Oral cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Oral cancer (or mouth cancer) is a type of head and neck cancer that involves any cancerous tissue growth located in the oral cavity. Oral cancer is a malignant growth that affects any part of the oral cavity, including the lips, gums, tongue, inside lining of the cheeks, roof of the mouth and floor of the mouth. It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types.

Oral cancer can be classified into three types based on the potential to spread to other parts of the body such as malignant tumors,precancerous conditions, and benign tumors. Most common type of malignant tumor of the mouth is squamous cell carcinoma. Squamous cell carcinoma is further classified by macroscopic and microscopic features. About 5% of oral cavity cancers are rare, malignant tumors that start in different types of cells in the oral cavity. These include: salivarygland cancer, melanoma, bone and soft tissue sarcomas, lymphomas and extramedullary plasmacytomas, hodgkin lymphoma, and non-Hodgkin lymphoma metastatic cancer.    

It is understood that oral cancer occurs as a the result of carcinogen-metabolizing enzymes, alcohol, tobacco and genetic factors. Cytotoxic enzymes, such as alcohol dehydrogenase, result in the production of free radicals and DNA hydroxylated bases. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is cytotoxic in nature. Cigarette smoke has various carcinogens that can lead to oral cancers. Low-reactive, free radicals in cigarette smoke interact with redox-active metals in saliva. The development of oral cancer is the result of multiple genetic mutations. These mutations occur in tumor suppressor genes (TSGs) and oncogenes. Squamous cell carcinoma is the most common malignancy of the oral cavity. It typically has three gross morphological growth patterns: exophytic, ulcerative, and infiltrative. Microscopically, oral cancers are broadly based and invasive through papillary fronds. Oral cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses.The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen

Common causes of oral cancers include pre-malignant lesion, tobacco, alcohol, human papillomavirus, and hematopoietic stem cell transplantation. Seventy-five percent of oral cancer cases occur due to tobacco. It causes irritation of the mucous membrane in the mouth. HPV type 16 is the most common sub-type of human papilloma virus associated with oral cancer. 

Oral cancer must be differentiated from actinic keratosis, dermatologic manifestations of oral leukoplakia, erythroplasia, lichen planus, and mucosal candidiasis.

The prevalence of oral cancer is estimated to be 91, 200 cases annually. The incidence of oral cancer is approximately 10.5 adults per 100,000 individuals worldwide, with a mortality rate of 1.2 per 100,000 individuals each year. Males are more commonly affected by squamous cell cancer of the oral cavity than females. The male to female ratio is approximately 6 to 1. Females are more commonly affected with adenocarcinoma of the hard palate. Oral cavity cancer more commonly affects individuals of the black population. Oral cavity cancer typically affects individuals of the lower-income patients.

The most potent risk factor in the development of oral cancer is alcohol intake and tobacco use. The other risk factors include male gender, age over 55 years, ultraviolet light, Fanconi anemia, dyskeratosis congenita, HPV infection, graft-versus-host disease (GVHD), mouthwash and irritation from dentures.

There is insufficient evidence to recommend routine screening for oral cancer.

If left untreated, patients with oral cancer may progress to develop non-healing ulcer, which demonstrates growth over time. A neck mass may develop, possibly causing a mass defect. Depending on the extent of the tumor at the time of diagnosis, the prognosis varies. The 5-year survival rate for oral cancer diagnosed early is 75% compared to 20% for oral cancer diagnosed late. Complications of oral cancer include difficulty speaking, dysphagia , weight loss, bleeding and even death. 

According to the TNM staging system by the American Joint Committee on cancer, there are four stages of oral cancer based on the tumor size, lymph nodes involved, and metastasis.

A positive history of tobacco chewing or smoking, excessive alcohol intake, poor oral hygiene, metallic denture, betel quid use, diet rich in meats and HPV infection in sexual partner is suggestive of oral cancer. The most common symptoms of oral cancer include a sore, irritated lump or thick patch in the mouth, lip, or throat; a white or red patch in the mouth; persistent mouth pain; a lump in the neck; loose tooth; bleeding in the mouth; pain in one ear without hearing loss; weight loss, etc. 

Common physical examination findings of oral cancer include a lump or thickening in the oral soft tissues, soreness, difficulty chewing or swallowing, ear pain, difficulty moving the jaw or tongue, hoarseness, numbness of the tongue or swelling of the jaw that causes dentures to fit poorly.

