Key Terms: Biopsy.
Definition
Cancer of the mouth or the oral cavity and the oropharynx is referred to as oral cancer.
Description
Oral cavity describes a broad array of parts within the mouth including the lips, lining on the lips and cheeks referred to as buccal mucosa, teeth, tongue, floor of the mouth under the tongue, hard palate (which is the firm bony top of the mouth), and the gums. The oropharynx includes the back of the tongue, the soft palate, and the tonsils (fleshy part on either side of the mouth). There are glands through out the oral cavity that produce saliva that keep the mouth moist, known as salivary glands. The secretions from these glands called saliva aid in digesting the food.
Under normal circumstances, the oral cavity and oropharynx are comprised of several types of tissues and cells, and tumors can develop from any of these cells. These tumors may either be benign (they do not spread to the adjoining tissues), or the tumor may invade other tissues of the body. Any potential growth of a benign tumor into a cancerous (malignant) tumor is referred to as a precancerous condition. Leukoplakia or erythroplakia, which are abnormal areas in the oral cavity, may develop in many of the oral cancers as the first stage. Leukoplakia is a white area that is a benign condition, but approximately 5% of leukoplakias develop into cancer. Erythroplakia is a red bumpy area that bleeds when scraped, and has the potential to develop into cancer within 10 years if not treated.
Benign tumors are those that are not invasive and thus incapable of spreading. Examples of benign tumors of the oral cavity include keratocanthoma, leiomyoma, osteochondroma, neurofibroma, papilloma, schwannoma, and odontogenic tumors. These tumors are generally harmless and can be surgically removed. Recurrence of these tumors after surgical removal is very rare.
More than 90% of malignant tumors of the oral cavity and oropharynx are squamous cell carcinoma also referred to as squamous cell cancer. Squamous cells form the lining of the oral cavity and oropharynx and morphologically, they appear flat and scale-like. When the cancer cells appear just in the lining of the oral cavity, it marks the initial stages of the squamous cell cancer and is referred to as carcinoma in situ. Appearance of cancer cells on deeper layers of the oral cavity or oropharynx refers to invasive squamous cell cancer which is a more serious condition. Verrucous carcinomas are a type of squamous cell carcinoma that seldom metastasize but can spread to the adjoining tissues. Thus a surgeon might suggest removal of a wide area of surrounding tissues in addition to removing the cancerous tissue. The chances of developing a second cancer in the oral region (oral cavity or pharynx) at a later time during the life period is about 10-40%, thus necessitating thorough follow-up examinations. In addition, refraining from smoking and drinking will help to prevent the disease recurrence. Among other types of malignant tumors of the oral cavity are salivary gland cancers and Hodgkin's disease. The former affects the salivary glands present throughout the mucosal lining of the oral cavity and oropharynx. The latter is the cancer that develops in the lymphoid tissue of the tonsils and base of the tongue.
Demographics
The statistical survey on oral cancers reveals that more men are affected by the disease than women. The American Cancer Society has estimated that about 28, 260 new cases of oral cavity and pharyngeal cancers will be diagnosed in the United States in the year 2004. Of these, predictions are that 18,550 cases will occur in men and 9,710 in women. The estimates also suggest that about 7,230 Americans will die of cancer of the oral cavity or oropharynx in 2004. The incidence and the mortality rate have been directed toward a decreasing trend in the last 20 years. Studies on patient survival show that about 82% of patients diagnosed with oral cancer survive for more than a year, about 51% survive for five years and about 48% for 10 years.
Certain geographic differences affect the incidence of oral cavity cancers. Hungary and France show higher incidence of the disease as compared to the United States. However, the disease is much less common in Japan and Mexico suggesting that environmental factors do play a key role in the outcome of the disease.
About 15% of patients diagnosed with either oral or oropharynx cancer are more often known to develop cancer of the adjoining organs (or tissues) including larynx, oesophagus or lung. The chances of developing a second cancer in the oral region (oral cavity or pharynx) for survivors, at a later time during the life period is about 10% to 40%. Thus, a person once diagnosed with cancer of oral cavity has to undergo through follow up examinations for the rest of his or her life, even if cured completely. In addition, restraining from smoking tobacco and drinking alcohol will greatly facilitate in preventing the disease occurrence as tobacco use has been shown to be responsible for 90% of tumors of oral cavity in men and 60% among women.
