Background

Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers.

Methods

This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross-tabulations, and relative survival was used to calculate outcome

Results

Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non-SCC, and this was related to survival in these patients. African-Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced-stage SCC. Five-year relative survival for SCC cases was lower for older patients, men, and African-Americans.

Conclusions

This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States. © 2002 John Wiley & Sons, Inc.

What is oral cancer?

Cancer is defined as the uncontrollable growth of cells that invade and cause damage to surrounding tissue. Oral cancer appears as a growth or sore that does not go away. Oral cancer — which includes cancers of the lips, tongue, cheek, floor of the mouth, hard and soft palate, sinuses, and pharynx (throat) — can be life-threatening if not diagnosed and treated early.

What are the signs and symptoms of oral cancer?

The following are the common signs and symptoms:

•           Swellings/thickenings, lumps or bumps, rough spots/crusts/or eroded areas on the lips, gums, or other areas inside the mouth

•           The development of velvety white, red, or speckled (white and red) patches in the mouth

•           Unexplained bleeding in the mouth

•         Unexplained numbness, loss of feeling, or pain/tenderness in any area of the face, mouth, or neck

•           Persistent sores on the face, neck, or mouth that bleed easily and do not heal within two weeks

•           A soreness or feeling that something is caught in the back of the throat

•           Difficulty chewing or swallowing, speaking, or moving the jaw or tongue

•           Hoarseness, chronic sore throat, or changes in the voice

•           Ear pain

•           A change in the way your teeth or dentures fit together – a change in your “bite”

•           Dramatic weight loss

If you notice any of these changes, contact your dentist immediately for a professional examination.

I recently noticed a whitish patch in my mouth. Is this oral cancer?

This whitish patch could be leukoplakia. Leukoplakia, a condition caused by excess cell growth, can form on the cheeks, gums, or tongue. Leukoplakia is commonly seen in tobacco users, in people with ill-fitting dentures, and in those who have a habit of chewing on their cheek. This condition can progress to cancer. Red patches in the mouth (called erythroplakia) are less common than leukoplakia but have an even greater potential for being cancerous. Any white or red lesion in your mouth should be evaluated by your dentist.

Who gets oral cancer and what are the risk factors for oral cancer?

According to the American Cancer Society, men face twice the risk of developing oral cancer as women, and men who are over age 50 face the greatest risk. The rate of development of cancer of the oral cavity and pharynx began to decline in the late 1970s and has continued to decline throughout the 1990s in both African Americans, and white males and females.

Risk factors for the development of oral cancer include:

•     Cigarette, cigar, or pipe smoking — Smokers are six times more likely than non-smokers to develop oral cancers.

•          Use of smokeless tobacco products (for example, dip, snuff, or chewing tobacco) — Use of these products increase the risk of cancers of the cheek, gums, and lining of the lips.

•           Excessive consumption of alcohol — Oral cancers are about six times more common in drinkers than in non-drinkers.

•           Family history of cancer

•           Excessive exposure to the sun — especially at a young age

It is important to note that more than 25% of all oral cancers occur in people who do not smoke and who only drink alcohol occasionally.

How is oral cancer diagnosed?

Your dentist will conduct an oral cancer screening exam, which is a routine part of a comprehensive dental examination. More specifically, your dentist will feel for any lumps or irregular tissue changes in your neck, head, face, and oral cavity. When examining your mouth, your dentist will look for any sores or discolored tissue, as well as check for or ask you about the signs and symptoms mentioned above.

Your dentist might perform an oral brush biopsy if he or she sees tissue in your mouth that looks suspicious. This test is painless and involves taking a small sample of the tissue and analyzing it for abnormal cells. Alternatively, if the tissue looks even more suspicious, your dentist might recommend a scalpel biopsy. This procedure usually requires local anesthesia and might be performed by your dentist or a specialist referred by your dentist. These tests are necessary to detect oral cancer early, before it has had a chance to progress and spread.

How is oral cancer treated?

Oral cancer is treated the same way many other cancers are treated; that is with surgery to remove the cancerous growth followed by radiation therapy and/or chemotherapy (drug treatments) to destroy any remaining cancer cells.

What can I do to prevent oral cancer?

You can take an active role in preventing oral cancer or detecting it early, should it occur.

•           Conduct a self exam at least once a month. Using a bright light and a mirror, look and feel your lips and front of your gums. Tilt your head back and look at and feel the roof of your mouth. Pull your checks out to view the inside of your mouth, the lining of your cheeks, and the back gums. Pull out your tongue and look at all surfaces. Examine the floor of your mouth. Look at the back of your throat. Feel for lumps or enlarged lymph nodes in both sides of your neck and under your lower jaw. Call your dentist’s office immediately if you notice any changes in the appearance of your mouth or any of the signs and symptoms mentioned above.

•           See your dentist on a regular schedule. Even though you might be conducting frequent self exams, sometimes dangerous spots or sores in the mouth can be very tiny and difficult to see on your own. The American Cancer Society recommends oral cancer screening exams every three years for people over age 20 and annually for those over age 40. During your next dental appointment, ask your dentist to perform an oral exam. Early detection can improve the chance of successful treatment.

•           Don’t smoke or use any tobacco products and drink alcohol in moderation. (Refrain from binge drinking.)

•           Eat a well balanced diet.

•          Limit your exposure to the sun. Repeated exposure increases the risk of cancer on the lip, especially the lower lip. When in the sun, use UV-A/B-blocking sun protective lotions on your skin as well as your lips.

Lung, oropharyngeal and oral cavity cancer are the most common cancer sites observed by Indian registries.1 These cancer sites are causally related to the use of tobacco in different forms.2 In India, the use of tobacco is common in the form of chewing and smoking of bidis and cigarettes.3

Two studies are available from India on the role of bidi smoking in the development of lung cancer.4,5 A few studies, mainly from West Maharashtra and South India, have reported the risk of oropharyngeal and oral cavity cancer and smoking and oral use of tobacco,6,7,8 but no study has been reported from central India.

In the present study three cancer sites (lung, oropharynx and oral cavity) were investigated using a common protocol and data from the Bhopal Cancer Registry. The risk of tobacco use, particularly bidi smoking and chewing, was estimated for these three sites. A study on tobacco use in this population is particularly important as it suffered exposure to methyl-isocyanate gas due to a chemical accident in 1984 and thus is different from other parts of the world.

 

The present study examines data for the three most common cancer sites in males (lung, oropharynx and oral cavity), collected by the Bhopal Population-Based Cancer Registry during the years 1986–1992.

The cancer cases were coded by four-digit International Classification of Diseases for Oncology (ICD-O) code.9 The cancer sites included under oropharynx were posterior third of tongue (141.0 and 141.6), soft palate (145.3), uvula (145.4), oropharynx (146.0–146.9), nasopharynx (147.0–147.9), and hypopharynx (148.0–149.0). The cancer sites included under oral cavity were lip (140.0–140.9), anterior two-thirds of tongue (141.1–141.5), gingivum (143.0–143.9), floor of mouth (144.0–144.9), cheek mucosa (145.0–145.2), hard-palate and retromolar area (145.5–145.9). A total of 260 controls were randomly sampled from a total of about 2500 males surveyed for tobacco habits in the Bhopal population. This tobacco survey was based on random samples from the voter list of the Bhopal municipal corporation area. The survey was conducted by the Bhopal cancer registry during 1989–1992. The controls were not matched for age with the cases, however, they were age-stratified and then randomly selected to follow the age distribution of cases.

