the resected specimen itself. The status of the margin (positive/tumor cut through versus negative/clear margin) obtained from the glossectomy specimen appears to be of prognostic value, while the status of the margin sampled from the post-glossectomy defect is not. The method of margin sampling appears to correlate with local recurrence: preference for tumor bed/defect margins may be associated with worse local control.
- Radical neck dissection
- Mohs surgery or CCPDMA
- Combinational, e.g. glossectomy and laryngectomy done together
- Feeding tube to sustain nutrition
Owing to the vital nature of the structures in the head and neck area, surgery for larger cancers is technically demanding. Reconstructive surgery may be required to give an acceptable cosmetic and functional result. Bone grafts and surgical flaps such as the radial forearm flap are used to help rebuild the structures removed during excision of the cancer. An oral prosthesis may also be required. Most oral cancer patients depend on a feeding tube for their hydration and nutrition. Some will also get a port for the chemo to be delivered. Many oral cancer patients are disfigured and suffer from many long term after effects. The after effects often include fatigue, speech problems, trouble maintaining weight, thyroid issues, swallowing difficulties, inability to swallow, memory loss, weakness, dizziness, high frequency hearing loss and sinus damage.
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 patients. Similar survival rates are reported from other countries such as Germany.
Chemotherapy is useful in oral cancers when used in combination with other treatment modalities such as radiation therapy. It is not used alone as a monotherapy. When a cure is unlikely, it can also be used to extend life and can be considered palliative but not curative care. Biological agents such as Cetuximab have recently 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. Likewise, molecularly targeted therapies and immunotherapies maybe be effective for the treatment of oral and oropharyngeal cancers. Adding epidermal growth factor receptor monoclonal antibody (EGFR mAb) to standard treatment may increase survival, keeping the cancer limited to that area of the body and may decrease reappearance of the cancer.
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 patient care.
- Postoperative disfigurement of the face, head and neck
- Complications of radiation therapy, including dry mouth and difficulty swallowing
- Other metastasis (spread) of the cancer
- Significant weight loss
Prognosis depends on stage and overall health. Grading of the invasive front of the tumor is a very important prognostic parameter.
In 2013 oral cancer resulted in 135,000 deaths, up from 84,000 deaths in 1990. Oral cancer occurs more often in people from the lower end of the socioeconomic scale. In the US oral cancer accounts for about 8 percent of all malignant growths. Men are affected twice as often as women, particularly men older than 40/60.
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 
British Cancer Research found 2,386 deaths due to oral cancer in 2014; other studies show this is particularly within the elder population category; only 6% of people affected by oral cancer are under 45. The UK is 16th-lowest for males and 11th-highest for females for oral cancer incidence among Europe. Additionally, there is a regional variability within the UK, 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 UK (around 6,800 people were diagnosed with oral cancer in the UK in 2011), and it is the nineteenth most common cause of cancer death (around 2,100 people died from the disease in 2012).
The highest incidence of oral and pharyngeal cancer was recorded in Denmark, with age-standardised rates per 100,000 of 13.0, followed by Lithuania (9.9) and the United Kingdom (9.8). Lithuania reported the highest incidence in men while Denmark reported the highest in women. The highest rates for mortality in 2012 were reported in Lithuania (7.5), Estonia (6.0) and Latvia (5.4). 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.
Hungary (23.3), Slovakia (16.4) and Romania (15.5) reported the highest incidences of oral and pharyngeal cancer. Hungary also recorded the highest incidence in both genders as well as the highest mortality rates in Europe. It is ranked third globally for cancer mortality rates. Cigarette smoking, excessive alcohol consumption, inequalities in the care received by cancer patients and gender-specific systemic risk factors have been determined as the leading causes for the high morbidity and mortality rates in Hungary.
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), France (23.1). France, Belgium and Netherlands ranks highest for females, with ASRs 7.6, 7.0, 7.0, respectively.
Incidence of oral and oropharyngeal cancers were recorded, finding Portugal, Croatia and Serbia to have highest rates (ASR per 100,000). These values are 15.4, 12 and 11.7, respectively.
In 2011, close to 37,000 Americans are projected to be diagnosed with oral or pharyngeal 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%.
Oral cancers overall risk higher in black males opposed to white males, however specific oral cancers-such as of the lip, have a higher risk in white males opposed to black males. Overall, rates of oral cancer between gender groups (male and female) seem to be decreasing, according to data from 3 studies 
Of all the cancers, oral cancer attributes to 3% in males, opposed to 2% in women. New cases of oral cancer in US as of 2013, approximated almost 66,000 with almost 14000 attributed from tongue cancer, and nearly 12000 from the mouth, and the remainder from the oral cavity and pharynx. In the previous year, 1.6% of lip and oral cavity cancers were diagnosed, where the age-standardised incidence rate (ASIR) across all geographic regions of United States of America estimates at 5.2 per 100,000 population. It is the 11th most common cancer in USA among males while in Canada and Mexico it is the 12th and 13th most common cancer respectively. The ASIR for lip and oral cavity cancer among men in Canada and Mexico is 4.2 and 3.1 respectively.
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-standardised 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 
Rates are increasing across both males and females. As of 2017, almost 50000 new cases of oropharyngeal cancers will be diagnosed, with incidence rates being more than twice as high in men than women.
Oral cancer is one of the most common types of cancer in Asia due to its association with smoking (tobacco, bidi), betel quid and alcohol consumption. Regionally incidence varies with highest rates in South Asia, particularly India, Bangladesh, Sri Lanka, Pakistan and Afghanistan. In South East Asia and Arab countries, although the prevalence is not as high, estimated incidences of oral cancer ranged from 1.6 to 8.6/ 100,000 and 1.8 to 2.13/ 100,000 respectively.  According to GLOBOCAN 2012, the estimated age-standardised rates of cancer incidence and mortality was higher in males than females. However, in some area, specifically South East Asia, similar rates were recorded for both genders. The average age of those diagnosed with oral sarcoma cell carcinoma is approximately 51-55. In 2012, there were 97,400 deaths recorded due to oral cancer 
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.
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 incidence rate of oral cancer is 2.6 for both sexes. The rate is higher in males at 3.3 and lower in females at 2.0.
The mortality rate is lower than the incidence rate at 1.6 for both sexes. The rate is again higher for males at 2.1 and lower for females at 1.3.
The following rates describe the number of new cases or deaths per 100 000 individuals per year. The incidence rate of oral cancer is 6.3 for both sexes; this is higher in males at 6.8-8.8 and lower in females at 3.7-3.9. 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.
|Location||Incidence per 100 000 individuals per year||Mortality per 100 000 individuals per year|
|Both sexes||Males||Females||Both sexes||Males||Females|
|Floor of mouth||0.9||1.4||0.5||0.2||0.3||0.1|
|Major salivary glands||1.2||1.6||0.9||0.3||0.4||0.2|
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