Cancer of the Mouth and Throat (Oral Cancer)

Picture of oral cancer (mouth cancer)

The oral cavity (mouth) and the upper part of the throat (pharynx) have roles in many important functions, including breathing, talking, chewing, and swallowing. The mouth and upper throat are sometimes referred to as the oropharynx or oral cavity. The important structures of the mouth and upper throat include lips, inside lining of the cheeks (mucosa), teeth, gums (gingiva), tongue, floor of the mouth, back of the throat, including the tonsils (oropharynx), roof of the mouth (the bony front part [hard palate] and the softer rear part [soft palate]), the area behind the wisdom teeth, and the salivary glands.

Many different cell types make up these different structures. Cancer occurs when normal cells undergo a transformation whereby they grow and multiply without normal controls. Malignant tumors (cancers) of the oral cavity can encroach on and invade neighboring tissues. They can also spread to remote sites in the body through the bloodstream or to lymph nodes via the lymph vessels. The process of invading and spreading to other organs is called metastasis.

Tumors in the mouth (oral cancer) and throat (oropharyngeal cancer) include both benign (not cancer) and malignant types. Benign tumors, although they may grow and penetrate below the surface layer of tissue, do not spread by metastasis to other parts of the body. Benign tumors of the oropharynx are not discussed in this article.

Each year, almost 50,000 people in the U.S. will get oral cavity or oropharyngeal cancer. Around 9,700 people will die of these cancers.

Premalignant conditions are cell changes that are not cancer but which may become cancer if not treated.

• Dysplasia is another name for these precancerous cell changes It means abnormal growth.
• Dysplasia can be detected only by taking a biopsy of the lesion.
• Examining the dysplastic cells under a microscope indicates how severe the changes are and how likely the lesion is to become cancerous.
• The dysplastic changes are usually described as mild, moderately severe, or severe.

The two most common kinds of premalignant lesions in the oropharynx are leukoplakia and erythroplakia.

• Leukoplakia is a white or whitish area on the tongue or inside of the mouth. It can often be easily scraped off without bleeding and develops in response to chronic (long-term) irritation. Only about 5% of leukoplakias are cancerous at diagnosis or will become cancerous within 10 years if not treated.
• Erythroplakia is a raised, red area. If scraped, it may bleed. Erythroplakia is generally more severe than leukoplakia and has a higher chance of becoming cancerous over time.
• Mixed white and red areas (erythroleukoplakia) can also occur and represent premalignant lesions of the oral cavity.
• These are often detected by a dentist at a routine dental examination.

Several types of malignant cancers occur in the mouth and throat.

• Squamous cell carcinoma is by far the most common type, accounting for more than 90% of all cancers. These cancers start in the squamous cells, which form the surface of much of the lining of the mouth and pharynx. They can invade deeper layers below the squamous layer.
• Other less common cancers of the mouth and throat include tumors of the minor salivary glands called adenocarcinomas and lymphoma.
• Cancers of the mouth and throat do not always metastasize, but those that do usually spread first to the lymph nodes of the neck. From there, they may spread to more distant parts of the body.
• Cancers of the mouth and throat occur in twice as many men as women.
• These cancers can develop at any age but occur most frequently in people aged 45 years and older.
• Incidence rates of mouth and throat cancers vary widely from country to country. These variations are due to differences in risk factor exposures.

People may not notice the very early symptoms or signs of oral cancer. People with an oropharyngeal cancer may notice any of the following signs and symptoms:

• A painless lump on the lip, in the mouth, or in the throat
• A sore or ulceration on the lip or inside the mouth that does not heal
• Painless white patches or red patches on the gums, tongue, or lining of the mouth
• Unexplained pain, bleeding, or numbness inside the mouth
• A sore throat that does not go away
• Pain or difficulty with chewing or swallowing
• Swelling of the jaw
• Hoarseness or other change in the voice
• Pain in the ear

Oral squamous cell cancer appearing as a tongue ulcer. SOURCE: Image reprinted with permission from Medscape.com, 2012.

These symptoms are not necessarily signs of cancer. Mouth sores and other symptoms may be caused by many other less serious conditions.

Today the understanding of oral health and the cause of cancers (especially those of the oropharynx) has changed dramatically. Historically most cancer of the head and neck was attributed to tobacco and alcohol use. Today we know that this explanation is both incomplete and often inaccurate.

Anywhere from 50%-90% of oropharynx squamous cell carcinomas are known to be caused by HPV (human papillomavirus) infection. Testing the cancers shows evidence of HPV infection. Such cancers are said to be HPV positive or HPV+.