The cases and controls were interviewed according to a precoded questionnaire. The subjects were asked about identification particulars, socioeconomic parameters, tobacco habits, and clinical history. The interview was conducted by three qualified social workers of the Cancer Registry staff. The cases for which detailed information about smoking or chewing history were not available were excluded from the study. Cases registered from death certificates were excluded. Similarly, the tongue not otherwise specified cases (141.9) were not included in the analysis. After exclusion, a total of 163 lung, 247 oropharyngeal and 148 oral cavity cancer cases were available for the analysis.

The data collected were compiled and quality checks were carried out. Age-adjusted odds ratio (OR) and 95% CI for the sites under study according to religion, educational status, smoking and chewing habits were estimated using unconditional multiple logistic regression models. The models were compared using the differences in deviance and in degrees of freedom. The result of variable of interest with and without confounding variable was tabulated. The effect of interaction between variable of interest and confounder were also obtained to understand the validity of adjustment. The dummy variable and linear dose-response model was compared for testing the extent to which the linear trend adequately explains the variation between the dose level.10 The population attributable risk and attributable risk of individuals exposed to exposure of interest were also estimated. For model fitting, the statistical program GLIM was used.11

 presents the distribution of socio-demographic, smoking and chewing habits for lung, oropharyngeal and oral cavity cancer cases and controls. Most of the cases and controls were Hindu. Of the controls, 51.5% never had formal education, while 53.4% of lung, 64% of oropharyngeal and 70.9% of oral cavity cancer cases had never attended the school. The habit of smoking and tobacco chewing was more common among cases than the controls.

The multiplicative interaction between bidi and cigarette smoking was significant at the 5% level: the risk of bidi and cigarette smoking combined was observed to be 24.1 and 6.2 for lung and oropharyngeal cancer, respectively, in comparison to non-smokers of bidi and cigarettes. The risk of developing lung cancer (11.6/7.7 = 1.5) and oropharyngeal cancer (7.9/4.1 = 1.9) was higher for bidi smokers in comparison to cigarette smokers

           

The risk of lung and oropharyngeal cancer increased approximately more than four and three times, respectively, within three levels of grouping done for duration of smoking of bidi/cigarettes. The risk of getting oral cavity cancer was 4.3 for those who had smoked for >30 years compared to non-smokers. The risk of >500 cumulative years of tobacco smoked compared to non-smokers was 67.6 for lung cancer, 23.0 for oropharyngeal cancer and 6.0 for oral cavity cancer. The lung cancer risk according to histological types among smokers compared to non-smokers shows that the risk is higher for squamous cell carcinoma. The OR estimates for small cell and oat cell carcinoma were based on small numbers and no convergence was obtained for this type. The risk among smokers by histological types was not estimated for oropharyngeal and oral cavity cancer as only one case of adenocarcinoma was reported for oropharyngeal cancer while for the oral cavity only squamous cell carcinomas were reported during the study period.

The motivation for examining the carcinogenic effects of tobacco smoking and chewing in this population was that smoking habits differ in India and in this region from other parts of the world. The habit of bidi smoking and ‘zarda’, a form of tobacco chewing, is peculiar to this region. Case ascertainment in the present study is based on Cancer Registry data and thus entailed high-quality diagnostic confirmation. The controls were randomly selected from a tobacco survey conducted in the same population. Although the controls were not selected concurrently with the cases, it seems unlikely that this will alter the risk estimates as the period of survey (1989–1992) was almost same as the recruitment of cases (1986–1992) for the study. Further, no anti-tobacco activities were organized during the study period to alter the prevalence of tobacco habits in this population.

Religion and educational status were not observed to be risk factors in the present study. A study of the association of religion and smoking habits with lung cancer likewise did not observe any excess risk for different religion.5 Both bidis and cigarettes were found to be independently associated with increased risk of lung and oropharynx cancer. Two previous studies on the risk of lung cancer among bidi smokers have shown conflicting results. Notani and Sanghavi,4 taking hospital controls, found a relative risk of 2.6, while Jussawalla and Jain,5 taking community controls, found a relative risk of 19.3 in comparison to non-smokers. Similar to the present study increased risk for oropharyngeal cancer among bidi smokers was observed in a previous study.6

The observed OR for bidi and cigarette smoking combined (OR = 24.1 for lung and OR = 6.2 for oropharynx) in comparison to non-smokers of both was much lower than expected, indicating that either mode of action is not multiplicative or those smoking both bidis and cigarettes are light smokers of each.

Chewing tobacco contains a high level of TSNA.13 Of these, for NNK and its reduction product 4-(methyal(nitrosoamino)-1-1(3-pyridyl)-1-butanol) (NNAL) the major target organ is the lung, especially the peripheral part of the lung. This is independent of the route of admission, whether these procarcinogens are applied topically to the skin, taken orally or by intraperitoneal injection.16,17 These experimental studies suggest that tobacco chewing may also enhance the risk of lung cancer. The present study, however, did not observe any increased risk of tobacco chewing for lung cancer. The increased risk for oral cavity cancer among tobacco chewers is in accordance to that observed by other workers.7,8,18 These risk estimates in the present study could not be adjusted for the use of alcohol as history of alcohol use was not taken in the Cancer Registry proforma. However, this does not seem to alter the risk of tobacco chewing to a great extent. In India the prevalence of alcohol consumption particularly relative to tobacco chewing is low. Studies from India have not observed excess risk for oral cancer among alcohol users.

 Of action of tobacco quid chewing and smoking may not be multiplicative. It further indicated a decline in risk of chewing of tobacco with increased amount of tobacco smoked, this may be because heavy smokers chew less than light smokers.

In India cross-sectional surveys have shown that the percentage of people who chew betel quid without tobacco is small. In the present study also, based on small numbers, elevated risk was observed for oral cavity cancer among chewers not using tobacco, a finding similar to another study from south India.8

Tobacco consumption has decreased in many developed countries while in most developing countries it is still increasing. This may largely be due to the fact that relatively fewer studies have been reported from developing countries, including India, on the risk of cancer at different cancer sites due to the use of various forms of tobacco.19 In the present study it was estimated that the population attributable risk per cent (PARP) for smoking was quite high for lung (82.7%) and oropharyngeal cancer (71.6%). Similarly, the PARP was found to be 66.1% for tobacco chewers for development of oral cavity cancer. The attributable risk among smokers was observed to be 92% and 85% for lung and oropharyngeal cancer, respectively. The attributable risk for those who chewed tobacco was 84.4% for development of oral cavity cancer. This suggests that the high percentage of lung, oropharyngeal and oral cavity cancers in Bhopal could be prevented if tobacco habits were not started. Intervention studies encouraging quitting tobacco use have much relevance in Bhopal as in this population lungs are already damaged to some extent due to exposure to methyl isocynate gas as a result of the chemical disaster in December 1984. Even if gas exposure proves to be carcinogenic in future, by preventing the use of tobacco, a large number of cancer cases could be prevented.