Some patients with oral cancer may have elevated liver function tests, abnormal urea and electrolyte measurements, elevated calcium levels. Serum ferritin, alpha-anti-trypsin, and alpha-anti-glycoprotein levels may be increased in high-stage cancer of oral cavity; while those at any stage of the disease will have increased haptoglobin levels. Prealbumin levels are decreased slightly in persons at any stage.

There are no x-ray findings associated with oral cancer. However, a chest x-ray may be helpful to diagnose metastases in the lungs, a site for second primary carcinoma and metastasis in hilar lymph nodes, ribs, or vertebrae. Jaw radiography may show invasion but may be inadequate to exclude bone invasion.

Neck CT scans may be helpful in the diagnosis of oral cancer. CT scans can provide information about the size, shape and position of any tumor and may help identify enlarged lymph nodes. 

Neck MRI’s may be helpful in the diagnosis of oral cancer. MRI’s can provide detailed view of cancer spread. Magnetic resonance imaging offers an advantage over computed tomographic scans in the detection and localization of head and neck tumors and in the distinction of lymph nodes from blood vessels.

A PET scan may be diagnostic of spread of oral cancer. FDG-PET (18-fluorodeoxyglucose positron emission tomography) scanning is useful to identify the extent of cervical node metastasis.

Biopsy of the tumor tissue is diagnostic of oral cancer. Other diagnostic studies for oral cancer include endoscopy, indirect pharyngoscopy, laryngoscopy, exfoliative cytology, barium swallow, chest x-ray and bone scan.

The predominant therapy for oral cancer is surgical resection, radiation therapy, or a combination of both. Adjunctive chemotherapy, radiation, chemotherapy may be required. Radiation in the form of external-beam radiation therapy (EBRT) or interstitial implantation is used. Advantages of radiotherapy are that normal anatomy or function are maintained, and general anesthesia is not needed. Disadvantages of radiotherapy are that it is inefficient to treat large tumors, subsequent surgery is more difficult, oral mucositis, dry mouth (xerostomia), osteoradionecrosis (ORN) etc.

Surgery is the mainstay of treatment for oral cancer. Surgical resection of full-extent of the oral cavity lesion should be done. Only surgical resection is done when oral cancer has been detected early but not yet metastasized. In advanced-stages and recurrent cancers, surgery is done in combination with radiation therapy, chemotherapy or targeted therapy. Depending on the stage of oral cancer, one or more of the various procedures listed are recommended: Tumor resection, mohs micrographic surgery, full or partial mandible resection, glossectomy, maxillectomy, Laryngectomy, Neck dissection, partial or selective neck dissection, modified radical neck dissection or radical neck dissection.

Effective measures for the primary prevention of oral cancer include tobacco cessation, alcohol cessation, HPV vaccine, and avoiding excessive sun exposure.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Hippocrates described the term “aphthae” in relation to the disorders of mouth in 370-460 B.C. By 1928, V. P. Blair of St. Louis was the first to advocate surgery as the best management for oral cancers. Cytotoxic chemotherapy was a major initiative in the 1970’s for the patients unfit for surgeries.

• Between 370-460 B.C., in relation to disorders of the mouth the term “aphthae” was first used by Hippocrates.^[1]
• In 1838, the term melanoma was first proposed by Sir Robert Carswell, a British pathologist.^[2]
• In 1875, Bernard von Langenbeck respected the ramus of the mandible in continuity with the primary tumor.^[3]
• By 1928, V. P. Blair of St. Louis was the first to advocate surgery as the best management for oral cancers.
• A major initiative of the 1970’s and 1980’s was cytotoxic chemotherapy for patients unfit for surgeries.
• Verrucous carcinoma was first discovered in 1948 by Lauren V. Ackerman, an American physician.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2], Simrat Sarai, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Oral cancer can be classified into three types based on the potential to spread to other parts of the body such as malignant tumors,precancerous conditions, and benign tumors. Most common type of malignant tumor of the mouth is squamous cell carcinoma. Squamous cell carcinoma is further classified based on macroscopic and microscopic features. About 5% of oral cavity cancers are rare malignant tumors that start in different types of cells in the oral cavity. These include salivary gland cancer, melanoma, bone and soft tissue sarcomas, Lymphomas and extramedullary plasmacytomas, Hodgkin lymphoma, and non-Hodgkin lymphoma metastatic cancer.