The human papillomavirus can cause a sexually transmissible viral infection. Eighty percent of people between 18 and 44 have had oral sex with an opposite sex partner, likely accounting for much of the oral HPV infections observed. There are many forms of HPV. The high risk subtypes of HPV are responsible for 90% of cancer of the cervix. They also play an important role in other genital area cancers. These same subtypes of HPV, especially types 16 and 18, are found present in oropharyngeal area cancers.

HPV+ cancers occur in people who may or may not have a history of excessive tobacco or alcohol use. HPV negative, HPV-, cancers of the oropharynx are virtually always found in those with the history of heavy alcohol and tobacco use.

Both smoking and "smokeless" tobacco (snuff and chewing tobacco) increase the risk of developing cancer in the mouth or throat.

• All forms of smoking are linked to these cancers, including cigarettes, cigars, and pipes. Tobacco smoke can cause cancer anywhere in the mouth and throat as well as in the lungs, the bladder, and many other organs in the body. Pipe smoking is particularly linked with lesions of the lips, where the pipe comes in direct contact with the tissue.
• Smokeless or chewing tobacco is linked with cancers of the cheeks, gums, and inner surface of the lips. Cancers caused by smokeless tobacco use often begin as leukoplakia or erythroplakia.

Other risk factors for mouth and throat cancer include the following:

• Alcohol use: At least three quarters of people who have an HPV negative mouth and throat cancer consume alcohol frequently. People who drink alcohol frequently are six times more likely to develop one of these cancers. People who both drink alcohol and smoke often have a much higher risk than people who use only tobacco alone.
• Sun exposure: Just as it increases the risk of skin cancers, ultraviolet radiation from the sun can increase the risk of developing cancer of the lip. People who spend a lot of time in sunlight, such as those who work outdoors, are more likely to have cancer of the lip.
• Chewing betel nut: This prevalent practice in India and other parts of South Asia has been found to result in mucosa carcinoma of the cheeks. Mucosa carcinoma accounts for less than 10% of oral cavity cancers in the United States but is the most common oral cavity cancer in India.

These are risk factors that can be avoided in some cases. For example, one can choose to not smoke, thus lowering the risk of mouth and throat cancer. The following risk factors are outside of a person's control:

• Age: The incidence of mouth and throat cancers increases with advancing age.
• Sex: Mouth and throat cancer is twice as common in men as in women. This may be related to the fact that more men than women use tobacco and alcohol.

The relationship between these risk factors and an individual's risk is not well understood. Many people who have no risk factors develop mouth and throat cancer. Conversely, many people with several risk factors do not. In large groups of people, these factors are linked with higher incidence of oropharyngeal cancers.

If a person has any of the symptoms of head and neck cancer, he or she should make an appointment to see a primary care professional or dentist right away.

• Cancers of the mouth and throat are often found on routine dental examination. If a dentist should find an abnormality, he or she will probably refer the person to a specialist in ear, nose, and throat medicine (an otolaryngologist) or recommend that they see a primary health care professional right away.
• If symptoms are found that suggest a possible cancer, or if an abnormality is found in the oral cavity or pharynx, the health care professional will immediately begin the process of identifying the type of abnormality. The goal will be to rule out or confirm the diagnosis of cancer. He or she will interview the patient extensively, asking questions about medical and surgical history, medications, family and work history, and habits and lifestyle, focusing on the risk factors for oropharyngeal cancers.
• At some point during this process, the person will probably be referred to a physician who specializes in treating cancers of the mouth and throat. Many cancer specialists (oncologists) specialize in treating cancers of the head and neck, which includes cancers of the oropharynx. Every person has the right to seek treatment where he or she wishes. The patient may want to consult with two or more specialists to find one who makes him or her feel most comfortable.
• The patient will undergo a thorough examination and cancer screening of the head and neck to look for lesions and abnormalities. A mirror exam and/or an indirect laryngoscopy (see below for explanation) will most likely be done to view areas that are not directly visible on examination, such as the back of the nose (nasopharyngoscopy), the throat (pharyngoscopy), and the voice box (laryngoscopy).
• The indirect laryngoscopy is performed with the use of a thin, flexible tube containing fiberoptics connected to a camera. The tube is moved through the nose and throat and the camera sends images to a video screen. This allows the physician to see any hidden lesions.
• In some cases, a panendoscopy may be necessary. This includes endoscopic examination of the nose, throat, and voice box as well as the esophagus and airways of the lungs (bronchi). This is done in an operating room while the patient is under general anesthesia. This gives the most exhaustive possible examination and can permit biopsies of areas suspicious for malignancy.
• The complete physical examination will look for signs of metastatic cancer or other medical conditions that could affect the diagnosis or treatment plan.