 

The authors would like to thank the staff of the Bhopal Cancer Registry. The helpful advice of Dr Matti Hakama and Dr Suvi Virtanen is gratefully acknowledged. The Bhopal Cancer Registry is a part of and funded by National Cancer Registry Programme of Indian Council of Medical Research.

If an abnormal area has been found in the oral cavity, a biopsy is the only way to know whether it is cancer. Usually, the patient is referred to an oral surgeon or an ear, nose, and throat surgeon, who removes part or all of the lump or abnormal- looking area. A pathologist examines the tissue under a microscope to check for cancer cells.

Almost all oral cancers are squamous cell carcinomas. Squamous cells line the oral cavity.

If the pathologist finds oral cancer, the patient’s doctor needs to know the stage, or extent, of the disease in order to plan the best treatment. Staging tests and exams help the doctor find out whether the cancer has spread and what parts of the body are affected.

Staging generally includes dental x-rays and x-rays of the head and chest. The doctor may also want the patient to have a CT (or CAT) scan. A CT scan is a series of x-rays put together by a computer to form detailed pictures of areas inside the body. Ultrasonography is another way to produce pictures of areas in the body. High-frequency sound waves (ultrasound), which cannot be heard by humans, are bounced off organs and tissue. The pattern of echoes produced by the waves creates a picture called a sonogram. Sometimes the doctor asks for MRI (magnetic resonance imaging), a procedure in which pictures are created using a magnet linked to a computer. The doctor also feels the lymph nodes in the neck to check for swelling or other changes. In most cases, the patient will have a complete physical examination before treatment begins.

Our clinics are the world’s largest cancer treatment centre using alternative medicine or Homeopathy. Almost all variants of the disease are treated here in the thousands. As there are no other forms of people getting to know about our cancer treatment successes, we have found that almost all cancer patients visiting us are doing so because they are personally aware of another patient suffering from cancer or similar life threatening disease.

 

This is the disease that is receiving the maximum attention of Researchers in Medicine. Literally millions of academic papers have been published on the subject and countless Billions of Dollars have been invested in research. Yet unfortunately, very little progress is being seen on the ground using conventional medicine so far.

 

Our experience as demonstrated in a very few randomly selected cases, is that compared to conventional therapies (normally chemo therapy or radiotherapy) they live better, longer and even have the highest chance of becoming free from the disease completely. Another factor that is important for a country like India, Africa, Latin American countries is that the cost of pursuing this form of treatment is significantly lower inspite of these distinct advantages over conventional medicine.

 

Another vital feature of our treatment is that our treatment can be used even when the health of the patient is too frail to be subjected to Chemo, Radiotherapy or Surgery. This is because unlike the conventional medicine treatment options our medicines do not have any side-effects at all and can be confidently used in every state of the patient’s health.

Our Approach to Treatment:

We now have standardised treatments that are specific for each type of cancer that we have found to act in most of the cases. In those minorty of the cases where the patient fails to respond to these standardised treatment procedures we need to adopt a more individualistic approach.

 

We have two simultaneous lines of medication. One set addresses the immediate concerns of the patient - like pains, water accumulation, nausea, Insomnia (sleeplessness) etc. The other line of medication is targeted at the main disease itself. A lot of research effort has been put into Cancer Pain management and as a result again there is a group of medicines identified by us which enables us to address the severe pains experienced by cancer patients.

 

The first line of treatment is aimed at improving the quality of life of the patient. The second line of treatment is for dealing with the main disease.

 

However, the procedures adopted are dependent on the exact symptoms of the disease

Click here to have a look at a randomly selected set of 48 successfully treated Cancer cases among the thousands that we have been treating successfully all these years.

 

The important thing is that most of them respond to the standardised treatment that has been created by the extensive research carried out over several decades by Dr. Parimal Banerji and his son Dr. Paramesh Banerji

From 1995 to 2002, a case-control study on food groups and risk of cancer of the oral cavity and pharynx was conducted in Montevideo, Uruguay. Two hundred thirty cases were frequency-matched to 460 controls on age, residence, and urban/rural status. The study was restricted to men. The relationship between foods and risk of oral and pharyngeal squamous cell carcinoma was examined through: 1) individual food group analysis, 2) factor analysis, and 3) determination of empirical scores. The results were similar. Factor analysis generated 2 patterns, which were labeled as “stew” and “vegetables and fruits.” The stew pattern loaded positively on boiled meat, cooked vegetables, potato, and sweet potato. This pattern was directly associated with risk of oral and pharyngeal cancer [odds ratio (OR), 3.75; 95% confidence interval (CI), 1.99-7.06; P value for trend=0.0002]. The vegetables and fruits factor loaded positively on raw vegetables, citrus fruits, other fruits, liver, fish, and desserts. This pattern was inversely associated with risk of oropharyngeal carcinoma (OR, 0.34; 95% CI, 0.18-0.64; P value for trend=0.0008). Joint effects of high intake of risk foods and low intake of protective foods were associated with a risk of 12.0 (95% CI, 4.1-34.6). Our study confirms the important role of dietary factors in oral and pharyngeal cancer risk and suggests that the analysis of dietary patterns is a powerful tool to investigate the links between nutrition and cancer.

The oral cavity is a very specific place, well defined and broken down into various sites.  The reason for this is that the treatment and prognosis for each site can vary tremendously, depending on the size and extent of the tumor.  For the purposes of this discussion, I will actually include some sites that are, strictly speaking, not actually part of the oral cavity, such as the tonsil, soft palate, and base of tongue.  These are actually parts of what is called the oropharynx, or upper throat.  I do this because most people would think that any tumor you can see with the mouth open is in the mouth.  As simple an explanation as that is, it is not exactly correct from a scientific point of view.

There are a number of different cancers that can be found in the oral cavity.  The most common is one called Squamous Cell Carcinoma (cancer) and it is almost always, but not always, associated with smoking and drinking.  This is a cancer that begins in the cells of the lining of the mouth and upper respiratory and digestive tract.  We will focus on this one because it is the most common.  Another source of cancer in the mouth is the minor salivary glands that are found there just underneath the surface.  These cancers are usually what are called adenocarcinoma or some variation of adenocarcinoma and are much less common.   Finally, there are a number of other cancers of the oral vacity that are very uncommon and rare.

We will focus on Squamous Cell Cancer in the mouth and related places. For more information on oral cancer, please visit our site, www.tonguecancer.com

The oral cavity extends from the skin-vermilion junctions of the anterior lips to the junction of the hard and soft palates above and to the line of circumvallate papillae below and is divided into the following specific areas:

•           Lip.

•           Anterior two thirds of tongue.

•           Buccal mucosa.

•           Floor of mouth.

•           Lower gingiva.

•           Retromolar trigone.

•           Upper gingiva.

•           Hard palate.