• Malignant tumors of the oral cavity are cancerous growths that have the potential to spread (metastasize) to other parts of the body.
• The oral cavity is lined with squamous epithelium, which is formed by flat, scale-like cells called squamous cells.
• The most common oral cavity cancer starts in these cells and is called squamous cell carcinoma (SCC).

• Squamous cell carcinomas (SCC) make up 95% of all oral cavity cancers. They are classified based on macroscopic or microscopic features.
  • Macroscopic features:
  • Can be seen without a microscope
  • Squamous cell carcinomas are described as following based on macroscopic features:

• Infiltrative – Cancer is growing into deep layers of the oral cavity
• Exophytic – Cancer is growing outwards from the surface of the oral cavity
• Verrucous– Cancer has a wart-like appearance
• Ulcerated– Cancer appears as an open sore
• Flat – Cancer appears as an abnormal area in the lining of the oral cavity

• Microscopic features:
• Squamous cell carcinomas (SCC) are further divided into the following types based on microscopic features:

• Classical or conventional SCC: Most cancers of the oral cavity are classical or conventional squamous cell carcinoma. This type of SCC starts in the squamous epithelium that lines the oral cavity and occurs most often on the lower lip, tongue and floor of the mouth.
• Variants of SCC: These squamous cell carcinomas have distinct microscopic features that make them look and behave differently from classical SCC.

• Verrucous carcinoma
• Basaloid SCC
• Papillary SCC
• Spindle cell carcinoma (SpCC)
• Acantholytic SCC
• Adenosquamous carcinoma
• Lymphoepithelial carcinoma

• About 5% of oral cavity cancers are rare, malignant tumors that start in different types of cells in the oral cavity.
  • Salivary gland cancer
  • Melanoma
  • Bone and soft tissue sarcomas
  • Lymphomas and extramedullary plasmacytomas
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Metastatic cancer

• Several types of non-cancerous tumors and tumor-like conditions can arise in the oral cavity and oropharynx.
• A pre-malignant (or precancerous) lesion is defined as a benign, morphologically-altered tissue that has a greater than normal risk of becoming malignant.
• There are several different types of pre-malignant lesions 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”).
• The most common pre-cancerous conditions of the oral cavity are:
  • Leukoplakia
  • Erythroplakia
  • Erythroleukoplakia
  • Proliferative verrucous leukoplakia (PVL)
  • Oral submucous fibrosis

• Benign tumors: There are many different types of benign oral cavity tumors.
  • Hyperplasia
  • Papillomas
  • Pleomorphic adenoma
  • Soft tissue tumors
    • Lymphangioma
    • Hemangioma
    • Neurofibroma
    • Lipoma
• Benign odontogenic tumors and cysts
  • Osteoma
  • Ossifying fibroma
• Benign conditions
  • Candidiasis (thrush)
  • Aphthous ulcers (canker sores)
  • Recurrent herpes labialis (cold sores)
  • Erythema migrans (geographic tongue)
  • Hairy tongue
  • Lichen planus
  • Frictional hyperkeratosis
  • Mucocele

The TNM classification of oral cavity carcinoma is as follows:^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2], Simrat Sarai, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

It is understood that oral cancers occur as a the result of carcinogen–metabolizing enzymes, alcohol, tobacco and genetic factors. Cytotoxic enzymes such as alcohol dehydrogenase result in the production of free radicals and hydroxylation of DNA base units. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature. Cigarette smoke has various carcinogens, which can lead to oral cancers. Low-reactive free radicals in cigarette smoke interact with redox-active metals in saliva.The development of oral cancer is the result of multiple genetic mutations. These mutations occur in tumor suppressor genes (TSGs) and oncogenes. Squamous cell carcinoma is the most common malignancy of the oral cavity. It typically has three gross morphological growth patterns, which are exophytic, ulcerative, and infiltrative. Microscopically, oral cancers are broadly based and invasive through papillary fronds. Oral cancer consists of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses.The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen.

It is understood that oral cancer occurs as a the result of carcinogen–metabolizing enzymes, alcohol, tobacco and genetic factors.

• Carcinogen–metabolizing enzymes are known to cause cancer in some patients.
• Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
  • Free radicals
  • DNA hydroxylated bases
• These cytotoxic enzymes dominantly play a key role in the development of oral squamous cell carcinoma.

• Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is cytotoxic in nature.
• Cytochrome P450 IIEI (CYP2E1) also metabolizes ethanol to acetaldehyde.
• Alcohol dehydrogenase type 3 genotype predisposes to oral squamous cell carcinoma.
• Carcinogenic potential increases when combined with tobacco use.

• Cigarette smoke has various carcinogens, which can lead to oral cancers.
• Low reactive free radicals in cigarette smoke interact with redox-active metals in saliva.
• saliva then looses its antioxidant potential and becomes a potent pro-oxidant milieu.^[1]

• Most cancers of the oral cavity are classical or conventional squamous cell carcinoma.
• This type of SCC starts in the squamous epithelium, which lines the oral cavity and occurs most often on the lower lip, tongue and floor of the mouth.
• The microscopic features of classical SCC involve
  • Keratin pearls
    • These are circular layers of squamous cells that surround keratin (a tough fibrous protein).

• Cancer starts in the squamous cells of the epithelium, and then invades the deeper layers of the oral cavity.

• The following squamous cell carcinomas have distinct microscopic features that make them look and behave differently from classical SCC:

• Verrucous carcinoma
  • These tumors make up less than 5% of all oral cavity tumors.
  • They have a wart-like appearance and develop most often on the gums (gingiva), lining of the cheeks (buccal mucosa) and larynx.
  • Verrucous carcinomas are low grade, slow-growing and rarely spread.
  • They are associated with the chronic use of snuff or chewing tobacco.
• Basaloid SCC
  • This is a rare but aggressive sub-type of squamous cell carcinoma.
  • It is more common in men older than 60 years old.
• Papillary SCC
  • This is a rare sub-type of squamous cell carcinoma that grows outward from the surface of the epithelium (exophytic).
  • HPV infections may have a role in the development of this type of cancer.
• Spindle cell carcinoma (SpCC)
  • This is an aggressive, rare variant of squamous cell carcinoma.
  • These tumors contain a mixture of conventional squamous cell carcinoma and spindle cells that resemble a sarcoma.
  • It is also known as sarcomatoid carcinoma, pseudosarcoma, carcinosarcoma, pleomorphic carcinoma, metaplastic carcinoma, collision tumor and Lane tumor.

• Acantholytic SCC
  • This is a rare variant of SCC in which the connections between the malignant squamous cells are broken down.
  • This results in microscopic spaces in the tumor tissue, which appear like glands or vascular spaces.
• Adenosquamous carcinoma
  • This is a very rare, aggressive type of squamous cell carcinoma.
  • It looks like classical squamous cell carcinoma but also has mucus-producing gland cells.
• Lymphoepithelial carcinoma
  • This is a rare sub-type of squamous cell carcinoma.
  • The microscopic appearance is similar to undifferentiated nasopharyngeal carcinoma.
  • It is also known as undifferentiated carcinoma.

• The development of oral cancer is the result of multiple genetic mutations.
• These mutations include:
  • Tumor suppressor genes (TSGs)
  • Oncogenes

• Oral cavity cancer may be the result of an allelic imbalance, which is caused by chromosomal changes- particularly in chromosome 3, 9, 11 and 17.
• These changes lead to mutation in tumor suppressor genes (TSGs).
• In non-cancerous situations, TSGs modulate normal growth.
• Mutation of these TSGs lead to dysfunctional growth control.
• Mutation most commonly occurs in one of the following:
  • Short arm of chromosome 3
  • TSG termed P16 on chromosome 9
  • TSG termed TP53 on chromosome 17
• The Cytochrome P450 genotype is related to mutations in some TSGs and leads to oral squamous cell carcinoma.
• In western countries (eg. United Kingdom, United States, or Australia), TP53 mutations are the most common molecular change that leads to oral squamous cell carcinoma.

• Cancer may also occur if there is mutation in other genes that control cell growth, typically oncogenes.
• Oncogenes most commonly involved are:
  • Chromosome 11 (PRAD1)
  • Chromosome 17 (Harvey ras [H-ras])
• In eastern countries (eg. India or Southeast Asia), ras oncogenes is a more common cause of oral squamous cell carcinoma.