No blood tests can identify or even suggest the presence of a cancer of the mouth or throat. The appropriate next step is biopsy of the lesion. This means to remove a sample of cells or tissue (or the entire visible lesion if small) for examination.

• There are several techniques for taking a biopsy in the mouth or throat. The sample can be simply scraped from the lesion, removed with a scalpel, or withdrawn with a needle.
• This can sometimes be done in the medical office; other times, it needs to be done in a hospital.
• The technique is dictated by the size and location of the lesion and by the experience of the person collecting the biopsy.
• If there is a mass in the neck, that may be sampled as well, usually by fine-needle aspiration biopsy.

After the sample(s) is removed, it will be examined by a doctor who specializes in diagnosing diseases by examining cells and tissues (pathologist).

• The pathologist looks at the tissue under a microscope after treating it with special stains to highlight certain abnormalities.
• If the pathologist finds cancer, he or she will identify the type of cancer and report back to the health care professional.

If your lesion is cancer, the next step is to stage the cancer. This means to determine the size of the tumor and its extent, that is, how far it has spread from where it started. Staging is important because it not only dictates the best treatment but also the prognosis for survival after treatment.

• In oropharyngeal cancers, the stage is based on the size of the tumor, involvement of the lymph nodes in the head and neck, and evidence of spread to distant parts of the body.
• Like many cancers, cancers of the oral cavity and pharynx are staged as 0, I, II, III, and IV, with 0 being the least severe (cancer has not yet invaded the deeper layers of tissue under the lesion) and IV being the most severe (cancer has spread to an adjacent tissue, such as the bones or skin of the neck, to many lymph nodes on the same side of the body as the cancer, to a lymph node on the opposite side of the body, to involve critical structures such as major blood vessels or nerves, or to a distant part of the body).

Stage is determined from the following information:

• Physical examination findings
• Endoscopic findings
• Imaging studies: A number of tests may be done, including X-rays (including a Panorex, a panoramic dental X-ray), CT scan, MRI, PET scan, and, occasionally, a nuclear medicine scan of the bones to detect metastatic disease

After evaluation by a surgical or radiation oncologist to treat the cancer, there will be ample opportunity to ask questions and discuss which treatments are available.

• The doctor will explain each type of treatment, elaborate the pros and cons, and make recommendations.
• Treatment for head and neck cancer depends on the type of cancer and whether it has affected other parts of the body. Factors such as age, overall health, and whether the patient has already been treated for the cancer before are included in the treatment decision-making process.
• The decision of which treatment to pursue is made with the doctor (with input from other members of the care team) and family members, but ultimately, the decision is the patient's.
• A patient should be certain to understand what will be done and why, and what he or she can expect from the choices. With oral cancers, it is especially important to understand the side effects of treatment.

Like many cancers, head and neck cancer is treated on the basis of cancer stage. The most widely used therapies are surgery, radiation therapy, and chemotherapy.

• The medical team may include an ear, nose, and throat surgeon; an oral surgeon; a plastic surgeon; and a specialist in prosthetics of the mouth and jaw (prosthodontist), as well as a specialist in radiation therapy (radiation oncologist) and medical oncology.
• Because cancer treatment can make the mouth sensitive and more likely to be infected, the doctor will probably advise the patient to have any needed dental work done before receiving treatments.
• The team will also include a dietitian to ensure that the patient gets adequate nutrition during and after therapy.
• A speech therapist may be needed to help the patient recover his or her speech or swallowing abilities after treatment.
• A physical therapist may be needed to help the patient recover function compromised by loss of muscle or nerve activity from the surgery.
• A social worker, counselor, or member of the clergy will be available to help the patient and his or her family cope with the emotional, social, and financial toll of your treatment.

Treatment falls into two categories: treatment to fight the cancer and treatment to relieve the symptoms of the disease and the side effects of the treatment (supportive care).

Surgery is the treatment of choice for early stage cancers and many later stage cancers. The tumor is removed, along with surrounding tissues, including but not limited to the lymph nodes, blood vessels, nerves, and muscles that are affected.

Radiation therapy involves the use of a high-energy beam to kill cancer cells.