The main routes of lymph node drainage are into the first station nodes (i.e., buccinator, jugulodigastric, submandibular, and submental). Sites close to the midline often drain bilaterally. Second station nodes include the parotid, jugular, and the upper and lower posterior cervical nodes.

Early cancers (stage I and stage II) of the lip and oral cavity are highly curable by surgery or by radiation therapy, and the choice of treatment is dictated by the anticipated functional and cosmetic results of treatment and by the availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient. [1] [2] [3] The presence of a positive margin or a tumor depth of more than 5 mm significantly increases the risk of local recurrence and suggests that combined modality treatment may be beneficial. [4] [5]

Advanced cancers (stage III and stage IV) of the lip and oral cavity represent a wide spectrum of challenges for the surgeon and radiation oncologist. Except for patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes larger than 2 cm, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. [2] Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials. Such trials evaluate the potential role of radiation modifiers or combination chemotherapy combined with surgery and/or radiation therapy.

Patients with head and neck cancers have an increased chance of developing a second primary tumor of the upper aerodigestive tract. [6] [7] A study has shown that daily treatment of these patients with moderate doses of isotretinoin (13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors. No survival advantage has yet been demonstrated, however, in part due to recurrence and death from the primary malignancy. Additional trials are ongoing. [8]

The rate of curability of cancers of the lip and oral cavity varies depending on the stage and specific site. Most patients present with early cancers of the lip, which are highly curable by surgery or by radiation therapy with cure rates of 90% to 100%. Small cancers of the retromolar trigone, hard palate, and upper gingiva are highly curable by either radiation therapy or surgery, with survival rates of as much as 100%. Local control rates of as much as 90% can be achieved with either radiation therapy or surgery in small cancers of the anterior tongue, the floor of the mouth, and buccal mucosa. [9]

Moderately advanced and advanced cancers of the lip also can be controlled effectively by surgery or radiation therapy or a combination of these. The choice of treatment is generally dictated by the anticipated functional and cosmetic results of the treatment. Moderately advanced lesions of the retromolar trigone without evidence of spread to cervical lymph nodes are usually curable and have shown local control rates of as much as 90%; such lesions of the hard palate, upper gingiva, and buccal mucosa have a local control rate of as much as 80%. In the absence of clinical evidence of spread to cervical lymph nodes, moderately advanced lesions of the floor of the mouth and anterior tongue are generally curable with survival rates of as much as 70% and 65%, respectively. [9] [10]

References:

1.         Cummings CW, Fredrickson JM, Harker LA, et al.: Otolaryngology - Head and Neck Surgery. Saint Louis, Mo: Mosby-Year Book, Inc., 1998.

2.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

3.         Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

4.         Jones KR, Lodge-Rigal RD, Reddick RL, et al.: Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity. Arch Otolaryngol Head Neck Surg 118 (5): 483-5, 1992.

5.         Po Wing Yuen A, Lam KY, Lam LK, et al.: Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck 24 (6): 513-20, 2002.

6.         Day GL, Blot WJ: Second primary tumors in patients with oral cancer. Cancer 70 (1): 14-9, 1992.

7.         van der Tol IG, de Visscher JG, Jovanovic A, et al.: Risk of second primary cancer following treatment of squamous cell carcinoma of the lower lip. Oral Oncol 35 (6): 571-4, 1999.

8.         Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.

9.         Wallner PE, Hanks GE, Kramer S, et al.: Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth. Am J Clin Oncol 9 (1): 50-7, 1986.

10.       Takagi M, Kayano T, Yamamoto H, et al.: Causes of oral tongue cancer treatment failures. Analysis of autopsy cases. Cancer 69 (5): 1081-7, 1992.

Cellular Classification

Most head and neck cancers are of the squamous cell variety and may be preceded by various precancerous lesions. Minor salivary gland tumors are not uncommon in these sites. Specimens removed from the lesions may show the carcinomas to be noninvasive, in which case the term carcinoma in situ is applied. An invasive carcinoma will be either well-differentiated, moderately well-differentiated, poorly differentiated or undifferentiated.

Tumor grading is recommended using Broder classification (Tumor Grade [G]):

•           G1: well-differentiated.

•           G2: moderately well-differentiated.

•           G3: poorly-differentiated.

•           G4: undifferentiated. [1]

No statistically significant correlation between degree of differentiation and the biologic behavior of the cancer exists; however, vascular invasion is a negative prognostic factor. [2]

Other tumors of glandular epithelium, odontogenic apparatus, lymphoid tissue, soft tissue, and bone and cartilage origin require special consideration and are not included in this section of PDQ. Reference to the World Health Organization nomenclature is recommended.

The term leukoplakia should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may only represent a fungal infection, lichen planus, or other benign oral disease.

References:

1.         Bansberg SF, Olsen KD, Gaffey TA: High-grade carcinoma of the oral cavity. Otolaryngol Head Neck Surg 100 (1): 41-8, 1989.

2.         Close LG, Brown PM, Vuitch MF, et al.: Microvascular invasion and survival in cancer of the oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg 115 (11): 1304-9, 1989.

Stage Information

The staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Information from diagnostic imaging studies may be used in staging. 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. [1] If a patient relapses, complete restaging must be done to select the appropriate additional therapy. [2] [3]

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification. [4]

TNM Definitions

Primary tumor (T)

•           TX: Primary tumor cannot be assessed

•           T0: No evidence of primary tumor

•           Tis: Carcinoma in situ

•           T1: Tumor no larger than 2 cm in greatest dimension

•           T2: Tumor larger than 2 cm but no larger than 4 cm in greatest dimension

•           T3: Tumor larger than 4 cm in greatest dimension

•           T4: (lip) Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose

o          T4a: (oral cavity) Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, and skin of face)

o          T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4.

Regional lymph nodes (N)

•           NX: Regional lymph nodes cannot be assessed

•           N0: No regional lymph node metastasis

•           N1: Metastasis in a single ipsilateral lymph node, no larger than 3 cm in greatest dimension

•           N2: Metastasis in a single ipsilateral lymph node, larger than 3 cm but no larger than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, no larger than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, no larger than 6 cm in greatest dimension

o          N2a: Metastasis in a single ipsilateral lymph node larger than 3 cm but no larger than 6 cm in dimension

o          N2b: Metastasis in multiple ipsilateral lymph nodes, no larger than 6 cm in greatest dimension

o          N2c: Metastasis in bilateral or contralateral lymph nodes, no larger than 6 cm in greatest dimension

•           N3: Metastasis in a lymph node larger than 6 cm in greatest dimension

In clinical evaluation, the actual size of the nodal mass should be measured and allowance should be made for intervening soft tissues. Most masses larger than 3 cm in diameter are not single nodes but are confluent nodes or tumors in soft tissues of the neck. The three stages of clinically positive nodes are: N1, N2, and N3. The use of subgroups a, b, and c is not required but is recommended. Midline nodes are considered homolateral nodes.