• Squamous cell carcinoma is the most common malignancy of the oral cavity.
• It typically has three gross morphological growth patterns, which are exophytic, ulcerative, and infiltrative.
• The infiltrative and ulcerative are the growth patterns most commonly observed in the oral cavity.
• The macroscopic appearance of oral cancer depends on the following:
  • Duration of the lesion
  • The amount of keratinization
  • The changes in the adjoining mucosa
  • A fully developed oral cavity lesion appears as an exophytic bulky lesion that is gray to grayish-red and has a rough, shaggy, or papillomatous surface

• Microscopically, oral cancers are broadly based and invasive through papillary fronds.
• Oral cancer constitutes of highly-differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses.
• The surface of the lesion is covered with compressed invaginating folds of keratin layers.
• A stroma-like inflammatory reaction and a blunt pushing margin may be seen.

• SCC is subdivided by the WHO into:^[2]
  • Keratinizing type: Worst prognosis
  • Undifferentiated type: Intermediate prognosis and EBV association^[3]
  • Non-keratinizing type: Good prognosis and EBV association

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2], Simrat Sarai, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Common causes of oral cancers include premalignant lesions, tobacco, alcohol, human papillomavirus, and hematopoietic stem cell transplantation. Tobacco use is the cause of 75% oral cancer cases . It causes an irritation of mucous membrane in the mouth. HPV type 16 is the most common sub-type of human papilloma virus associated with oral cancer.

Common causes of oral cancer include:

• Pre-malignant lesion^[1]
  • Benign and morphologically-altered tissue
  • Pre-malignant lesions are of various types:
    • Leukoplakia – benign white patches
    • Erythroplakia – red patches
    • Erythroleukoplakia – mixed red and white patches
    • Lichen planus
    • Oral sub-mucous fibrosis – very common in Indian sub-continents
    • actinic cheilitis

• Tobacco
  • 75% cases of oral cancers occur due to tobacco use.
  • Use of it causes irritation of the mucous membrane in the mouth.
  • Both smoking and chewing tobacco can lead to irritation of mucous membrane of the mouth.
  • 60 types of carcinogens are known to be present in tobacco smoke.
  • If any form of tobacco use is combined with heavy alcohol intake, the carcinogenic potential increases.

• Alcohol^[2]
  • Heavy alcohol intake can lead to cancer of pharynx and larynx.
  • Carcinogenic potential increases when combined with tobacco use.

• Human Papilloma Virus( HPV)
  • HPV type 16 is the most common sub-type associated with oral cancer.
  • Unprotected oral sexual behaviors with a patient suffering from HPV can transmit this virus.^[3]
  • It most commonly involves the tonsils, which are at the base of the tongue and the oropharynx.

• Hematopoietic stem cell transplantation
  • This causes an increased risk for squamous cell carcinoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

There are different types of cancers of the oral cavity and oropharynx. It is important that they are differentiated from one another.

The table below outlines the different types of tumors/cancers present in the oral cavity and oropharynx and how they can be differentiated from one another.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2], Simrat Sarai, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

The prevalence of oral cancer is estimated to be 91,200 cases annually. The incidence of oral cancer is approximately 10.5 adults per 100,000 individuals worldwide with a mortality rate of 1.2 per 100,000 individuals each year. Males are more commonly affected by squamous cell cancer of the oral cavity than females. The male to female ratio is approximately 6 to 1. Females are more commonly affected with adenocarcinoma of the hard palate. Oral cavity cancer usually affects individuals of the black population. Oral cavity cancer usually affects individuals of the lower-income patients.

• Oral cancer is the 11th most common malignancy, worldwide.^[1]
• In the United States, it is estimated that approximately 91,200 persons are living with oral cancer.
• It is estimated that about 14% cancers of head and neck are oral cancers (excluding lip cancer).

• The incidence of oral cancer is approximately 8.4 adults per 100,000 individuals worldwide with a mortality rate of 1.2 per 100,000 individuals each year.^[2]
• From 2010 to 2014, the estimated age-adjusted incidence of cancer of the oral cavity and pharynx in the United States was 11.2 cases per 100,000 persons per year.^[3] 
• It is estimated that there will be 49,670 new cases of oral cavity and pharynx cancer diagnosed in the United States in 2017 and 9,700 deaths due to this disease.^[4]

• Males are more commonly affected by squamous cell cancer of the oral cavity than females.^[5]
• The male to female ratio is approximately 6:1.^[5]

• Females are more commonly affected with adenocarcinoma of the hard palate.

• The incidence of oral cavity cancer increases with age; the median age at diagnosis is 65 years.