• Radiation can be used instead of surgery for many stage I and II cancers, because surgery and radiation have equivalent survival rates in these tumors. In stage II cancers, tumor location determines the best treatment. The treatment that will have the fewest side effects is usually chosen.
• Stage III and IV cancers are most often treated with both surgery and radiation. The radiation is typically given after surgery. Radiation after surgery kills any remaining cancer cells.
• External radiation is given by precisely targeting a beam at the tumor. The beam goes through the healthy skin and overlying tissues to reach the tumor. These treatments are given at the cancer center. Treatments are usually given once a day, five days a week, for about six weeks. Each treatment takes only a few minutes. Giving radiation this way keeps the doses small and helps protect healthy tissues. Some cancer centers are experimenting with giving radiation twice a day to see if it increases survival rates.
• Unfortunately, radiation affects healthy cells as well as cancer cells. Damage to healthy cells accounts for the side effects of radiation therapy. These include sore throat, dry mouth, cracked and peeling lips, and a sunburn-like effect on the skin. It can cause problems with eating, swallowing, and speaking. The patient may also feel very tired during, and for some time after, these treatments. External beam radiation can also affect the thyroid gland in the neck, causing the level of thyroid hormone to be low. This can be treated.
• Internal radiation therapy (brachytherapy) can avoid these side effects in some cases. This involves implanting tiny radioactive "seeds" directly into the tumor or in the surrounding tissue. The seeds emit radiation that destroys tumor cells. This treatment takes several days and the patient will have to stay in the hospital during the treatment. It is less commonly used for oral cancers than external radiation therapy.

Chemotherapy refers to the use of drugs to attempt to kill cancer cells. Chemotherapy is used in some cases before surgery to reduce the size of the cancer, or after surgery, or in combination with radiation to enhance the local, regional, and distant control of the disease and hopefully the cure rate of the treatment. Hidden cancer cells may escape the area being treated by surgery or radiation and it is those cells which result in recurrences of the cancer and which chemotherapy hopes to prevent by killing such cells. A person's treatment plan will be individualized for his or her specific situation. Targeted therapy refers to the use of newer drugs or other substances that block the growth and spread of cancer by interfering with molecules specific to the particular type of tumor. Older chemotherapy drugs are less specific, or targeted, but rely on cancer cells being less able to recover from their effects than can normal cells.

Treatment of recurrent tumors, like that of primary tumors, varies by size and location of the recurrent tumor. The treatment given previously is also taken into account. For instance, sometimes further surgery can be done. If a site of recurrence was already treated by external radiation therapy may be difficult to treat a second time with external radiation. Often chemotherapy may be tried if a recurrence is inoperable, or further radiation with curative intent is not feasible.

Weight loss is a common effect in people with head and neck cancers. Discomfort from the tumor itself, as well as the effects of treatment on the chewing and swallowing structures and the digestive tract, often prevents eating.

Medications will be offered to treat some of the side effects of therapy, such as nausea, dry mouth, mouth sores, and heartburn.

The patient will probably see a speech therapist during and for some time after treatment. The speech therapist helps the patient learn to cope with the changes in the mouth and throat after treatment so that he or she can eat, swallow, and talk.

Oral surgery for cancer may be simple or very complicated. This depends on how far the cancer has spread from where it started. Cancers that have not spread can often be removed quite easily, with minimal scarring or change in appearance.

If the cancer has spread to other structures, those structures must also be removed. This may include small muscles in the neck, lymph nodes in the neck, salivary glands, and nerves and blood vessels that supply the face. Structures of the jaw, chin, and face, as well as teeth and gums, may also be affected.

If any of these structures are removed, the person's appearance will change. The surgery will also leave scars that may be visible. These changes can sometimes be extensive. A plastic surgeon may take part in the planning or in the operation itself to minimize these changes. Reconstructive surgery may be an option to restore tissues removed or altered by surgery.

Removal of tissues and the resulting scars can cause problems with the normal functions of the mouth and throat. These disruptions may be either temporary or permanent. Chewing, swallowing, and speaking are the functions most likely to be disrupted.

After surgery, the patient will see the surgeon, radiation oncologist, or both if he or she has received chemotherapy. The patient will also follow-up with the medical oncologist.