Distant metastasis (M)

•           MX: Distant metastasis cannot be assessed

•           M0: No distant metastasis

•           M1: Distant metastasis

AJCC Stage Groupings

Stage 0

•           Tis, N0, M0

Stage I

•           T1, N0, M0

Stage II

•           T2, N0, M0

Stage III

•           T3, N0, M0

•           T1, N1, M0

•           T2, N1, M0

•           T3, N1, M0

Stage IVA

•           T4a, N0, M0

•           T4a, N1, M0

•           T1, N2, M0

•           T2, N2, M0

•           T3, N2, M0

•           T4a, N2, M0

Stage IVB

•           Any T, N3, M0

•           T4b, any N, M0

Stage IVC

•           Any T, any N, M1

References:

1.         Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.

2.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

3.         Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

4.         Lip and oral cavity. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 23-32.

Treatment Option Overview

Depending on the site and extent of the primary tumor and the status of the lymph nodes, the treatment of lip and oral cavity cancer may be by surgery alone, radiation therapy alone, or a combination of these. Some general considerations are as follows. [1] [2] [3] [4] [5]

For lesions of the oral cavity, surgery must adequately encompass all of the gross as well as the presumed microscopic extent of the disease. If regional nodes are positive, cervical node dissection is usually done in continuity. With modern approaches, the surgeon can successfully ablate large posterior oral cavity tumors and with reconstructive methods can achieve satisfactory functional results. Prosthodontic rehabilitation is important, particularly in early-stage cancers, to assure the best quality of life.

Radiation therapy for lip and oral cavity cancers can be by external-beam radiation therapy (EBRT) or interstitial implantation alone, but for many sites the use of both modalities produces better control and functional results. Small superficial cancers can be very successfully treated by local implantation using any one of several radioactive sources, by intraoral cone radiation therapy, or by electrons. Larger lesions are frequently managed using EBRT to include the primary site and regional lymph nodes even if they are not clinically involved. Supplementation with interstitial radiation sources may be necessary to achieve adequate doses to large primary tumors and/or bulky nodal metastases. A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible. [6] [7]

Early cancers (stage I and stage II) of the lip, floor of mouth, and retromolar trigone are highly curable by surgery or radiation therapy. The choice of treatment is dictated by the anticipated functional and cosmetic results and by the availability of the particular expertise required of the surgeon or radiation oncologist for the individual patient. Advanced cancers (stage III and stage IV) of the lip, floor of mouth, and retromolar trigone represent a wide spectrum of challenges for the surgeon and radiation oncologists. Except for patients with small T3 lesions and no regional lymph node and no distant metastases or who have no lymph nodes larger than 2 cm, for whom treatment by radiation therapy alone or surgery alone might be appropriate, most patients with stage III or stage IV tumors are candidates for treatment by a combination of surgery and radiation therapy. Furthermore, because local recurrence and/or distant metastases are common in this group of patients, they should be considered for clinical trials evaluating the following: the potential role of radiation modifiers to improve local control or decrease morbidity; or, the role of combinations of chemotherapy with surgery and/or radiation therapy both to improve local control and to decrease the frequency of distant metastases.

Early cancers of the buccal mucosa are equally curable by radiation therapy or by adequate excision. Patient factors and local expertise influence the choice of treatment. Larger cancers require composite resection with reconstruction of the defect by pedicle flaps.

Early lesions (T1 and T2) of the anterior tongue may be managed by surgery or by radiation therapy alone. Both modalities produce 70% to 85% cure rates in early lesions. Moderate excisions of tongue, even hemiglossectomy, can often result in surprisingly little speech disability provided the wound closure is such that the tongue is not bound down. If, however, the resection is more extensive, problems may include aspiration of liquids and solids and difficulty in swallowing in addition to speech difficulties. Occasionally, patients with tumor of the tongue require almost total glossectomy. Large lesions generally require combined surgical and radiation treatment. The control rates for larger lesions are about 30% to 40%. According to clinical and radiological evidence of involvement, cancers of the lower gingiva that are exophytic and amenable to adequate local excision may be excised to include portions of bone. More advanced lesions require segmental bone resection, hemimandibulectomy, or maxillectomy, depending on the extent of the lesion and its location.

Early lesions of the upper gingiva or hard palate without bone involvement can be treated with equal effectiveness by surgery or by radiation therapy alone. Advanced infiltrative and ulcerating lesions should be treated by a combination of radiation therapy and surgery. Most primary cancers of the hard palate are of minor salivary gland origin. Primary squamous cell carcinoma of the hard palate is uncommon, and these tumors generally represent invasion of squamous cell carcinoma arising on the upper gingiva, which is much more common. Thus, management of squamous cell carcinoma of the upper gingiva and hard palate are usually considered together. Surgical treatment of cancer of the hard palate usually requires excision of underlying bone producing an opening into the antrum. This defect can be filled and covered with a dental prosthesis, a maneuver that restores satisfactory swallowing and speech.

Patients who smoke while on radiation therapy appear to have lower response rates and shorter survival durations than those who do not; [8] therefore, patients should be counseled to stop smoking before beginning radiation therapy. Dental status evaluation should be performed prior to therapy to prevent late sequelae.

References:

1.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2.         Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.

3.         Myers EN, Suen JY, eds.: Cancer of the Head and Neck. 3rd ed. Philadelphia, Pa: Saunders, 1996.

4.         Freund HR: Principles of Head and Neck Surgery. 2nd ed. New York, NY: Appleton-Century-Crofts, 1979.

5.         Lore JM: An Atlas of Head and Neck Surgery. 3rd ed. Philadelphia, Pa: Saunders, 1988.

6.         Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992.

7.         Langendijk JA, de Jong MA, Leemans ChR, et al.: Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time. Int J Radiat Oncol Biol Phys 57 (3): 693-700, 2003.

8.         Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993.

Stage I Lip and Oral Cavity Cancer

Surgery and/or radiation therapy may be used, depending on the exact site. [1] [2]

Small Lesions of the Lip

Standard treatment options:

•           Surgery and radiation therapy produce similar cure rates, and the method of treatment is dictated by the anticipated cosmetic and functional results.

Small Anterior Tongue Lesions

Standard treatment options:

1.         Wide local excision is often used for small lesions that can be resected transorally.

2.         For larger T1 lesions, either surgery or radiation therapy is an acceptable treatment. Interstitial implantation alone or with external-beam radiation therapy should be considered. Consideration should be given to irradiating the neck.

Small Lesions of the Buccal Mucosa

Standard treatment options:

1.         Lesions smaller than 1 cm in diameter may be managed by surgery alone if the commissure is not involved. If the commissure is involved, radiation therapy (including brachytherapy) should be considered.

2.         Larger T1 lesions may be treated by surgical excision with split-thickness skin graft or radiation therapy.

Small Lesions of the Floor of the Mouth

Standard treatment options:

1.         Surgery and radiation therapy produce similar cure rates for T1 lesions.

2.         In general for lesions smaller than 0.5 cm, excision alone is adequate if there is a margin of normal mucosa between the lesion and the gingiva.

3.         For larger lesions, surgery is often used if the lesion is attached to the periosteum, whereas radiation therapy is often used if the lesion encroaches on the tongue.

Small Lesions of the Lower Gingiva

Standard treatment options:

1.         Small lesions may be treated by intraoral resection with or without a rim resection of bone and repaired with a split-thickness skin graft.