• Oral cavity cancer usually affects individuals of the black population.
• Oral cavity cancer usually affects individuals of the lower-income patients.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2], Simrat Sarai, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

The most potent risk factor in the development of oral cancer is alcohol intake and tobacco use. The other risk factors include male gender, age over 55 years, ultraviolet light, Fanconi anemia, dyskeratosis congenita, HPV infection, graft-versus-host disease (GVHD), mouthwash and irritation from dentures.

• The most potent risk factor in the development of oral cavity cancer is tobacco and alcohol use.
• Other risk factors include:
  • Lifestyle
    • Betel quid use^[1]
  • Genetics
    • Fanconi anemia
    • Dyskeratosis congenita
    • Family history of squamous cell carcinoma
• Infectious agents:
  • Human papillomavirus (HPV)^[2][3]
  • Candida albicans^[4] 
• General
  • Male gender^[5]
  • Ultraviolet light^[6]
  • Age over 55 years^[7]
  • Graft-versus-host disease (GVHD)^[8]
  • Immune system suppression
  • Lichen planus

• Less common risk factors for the development of oral cancer include:
  • According to a study: poor dental hygiene or health and use of dentures made out of metal can lead to increased risk of oral cancer.^[9] 
  • Diet
    • Diet low in fruits and vegetables and high in consumption of meats is associated with oral cavity cancer.   
  • Mouthwash^[10]
  • Low socioeconomic status

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

There is insufficient evidence to recommend routine screening for oral cancer.

• There is insufficient evidence to recommend routine screening for oral cancer.^[1]
• There is no country that has any routine screening program for oral cancer.
• There is insufficient evidence to support any screening modality that might decrease mortality in oral cancer.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

If left untreated, patients with oral cancer may progress to develop a non-healing ulcer, which demonstrates growth over time. A neck mass may develop, which may cause a mass defect. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. The 5-year survival rate for oral cancer that is diagnosed early is 75%, compared to 20% for late diagnosis. Complications of oral cancer include difficulty speaking, dysphagia, weight loss, bleeding and even death.

• Oral cancers usually present late, as they are usually painless and often ignored by the patient.
• Eventually they present as a non-healing ulcer, which demonstrates growth over time.
• Due to the extensive lymphatic drainage of the oral cavity, nodal metastases are common at the time of diagnosis.
• A neck mass may be the presenting complaint.
• Because of the difficulties with direct visualization, they may extend into the tongue or have clinical lymph node metastases before the diagnosis is established.
• As the tumors enlarge, they may cause a mass effect, which can lead to respiratory compromise when the patient presents late in their illness.[1]

• The prognosis depends on the following:
  • Stage of the cancer
  • Number and size of lymph nodes with cancer
  • HPV infection of the oropharynx
  • Smoking history more than a ten pack-year

• 5-year survival rate for oral cancer:
  • Diagnosed early – 75%
  • Diagnosed late – 20%
  • Localized disease at diagnosis – 83%
  • Cancer spread to other parts of the body – 32%
• Cure rate:
  • 90% – If cancer is found early and before it has spread to other tissues
• More than 50% oral cancers are diagnosed when they have spread to throat and neck.

• Direct surgical complications include infection, bleeding, aspiration, wound breakdown, flap loss, and fistula.

• Complications of chemotherapy includes the following:^[1]
  • Neurotoxicity– This complication is a side-effect of certain classes of drugs, such as the vinca alkaloids.
  • Bleeding
• Complications of radiation therapy includes the following:^[2]
  • Radiation caries
  • Trismus
  • Osteonecrosis
• Complications common to both chemotherapy and radiation include the following:^[3]
  • Oral mucositis
  • Chronic dysphagia
  • Anemia
  • Pharyngocutaneous fistula
  • Aspiration
  • Infections such as viral, bacterial, and fungal that results from myelosuppression, xerostomia, and damage to the mucosa from radiotherapy or chemotherapy
  • Xerostomia
  • Functional disabilities such as impaired ability to swallow, eat, taste and speak because of trismus, dry mouth, mucositis, and infection
  • Nutritional compromise, such as poor nutrition from eating difficulties caused by dry mouth, mucositis, dysphagia, and loss of taste.
  • Abnormal dental development
    • Altered tooth development, craniofacial growth, or skeletal development in children- secondary to high doses of chemotherapy and radiotherapy before age 9

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