The patient will also continue to see the medical oncologist according to a schedule he or she will recommend. The patient may go through staging tests after completing treatment to determine how well the treatment worked and if he or she has any residual cancer. Thereafter, at regular visits, the patient will undergo physical examination and testing to make sure the cancer has not come back and that a new cancer has not appeared. At least five years of follow-up care is recommended, and many people choose to continue these visits indefinitely. The patient should report any new symptoms to the oncologist immediately. The patient should not wait for the next visit. Speech and swallowing therapy will continue for as long as needed to restore these functions.

Targeted therapy, in which a drug is given that is specially designed to target molecules specific to the particular type of cancer, may be administered or combined with other therapies in some cases. Cetuximab and several other new treatments are available for targeted oral cancer therapy. These treatments are often used in conjunction with older forms of chemotherapy and radiation therapy. For example, Cetuximab (Erbitux) is an engineered antibody that binds to the epidermal growth factor receptor, a molecule important for cell growth. It was the first targeted therapy approved for oral cancer. Cetuximab binds to oral cancer cells and interferes with cancer cell growth and the spread of cancer. Cetuximab is given once a week in an injection through a vein (intravenous injection). It may cause certain unique side effects, including an acne-like rash. Today there are numerous other targeted agents being studied for use against squamous cell carcinomas of the head and neck, as well as against other forms of cancer which can arise elsewhere in the body.

The prognosis of oral cancer is dependent upon many factors, including the exact type and stage of the tumor, the type of treatment that is chosen, and the overall health status of the patient. The average five-year survival rate for all people who undergo treatment for head and neck cancer has been reported at approximately 61%. The five-year survival rate for people diagnosed with localized cancers of the oral cavity is about 82%. When the cancer has spread to distant sites, the five-year survival rate drops to about 33%. More accurate percentages and survival statistics depend on the tumor location, staging, type of treatment, and the presence of other medical conditions.

People with a mouth and throat cancer have a chance of developing another head and neck cancer or cancer in a neighboring region such as the voice box (larynx) or esophagus (the tube between the throat and the stomach). Regular follow-up examinations and prevention are extremely important.

The best way to prevent head and neck cancer is to avoid the risk factors.

• If the patient uses tobacco, he or she should quit. Substituting "smokeless" tobacco for smoking is not advised. Pipe and cigar smoking are not safer than cigarette smoking.
• If the patient drinks alcohol, he or she should do so in moderation. The patient should not use both tobacco and alcohol.
• If the patient works outdoors or is otherwise frequently exposed to sunlight (ultraviolet radiation), he or she should wear protective clothing that blocks the sun. Sunscreen should be applied to the face (including a lip balm with sunscreen) and the patient should wear a wide-brimmed hat any time he or she is outdoors.
• Sources of oral irritation, such as ill-fitting dentures, should be avoided. If the patient wears dentures, he or she should remove and clean them every day. A dentist should check their fit regularly.

The patient should eat a balanced diet to avoid vitamin and other nutritional deficiencies. He or she should make sure to eat foods with plenty of vitamin A, including fruits, vegetables, and supplemented dairy products.

The patient should ask his or her dentist or primary care professional to check their oral cavity and pharynx regularly to look for precancerous lesions and other abnormalities. The patient should report any symptoms such as persistent pain, hoarseness, bleeding, or difficulty swallowing.

Upon completion of cancer treatment, the patient should request a survivorship care plan. Such a plan will include a summary of the treatments that they received. It will also outline further recommended follow-up appointments, scans, and other tests anticipated. Living with cancer presents many new challenges for the patient and for his or her family and friends.

• The patient will probably have many worries about how the cancer will affect his or her ability to "live a normal life," that is, to care for family and home, to hold a job, and to continue the friendships and activities that he or she enjoys.
• Many people feel anxious and depressed. Some people feel angry and resentful; others feel helpless and defeated.

For most people with cancer, talking about their feelings and concerns helps.

• Friends and family members can be very supportive. They may be hesitant to offer support until they see how the patient is coping. The patient should not wait for them to bring it up. If the patient wants to talk about his or her concerns, let them know.
• Some people don't want to "burden" their loved ones, or they prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if the patient wants to discuss his or her feelings and concerns about having cancer. The doctor should be able to recommend someone.
• Many people with cancer are profoundly helped by talking to other people who have cancer. Sharing concerns with others who have been through the same thing can be remarkably reassuring. Support groups of people with cancer may be available through the medical center where the patient receives treatment. The American Cancer Society also has information about support groups all over the United States.

As with other types of cancers, some patients may be eligible to participate in a clinical trial as part of their treatment plan. These are medically supervised studies that evaluate new treatments or new combinations of treatments.