2.         Radiation therapy may be used for small lesions but results are generally better after surgery alone.

Small Tumors of the Retromolar Trigone

Standard treatment options:

1.         For early lesions without detectable bone invasion, limited resection of the mandible is performed.

2.         If limited resection is not feasible, radiation therapy may be used initially with surgery reserved for radiation failure.

Small Lesions of the Upper Gingiva and Hard Palate

Standard treatment options:

1.         Most small lesions are treated by surgical resection.

2.         Postoperative radiation therapy may be used if appropriate.

References:

1.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2.         Guerry TL, Silverman S Jr, Dedo HH: Carbon dioxide laser resection of superficial oral carcinoma: indications, technique, and results. Ann Otol Rhinol Laryngol 95 (6 Pt 1): 547-55, 1986 Nov-Dec.

Stage II Lip and Oral Cavity Cancer

Surgery and/or radiation therapy may be used, depending on the exact site. [1]

Small Lesions of the Lip

Standard treatment options:

1.         Surgery is used for smaller T2 lesions on the lower lip if simple closure produces an acceptable cosmetic result.

2.         If a reconstructive surgical procedure is required, radiation therapy has the advantage of producing a relatively better functional and cosmetic result with intact skin and muscle innervation.

3.         Radiation therapy may include external-beam and/or interstitial techniques as appropriate.

Small Anterior Tongue Lesions

Standard treatment options:

1.         Radiation therapy is usually selected for T2 lesions that have minimal infiltration to preserve speech and swallowing. Surgery is reserved for patients for whom radiation treatment failed. Neck dissection may be considered when primary brachytherapy is used. [2]

2.         Deeply infiltrative lesions are best treated by surgery, radiation therapy, or a combination of both.

Small Lesions of the Buccal Mucosa

Standard treatment options:

1.         Small T2 lesions (≤3 cm) are usually treated by radiation therapy.

2.         Large T2 lesions (>3 cm) may be treated by surgery, radiation therapy, or a combination of these, if indicated. Radiation therapy is often used if the lesion involves the commissure. Surgery is often used if tumor invades the mandible or maxilla.

Small Lesions of the Floor of the Mouth

Standard treatment options:

1.         For small T2 lesions (≤3 cm), surgery is often used if the lesion is attached to the periosteum, whereas radiation therapy is often used if the lesion encroaches on the tongue.

2.         For large T2 lesions (>3 cm), surgery and radiation therapy are alternative methods of treatment, the choice of which depends primarily on the expected extent of disability from surgery.

3.         External-beam radiation therapy with or without interstitial radiation therapy should be considered postoperatively for larger lesions.

Small Lesions of the Lower Gingiva

Standard treatment options:

1.         Small lesions may be treated by intraoral resection with or without a rim resection of bone and repaired with a split-thickness skin graft.

2.         Radiation therapy may be used for small lesions, but results are generally better after surgery alone.

Small Tumors of the Retromolar Trigone

Standard treatment options:

1.         For early lesions without detectable bone invasion, limited resection of the mandible is performed.

2.         If limited resection is not feasible, radiation therapy may be used initially with surgery reserved for radiation failure.

Small Lesions of the Upper Gingiva and Hard Palate

Standard treatment options:

•           Most lesions are treated by surgical resection with postoperative radiation therapy as appropriate. A small study showed that radiation therapy may be used effectively as the sole treatment modality. [3]

References:

1.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2.         Pernot M, Malissard L, Aletti P, et al.: Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques. Radiother Oncol 23 (4): 223-8, 1992.

3.         Yorozu A, Sykes AJ, Slevin NJ: Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases. Oral Oncol 37 (6): 493-7, 2001.

Stage III Lip and Oral Cavity Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Surgery and/or radiation therapy are used, depending on the exact tumor site. [1] [2] Neoadjuvant chemotherapy, as given in clinical trials, has been used to shrink tumors and thereby render them more definitively treatable with either surgery or radiation. Neoadjuvant chemotherapy is given prior to the other modalities, as opposed to standard adjuvant chemotherapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used as neoadjuvant chemotherapy. [3] [4] [5] [6] Randomized prospective trials, however, have yet to demonstrate a benefit in either disease-free or overall survival for patients receiving neoadjuvant chemotherapy. [7]

Advanced Lesions of the Lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy. Such patients are appropriate candidates for clinical trials.

Standard treatment options:

1.         Surgery: A variety of surgical approaches can be used depending on the size and location of the lesion and the needs for reconstruction.

2.         Radiation therapy: A variety of radiation therapy techniques can be used as dictated by the size and location of the lesion. Options include external-beam radiation therapy (EBRT) with or without brachytherapy.

Treatment options under clinical evaluation:

1.         Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate. [3] [4] [5] [6] [8] [9] [10] Information about ongoing clinical trials is available from the NCI Web site.

2.         Superfractionated radiation therapy. [11]

Moderately Advanced (Late T2, Small T3) Lesions of the AnteriorTongue

Standard treatment options:

1.         Minimally infiltrative lesions may be treated with external-beam radiation therapy with or without interstitial implant.

2.         Deeply infiltrative lesions may be treated with surgery with postoperative radiation therapy. [2]

Advanced Lesions of the Buccal Mucosa

Standard treatment options:

1.         Radical surgical resection alone.

2.         Radiation therapy alone.

3.         Surgical resection plus radiation therapy, generally postoperative.

Treatment options under clinical evaluation:

•           Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate. [3] [4] [5] [6] [8] [9] [10] [12] Information about ongoing clinical trials is available from the NCI Web site.

Moderately Advanced Lesions of the Floor of the Mouth

Standard treatment options:

1.         Surgery: Rim resection plus neck dissection or partial mandibulectomy with neck dissection as appropriate.

2.         Radiation therapy: EBRT alone or EBRT plus an interstitial implant.

Treatment options under clinical evaluation:

1.         Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate. [3] [4] [5] [6] [8] [9] [10] [12] Information about ongoing clinical trials is available from the NCI Web site.

2.         Clinical trials using novel radiation therapy fractionation schemas. [13]

Moderately Advanced Lesions of the Lower Gingiva

Standard treatment options:

•           Extensive lesions with moderate bone destruction and/or nodal metastases should be treated by combined radiation therapy and radical resection or by radical resection alone. Radiation therapy may be either preoperative or postoperative.

Advanced Lesions of the Retromolar Trigone

Standard treatment options:

•           Surgical composite resection that may be followed by postoperative radiation therapy.

Treatment options under clinical evaluation:

1.         Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, as adjuvant therapy after surgery, or as part of combined modality therapy are appropriate. [3] [4] [5] [6] [8] [9] [10] [12] Information about ongoing clinical trials is available from the NCI Web site.

2.         Clinical trials using novel radiation therapy fractionation schemas. [13]

Moderately Advanced Lesions of the Upper Gingiva

Standard treatment options:

1.         Superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate may be treated by radiation therapy alone.

2.         Deeply invasive lesions involving bone should be treated by a combination of surgery and radiation therapy.

Moderately Advanced Lesions of the Hard Palate

Standard treatment options:

1.         Superficial lesions with extensive involvement of the gingiva, hard palate, or soft palate may be treated by radiation therapy alone.