Causes and Symptoms
The major risk factors for oral and oropharyngeal cancers are smoking and alcohol consumption. These two factors account for 75% of all the oral cavity cancers reported in the United States. Smokeless tobacco (chew or spit tobacco) is yet another important cause for oral cancers. Each dip or chew of tobacco has been shown to contain 5 times more nicotine than one cigarette and 28 potential carcinogens. For lip cancer, exposure to sun may be one of the risk factors. Geographical factors and sexual differences also attribute to the risk factors of oral cancers. Men are twice as susceptible to oral cancers than women. While oral cancer is ranked sixth leading cancer among men in the United States, it is the fourth leading cancer in African American men. Age also seems to be a factor in the susceptibility of oral cancer. About 95% of oral cancer cases are diagnosed in people older than 45 years and the median age for diagnosis is 64 years. In addition to these factors, genetic predisposition may be one of the factors that should not be ignored in any type of cancer.
Many of the symptoms listed below may be of a less serious nature or related to other cancers. Common symptoms include:
- mouth sores that do not heal
- persistent pain in the mouth
- thickening in the mouth
- white or red patch on tongue, gums, tonsils or lining of the mouth
- sore throat
- difficulty in chewing or swallowing
- difficulty moving the jaw or tongue
- numbness of gums, tongue or any other area of the mouth
- swelling of the jaw
- loosening of the teeth
- voice changes
- weight loss
- feeling of lumpy mass in the neck
Any of the above symptoms that persists for more than a few weeks needs prompt medical attention.
Diagnosis
Routine screening or examination of oral cavity by a physician or a dentist is the key for early detection of oral and oropharyngeal cancers. Thorough self-examination is also highly recommended by physicians that may lead to an early diagnosis of abnormal growth in the oral cavity or neck. If any of the signs outlined above suggests the presence of oral cancer, the physician may recommend additional tests or procedures to confirm the diagnosis. These may be one or more of the following factors.
Head and Neck Examination
In addition to thorough physical examinations, physicians attach special attention to the neck and head area. Highly sophisticated fiberoptic scopes are used to view the oropharynx after inserting a tube through the mouth or nose. Because of the risk of additional cancers in patients with oral cancers, other parts of the head and neck including nose, larynx, lymph nodes are carefully examined. Depending on the parts examined, the procedures are termed as pharyngoscopy, laryngoscopy or nasopharyngoscopy.
Panendoscopy
Depending on the risk factors, the surgeon may suggest further examination of oral cavity, oropharynx, larynx, esophagus, trachea and the bronchi. This overall examination called panendoscopy is done under general anesthesia to avoid discomfort to the patient and allow a thorough check-up of the neck and head regions. During this process, a biopsy of the suspected tissue is done to determine the severity of the cancer. The specimens used could be a scraping from the suspected area and smeared into a slide which is stained and viewed under the micro-scope. This technique is easy, inexpensive and offers information on the abnormal lesions. Incisional biopsy is the removal of a piece of small tissue from an area of the tumor. This is a relatively simple procedure and is performed either in the doctor's office or in the operating room depending upon the area of the tumor to be removed. The biopsy tissue samples are treated through various steps before the cells can be viewed under the microscope. Fine-needle aspiration (FNA) biopsy is the aspiration of fluid from a mass, lump or cyst in the neck. This would also include excisional biopsy. Depending upon the type of cells recognized in the aspiration, the pathologists can determine whether the cancer is related to neck or oral region or it has metastasized from a distant organ. FNA may also determine whether the neck mass is benign that resulted from any infection related to mouth or oropharynx.
Computed Tomography (or Computer Axial Tomography)
A sophisticated x-ray test that scans parts of body in cross-section. This procedure is carried out after administering a dye that can aid in locating abnormalities. This helps in judging the extent of cancer spread to lymph nodes, lower mandible and neck.
Magnetic Resonance Imaging (MRI)
This is used for evaluting soft tissue details such as the cancers of the tonsil and base of tongue and the procedure is governed by magnets and radio waves.
Panorex
This is a rotating x ray of upper and lower jawbones that determines changes that occur due to cancers in the oral cavity.
In addition to the imaging tests already noted, chest x rays help in checking for lung cancers in oral cancer patients with smoking habits. Barium swallow is a commonly performed series of x rays to assess the cancers of the digestive tract in patients with oral cancer. A radionulide bone scan may be suggested if there is concern that the cancer may have spread to the bones.