2.         Deeply invasive lesions involving bone should be treated by a combination of surgery and radiation therapy or by surgery alone.

Treatment options for management of lymph nodes: [1]

•           Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread to involve the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle ( i.e., orbicularis oris).

Standard treatment options:

1.         Radiation therapy alone or neck dissection:

o          N1 (0–2 cm).

o          N2b or N3; all nodes smaller than 2 cm. (A combined surgical and radiation therapy approach should also be considered.)

2.         Radiation therapy and neck dissection:

o          N1 (2–3 cm), N2a, N3.

3.         Surgery followed by radiation therapy, indications for which are as follows:

o          Multiple positive nodes.

o          Contralateral subclinical metastases.

o          Invasion of tumor through the capsule of the lymph node.

o          N2b or N3 (one or more nodes in each neck, as appropriate, >2 cm).

4.         Radiation therapy prior to surgery:

o          Large fixed nodes.

Treatment options under clinical evaluation (all stage III lesions):

•           Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable. [8] [10] [14] [15]

A meta-analysis of 63 randomized prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy. [16][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data were not available; no standard regimen existed; and the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oral cavity cancer.

The best chemotherapy to use and the appropriate way to integrate the two modalities is still unresolved. [17]

Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

Novel fractionation radiation therapy clinical trials are under clinical evaluation. [13] Information about ongoing clinical trials is available from the NCI Web site.

References:

1.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

2.         Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.

3.         Ervin TJ, Clark JR, Weichselbaum RR, et al.: An analysis of induction and adjuvant chemotherapy in the multidisciplinary treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol 5 (1): 10-20, 1987.

4.         Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987.

5.         Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. Cancer 60 (3): 301-11, 1987.

6.         Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57 (4): 711-7, 1986.

7.         Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.

8.         Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.

9.         Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.

10.       Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.

11.       Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.

12.       Licitra L, Grandi C, Guzzo M, et al.: Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 21 (2): 327-33, 2003.

13.       Stuschke M, Thames HD: Hyperfractionated radiotherapy of human tumors: overview of the randomized clinical trials. Int J Radiat Oncol Biol Phys 37 (2): 259-67, 1997.

14.       Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.

15.       Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.

16.       Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.

17.       Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.

Stage IV Lip and Oral Cavity Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Randomized, prospective trials have yet to demonstrate a benefit in either disease-free or overall survival for patients receiving neoadjuvant chemotherapy. [1] The use of isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primaries is under clinical evaluation. [2]

Advanced Lesions of the Lip

These lesions, including those involving bone, nerves, and lymph nodes, generally require a combination of surgery and radiation therapy. Such patients are appropriate candidates for clinical trials.

Standard treatment options:

1.         Surgery: A variety of surgical approaches can be used depending on the size and location of the lesion and the need for reconstruction. Treatment of both sides of the neck is indicated for selected patients.

2.         Radiation therapy: A variety of radiation therapy techniques can be used as dictated by the size and location of the lesion. Options include external-beam radiation therapy with or without brachytherapy.

Treatment options under clinical evaluation:

•           Superfractionated radiation therapy. [3]

Advanced Lesions of the Anterior Tongue

Standard treatment options:

1.         Selected patients may be treated with combined surgery (i.e., total glossectomy, sometimes requiring laryngectomy) that may be combined with postoperative radiation therapy. [4]

2.         Patients with very-advanced lesions may be treated with palliative radiation therapy.

Advanced Lesions of the Buccal Mucosa

Standard treatment options:

1.         Radical surgical resection alone.

2.         Radiation therapy alone.

3.         Surgical resection plus radiation therapy, generally postoperative.

Advanced Lesions of the Floor of the Mouth

Standard treatment options:

1.         A combination of surgery and radiation therapy, generally postoperative, is often used.

2.         For fixed nodes (≥5 cm) preoperative radiation therapy is often used.

Advanced Lesions of the Lower Gingiva

Standard treatment options:

•           Far-advanced tumors with extensive destruction of the mandible and with nodal metastases are poorly controlled by surgery, radiation therapy, or a combination of both.

Advanced Lesions of the Retromolar Trigone

Standard treatment options:

•           Surgical composite resection followed by postoperative radiation therapy.

Advanced Lesions of the Upper Gingiva

Standard treatment options:

•           Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.

Advanced Lesions of the Hard Palate

Standard treatment options:

•           Lesions that are extensive and infiltrating generally require treatment by surgery in combination with radiation therapy.

Treatment options for management of lymph nodes: [5]

Patients with advanced lesions should have elective lymph node radiation therapy or node dissection. The risk of metastases to lymph nodes is increased by high-grade histology, large lesions, spread involving the wet mucosa of the lip or the buccal mucosa in patients with recurrent disease, and invasion of muscle (orbicularis oris).

Standard treatment options:

1.         Radiation therapy alone or neck dissection:

o          N1 (0–2 cm).

o          N2b or N3; all nodes smaller than 2 cm. (A combined surgical and radiation therapy approach should also be considered.)

2.         Radiation therapy and neck dissection:

o          N1 (2–3 cm), N2a, N3.

3.         Surgery followed by radiation therapy is indicated for the following:

o          Multiple positive nodes.

o          Contralateral subclinical metastases.

o          Invasion of tumor through the capsule of the lymph node.

o          N2b or N3 (one or more nodes in each neck, as appropriate, >2 cm).

4.         Radiation therapy prior to surgery:

o          Large fixed nodes.

Treatment options under clinical evaluation (all stage IV lesions):

1.         Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable. [6] [7] [8] [9]

A meta-analysis of 63 randomized prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy. [10][Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data were not available; no standard regimen existed; and the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oral cavity cancer.

The best chemotherapy to use and the appropriate way to integrate the two modalities is still unresolved. [11]

Similar approaches in the patient with resectable disease, in whom resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

2.         Clinical trials for advanced tumors evaluating the use of chemotherapy preoperatively, before radiation therapy, or as adjuvant therapy after surgery are appropriate. [6] [12] [13] [14] [15] [16] [17] [18] [19] Information about ongoing clinical trials is available from the NCI Web site.

3.         Novel fractionation radiation therapy clinical trials are under clinical evaluation. [20]

References:

1.         Mazeron JJ, Martin M, Brun B, et al.: Induction chemotherapy in head and neck cancer: results of a phase III trial. Head Neck 14 (2): 85-91, 1992 Mar-Apr.

2.         Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.

3.         Johnson CR, Khandelwal SR, Schmidt-Ullrich RK, et al.: The influence of quantitative tumor volume measurements on local control in advanced head and neck cancer using concomitant boost accelerated superfractionated irradiation. Int J Radiat Oncol Biol Phys 32 (3): 635-41, 1995.

4.         Franceschi D, Gupta R, Spiro RH, et al.: Improved survival in the treatment of squamous carcinoma of the oral tongue. Am J Surg 166 (4): 360-5, 1993.

5.         Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.

6.         Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.

7.         Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.

8.         Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.

9.         Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.

10.       Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.

11.       Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.