Other tests may include blood tests given to provide a complete blood analysis, including a determination of anemia, liver disease, kidney disease and RBC and WBC counts.
Treatment Team
Cancer care team typically involves physician specialists to include, surgeon (oral or neck and head surgeon), a dentist (in cases of oral cancers), a medical oncologist and a radiation therapist.
Clinical Staging, Treatments, and Prognosis
Clinical Staging
TNM system of the American Joint Committee on Cancer has been followed in staging the cancer in which the size (T), spread to regional lymph nodes (N) and Metastasis to other organs (M) are classified.
T Classification
- Tx: Information not known and thus tumor cannot be assessed.
- T0: No evidence of primary tumor.
- Tis: Carcinoma in situ which means the cancer has affected the epithelial cells lining the oral cavity or the oropharynx and the tumor is not deep.
- T1: Tumor 2 cm (1 cm equals 0.39 inches) or smaller.
- T2: Tumor larger than 2 cm but smaller than 4 cm.
- T3: Tumor larger than 4 cm.
- T4: Tumor of any size that invades adjacent structures like larynx, bone, connective tissues or muscles.
N Classification
- Nx: Information not known, cannot be assessed.
- N0: No metastasis in the regional lymph node.
- N1: Metastasis in one lymph node on the same side of the primary tumor and smaller than 3cm.
- N2: Divided into 3 subgroups. N2a is metastasis in one lymph node larger than 3cm and smaller than 6cm. N2b is metastasis in multiple lymph nodes on the same side of tumor, none larger than 6cm. N2c denotes one or more lymph nodes, may or may not be on the side of primary tumor, none larger than 6 cm.
- N3: Metastasis in lymph node larger than 6cm.
M Classification
- Mx: Distant metastasis cannot be assessed, information not known.
- M0: No distant metastasis.
- M1: Distant metastasis present.
Stage Grouping
- Stage 0 (carcinoma in situ): Tis, N0, M0
- StageI: T1, N0, M0
- Stage II: T2, N0, M0
- Stage III: T3, N0, M0 or T1, N1, M0 or T2, N1, M0 or T3, N1, M0
- Stage IVA: T4, N0, M0 or T4, N1, M0 or Any T, N2, M0
- Stage IVB: Any T, N3, M0
- Stage IVC: Any T, any N, M1
Treatments
After the cancer is diagnosed and staged, the medical team dealing with the case will discuss the choice of treatment. This may be chemotherapy alone or in combination with radiation therapy or surgery. The treatment option is made depending upon the stage of the disease, the physical health of the patient, and after discussing the possible impact of the treatment on speech, swallowing, chewing, or general appearance.
Surgery
Primary tumor resection involves removal of the entire tumor with some normal adjacent tissue surrounding the tumor to ensure that all of the residual cancerous mass is removed. Partial mandible resection is carried out in cases where the jaw bone is suspected to have been invaded but with no evidence from x ray results. Full mandible resection is performed when the x rays indicate jaw bone destruction.
Maxillectomy is the removal of the hard palate if that is affected. A special denture called a prosthesis can alter the defect caused in the hard palate resulting from the surgery. Moh's surgery involves removal of thin sections of lip tumors. Immediate examination of the sections for potential cancer cells allows the surgeons to decide whether or not the cancer is completely removed.
Laryngectomy is the surgical removal of larynx (voice box). This is done when there is risk of food entering the trachea and infecting the lungs, as a result of removal of tumors of tongue or oropharynx. By removing the larynx, the trachea is attached to the skin of the neck thus eliminating the risk of infecting the lung and potential pneumonia.
Neck dissection is a surgical procedure involving removal of lymph nodes in the neck that are known to contain cancer cells. The side effects of this surgery include numbness of the ear, difficulty in raising the arm above the head, discomfort to the lower lip—all of which are caused by different nerves involved in the surgery.
Tracheostomy is an incision made in the trachea to facilitate breathing for oral cancer patients who may develop considerable swelling following surgical removal of the tumor in oral cavity. This prevents any obstruction in the throat and allows easy breathing.
In addition to the those surgical procedures, dental extractions and removal of large tumors in oral cancer patients may need reconstructive surgeries which may vary from one patient to the other depending upon the site and size of the tumors.
RADIATION THERAPY Use of high-energy rays to kill the cancer cells or reduce their growth is radiation therapy. It may be given as the only treatment of small tumors or given in combination with surgery to destroy deposits of cancer cells. Radiation is also suggested for relieving symptoms of cancer including difficulty in swallowing and bleeding. Radiation may be externally or internally administered. External radiation (also called external beam radiation therapy) delivers radiation to oral or oropharyngeal cancers from outside the body. Brachytherapy or internal radiation involves the surgical implant of metal rods that deliver radioactive materials in or near the cancer.
CHEMOTHERAPY Chemotherapy involves administering of anticancer drugs parenterally or orally. Chemotherapy may be suggested in combination with radiation therapy to avoid surgery in some large tumors of head and neck region. Some studies reveal that chemotherapy is ideal for shrinking the size of the tumor before surgery or radiation therapy is initiated. This is termed neoadjuvant chemotherapy.
Treatment Choices By Stage and Prognosis
Depending on the stage of cancer spread, different treatment options are recommended for oral cancer.
Stage 0: Surgical stripping or thin resection is suggested at this stage where the cancer has not become invasive. If there is repeated recurrence, radiation therapy is an option. More than 95% of the patients at this stage survive for long-term without the requirement of any surgery of their oral cavity.
Stages I and II: Surgery or radiation therapy is the choice of treatment depending on the location of the tumor in the oral cavity and oropharynx.
Stages III and IV: A combination therapy of either surgery and radiation or radiation and chemotherapy or all the three types of treatment may be required for these advanced stages of cancer. About 20% to 50% of patients undergoing a combination of surgery and radiation for stages III and IV oral cavity and oropharyngeal cancers have the chances of five-year disease free survival.
Alternative and Complementary Therapies
Various alternative medications are being tried periodically. While choosing any alternative therapy, a thorough discussion of the advantages and disadvantages of the suggested therapy with the medical team is highly recommended.
As of 2000, researchers had demonstrated that Bowman-Birk inhibitor, a protein found in soybeans shrinks leukoplakia or the precancerous growth in the mouth. The study has pointed to a reduction in the size of the leukoplakia to a third or half of the original size when the protein is orally administered for a month. The studies also suggest that a combination of soybean intake and termination of smoking tobacco will have a cumulative effect in the shrinking of leukoplakia. However, a thorough investigations in a larger patient population is necessary to confirm the therapeutic utility of the soybean protein in oral cancer.
Coping With Cancer Treatment
Cancer of any type is a psychologically distressful journey from the time of diagnosis, treatment and recovery. Coping with the side effects of treatment both physically and emotionally is a challenge to the patient, the family and the medical team. Oral cancers are further complicated by the fact that surgery most often leads to disfigurement which may be devastating in a society where importance is attached to physical appearance. Reconstruction surgeries or facial prostheses may be psychologically helpful and the cancer care team may advise on this issue. Laryngectomy or removal of the voice box leaves the person without speech, and breathing through stoma (in the neck). A stoma cover helps in hiding the mucus that the stoma secretes and also serves as a filter in the absence of nose's natural filter. The odors from the stoma can be prevented by use of cologne, and by avoiding strongly scented foods such as garlic. Studies reveal that lack of normal speech has a serious impact on sexual activity in couples. In addition to laryngectomy, surgery on the jaw, plate or tongue can also disrupt speech. These problems need to be discussed with the cancer care team or contact organizations such as the American Cancer Society who could provide relevant information on coping with specific issues on oral cancers.
Side effects of chemotherapy such as fatigue and hair loss (alopecia) may affect the quality of life in a patient. A wig may be used for cosmetic purposes that can hide the hair loss. Studies have shown that patients may gradually regain their health after chemotherapy if they abstain from smoking and drinking.
Clinical Trials
Evaluation of a potential treatment method for a disease on aselected patient population is called a clinical trial. Some of the ongoing clinical trials include:
- Paclitaxel and cisplatin for Stage III and IV of squamous cell carcinoma of the oral cavity following radiotherapy.
- Phase I study of intratumoral EGFR antisense DNA and DC chol liposomes in patients with advanced squamous cell carcinoma of oral cavity.
- Phase I immunotoxin therapy (PE38 immunotoxin) in treating patients with advanced lip and oral cavity cancer.
- Phase III megestrol acetate administration to patients undergoing cancer treatment for lip, oral cavity, and oropharyngeal cancers. This drug improves appetite and thus may prevent weight loss in cancer patients.
- Phase I combination of chemotherapy and radiation therapy in treating Stage III/IV lip, oral cavity, and oropharyngeal cancer. The drug tested is docetaxel.