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The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering and save lives through prevention, education, research, advocacy, and support activities. Oral cancer is the largest group of those cancers which fall into the head and neck cancer category. Common names for it include such things as mouth cancer, tongue cancer, and throat cancer. Approximately 34,000 people in the US will be newly diagnosed with oral cancer in 2007. This is the second year in a row in which there has been an increase in the rate of occurrence, this time of about 11% over last year. There are two distinct pathways by which most people come to oral cancer. One is through the use of tobacco and alcohol, and the other is through exposure to the HPV-16 virus (human papilloma virus), the same one which is responsible for the vast majority of cervical cancers in women.

Worldwide the problem is far greater, with new cases annually exceeding 481,000. In the US alone, a person dies from oral cancer every hour of every day. If you add the sub category of laryngeal cancers, the rates of occurrence (about 10,000 additional new cases per year) and death are significantly higher. When found early, oral cancers have an 80 to 90 % survival rate. Unfortunately at this time, the majority are found as late stage cancers, and this accounts for the very high death rate of about 50% at five years from diagnosis. This site will provide you with hundreds of pages of information about the rates of occurrence, risk factors which lead to oral cancer, sign and symptoms, treatments, current research, and current oral cancer related news.

A patient / survivor forum is open to the public where those currently fighting oral cancer can gain insights and inspiration from those who have been there before them. A comprehensive resource list is available to link you to other pertinent oral cancer data on the web and elsewhere for patients, caregivers, and the public.

The oral cavity includes the following:

• The front two thirds of the tongue.

• The gingiva (gums).

• The buccal mucosa (the lining of the inside of the cheeks).

• The floor (bottom) of the mouth under the tongue.

• The hard palate (the roof of the mouth).

• The retromolar trigone (the small area behind the wisdom teeth).

Most lip and oral cavity cancers start in squamous cells, the thin, flat cells that line the lips and oral cavity. These are called squamous cell carcinomas. Cancer cells may spread into deeper tissue as the cancer grows. Squamous cell carcinoma usually develops in areas of leukoplakia (white patches of cells that do not rub off).

Tobacco and alcohol use can affect the risk of developing lip and oral cavity cancer.

Risk factors for lip and oral cavity cancer include the following:

• Using tobacco products.

• Heavy alcohol use.

• Being exposed to sunlight.

• Being male.

• Being infected with human papillomavirus (HPV).

Possible signs of lip and oral cavity cancer include a sore or lump on the lips or in the mouth.

These and other symptoms may be caused by lip and oral cavity cancer. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

• A sore on the lip or in the mouth that does not heal.

• A lump or thickening on the lips or gums or in the mouth.

• A white or red patch on the gums, tongue, tonsils, or lining of the mouth.

• Bleeding, pain, or numbness in the lip or mouth.

• Change in voice.

• Loose teeth or dentures that no longer fit well.

• Trouble chewing or swallowing or moving the tongue or jaw.

• Swelling of jaw.

• Sore throat or feeling that something is caught in the throat.

Lip and oral cavity cancer may not have any symptoms and is sometimes found during a regular dental exam.

Tests that examine the mouth and throat are used to detect (find), diagnose, and stage lip and oral cavity cancer.

The following tests and procedures may be used:

Physical exam of the lips and oral cavity: An exam to check the lips and oral cavity for abnormal areas. The doctor or dentist will feel the entire inside of the mouth with a gloved finger and examine the oral cavity with a small long-handled mirror and lights. This will include checking the insides of the cheeks and lips; the gums; the roof and floor of the mouth; and the top, bottom, and sides of the tongue. The neck will be felt for swollen lymph nodes. A history of the patient’s health habits and past illnesses and medical and dental treatments will also be taken.

Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope (a thin, lighted tube) is inserted through an incision (cut) in the skin or opening in the body, such as the mouth. Tissue samples and lymph nodes may be taken for biopsy.

X-rays of the head, neck, and chest: An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist. If leukoplakia is found, cells taken from the patches are also checked under the microscope for signs of cancer.

MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

Exfoliative cytology: A procedure to collect cells from the lip or oral cavity. A piece of cotton, a brush, or a small wooden stick is used to gently scrape cells from the lips, tongue, mouth, or throat. The cells are viewed under a microscope to find out if they are abnormal.

Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metallic compound). The liquid coats the esophagus and x-rays are taken. This procedure is also called an upper GI series.

PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radionuclide glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

Certain factors affect prognosis (chance of recovery) and treatment options.

Prognosis (chance of recovery) depends on the following:

• The stage of the cancer.

• Where the tumor is in the lip or oral cavity.

• Whether the cancer has spread to blood vessels.

For patients who smoke, the chance of recovery is better if they stop smoking before beginning radiation therapy.

Treatment options depend on the following:

• The stage of the cancer.

• The size of the tumor and where it is in the lip or oral cavity.

• Whether the patient’s appearance and ability to talk and eat can stay the same.

• The patient’s age and general health.

Patients who have had lip and oral cavity cancer have an increased risk of developing a second cancer in the head or neck. Frequent and careful follow-up is important. Clinical trials are studying the use of retinoid drugs to reduce the risk of a second head and neck cancer. Information about ongoing clinical trials is available from the NCI Web site.

Stages of Lip and Oral Cavity Cancer

After lip and oral cavity cancer has been diagnosed, tests are done to find out if cancer cells have spread within the lip and oral cavity or to other parts of the body.

The process used to find out if cancer has spread within the lip and oral cavity or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The results of the tests used to diagnose lip and oral cavity cancer are also used to stage the disease.

The following stages are used for lip and oral cavity cancer:

Stage 0 (Carcinoma in Situ)

In stage 0, cancer is found only in the layer of cells lining the lips and oral cavity. Stage 0 cancer is also called carcinoma in situ.

Stage I

In stage I, the tumor is 2 centimeters or smaller and cancer has not spread to the lymph nodes.

Stage II

In stage II, the tumor is larger than 2 centimeters but not larger than 4 centimeters and cancer has not spread to the lymph nodes.

Stage III

In stage III, the tumor:

• may be any size and has spread to a single lymph node that is 3 centimeters or smaller, on the same side of the neck as the cancer; or

• is larger than 4 centimeters.

Stage IV

Stage IV is divided into stages IVA, IVB, and IVC as follows:

In stage IVA, the tumor:

• has spread to nearby tissues in the lip and oral cavity; or

• is any size and may have spread to nearby tissues in the lip and oral cavity. Cancer has spread to 1 or more lymph nodes on one or both sides of the neck, and the involved lymph nodes are 6 centimeters or smaller.

In stage IVB, the tumor:

• may be any size and has spread to one or more lymph nodes that are larger than 6 centimeters; or

• has spread to the muscles or bones in the oral cavity, or to the base or the skull and/or the carotid artery. Cancer may have spread to one or more lymph nodes on one or both sides of the neck.

In stage IVC, the tumor has spread beyond the lip and oral cavity to other parts of the body. The tumor may be any size and may have spread to the lymph nodes.

Recurrent Lip and Oral Cavity Cancer

Recurrent lip and oral cavity cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the lip or mouth or in other parts of the body.