Resources regarding these clinical trials, as well as many others regarding oral cancers, including any recruiting of patients for the trial are available at
Prevention
Oral cavity and oropharyngeal cancer patients are at risk for recurrences, or for developing secondary cancers in the head and neck area. Thus a close follow-up is mandatory in the first couple of years following the indicence. A thorough examination every month in the first year, and at least every three months during the following year, and each year thereafter is the recommended schedule to facilitate early detection, if any. Various chemopreventive drugs are being tested to prevent the occurrence of secondary tumors in the neck and head region. Vitamin A analog is one such chemopreventive drug under investigation that may help in suppressing the tumor formation.
Tobacco (smoking, chewing, spitting) and alcohol consumption are the major causes of oral and oropharyngeal cancers. Public knowledge regarding the risk factors of the oral cancers and the signs of early detection is limited. Only 25% of U.S. adults can detect early signs of abnormal oral cavity; and only 13% understand the implications of regular alcohol consumption in developing oral cancer. Cancer prevention and control programs are growing rapidly with screening services for high risk opulation, health promotion, education and intervention strategies. National Spit Tobacco Education Program (NSTEP), an initiative of Oral Health America, has been educating the public about dangers of spit tobacco and oral cancer.
Exposure to sun may cause lip cancers. Use of a lip balm will protect the lip from the sun rays. In addition, pipe smokers are more at risk for lip cancers.
Special Concerns
Surgery for oral cancer treatment may affect normal speech and swallowing. A speech pathologist will educate, and suggest remedies for restoring speech and swallowing problems. In addition, a dietitian may be consulted for choosing the more palatable food in the advent of chewing and swallowing problems. In case of dryness, a saliva supplement can be recommended by a physician.
Questions to Ask the Doctor
- What is oral cavity or oropharyngeal cancer?
- What is the extent of cancer spread beyond the primary site?
- What is the stage, and the severity of the stage?
- What are the treatment options available?
- What are the chances of survival, and the time frame of survival?
- What are the side of effects of treatment?
- What are the potential risks of specific treatments?
- How long will it take to recover from treatment?
- What are the chances of recurrence?
- What is the benefit of one treatment over the other in terms of recurrence?
- How to get ready for the treatment?
- Discuss the possibility of getting a second opinion.
Advances in reconstructive surgery of the mouth and lower face in the early 2000s have significantly improved patients' appearance and quality of life after treatment for oral cancer.
The side effects of cancer treatment will make the patient fatiqued. Giving ample time to recover will help improve energy for the long-term. Smoking cessation and elimination of alcohol, and maintaining a balanced diet with fruits, vegetables, and whole grain are key to returning to a normal life for patients suffering from oral cancers.
Resources
Books
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Disorders of the Oral Region: Neoplasms." Section 9, Chapter 105 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Periodicals
Oliver, R. J., P. Sloan, and M. N. Pemberton. "Oral Biopsies: Methods and Applications." British Dental Journal 196 (March 27, 2004): 329–333.
Palme, C. E., P. J. Gullane, and R. W. Gilbert. "Current Treatment Options in Squamous Cell Carcinoma of the Oral Cavity." Surgical Oncology Clinics of North America 13 (January 2004): 47–70.
van de Pol M., P. C. Levendag, R. R. de Bree, et al. "Radical Radiotherapy Compared with Surgery for Advanced Squamous Cell Carcinoma of the Base of Tongue." Brachytherapy 3 (February 2004): 78–86.
Organizations
American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). 310 South Henry Street, Alexandria, VA 22314. (703) 299-9291.
American Society of Plastic Surgeons (ASPS). 444 East Algonquin Road, Arlington Heights, IL 60005. (847) 228-9900.
Support for People with Oral and Head and Neck Cancer (SPOHNC). P.O. Box 53, Locust Valley, NY 11560-0053. (800) 377-0928.
Other
American Cancer Society (ACS). Cancer Facts & Figures 2004.
"Chemical Found in Soybeans May Help Prevent Oral Cancer." American Cancer Society. [cited July 5, 2005].
"Oral and Oropharyngeal Cancers: Clinical Trials" National Institutes of Health. [cited July 5, 2005].
"Oral Cancer." National Cancer Institute. [cited July 5, 2005].
—Kausalya Santhanam, Ph.D.; Rebecca J. Frey, Ph.D.
