• The facts about oral cancer (signs, symptoms and factors)

• Physical Risk factors (smoking, drinking, age and HPV)

• Epidemiology and mortality

• Leukoplakia and erythroplakia

• Cancer of the lip

• Tumors of the salivary glands

• Malignant melanoma

• Screening for oral cancer

  • Visual exam

  • Oral CDX

  • Vizilit

Oral Cancer--The facts (and why that lump you noticed in the mirror this morning is probably NOT cancer!)

The five year survival rate for this type of cancer has remained at about 50% since the early 1960's.  About half of the cases occur in persons over the age of 65.

Oral cancer attacks more men than women (male/female ratio = 2/1), and more blacks than whites (black/white ratio  = 2/1).  The survival rate is better for Caucasians (54%) than for Afro-Americans (34%).  The most common sites of oral cancer are the floor of the mouth, the sides and undersurface of the tongue, the back of the throat, and the lips.  Although it is not considered oral cancer in the strict sense, cancer of the larynx (the voice box) has a similar etiology (cause & origin) and causes approximately 2% of all forms of cancer.  90% of the victims of cancer of the larynx are males, and most are between 60 and 70 years old.

Indications that you may have developed oral or laryngial cancer

• A sore in the mouth that does not heal spontaneously within three weeks;
• A lump or thickening in the cheek;
• A white or red patch on the gums, tongue, or lining of the mouth;
• Soreness or a feeling that something is caught in the throat;
• Difficulty chewing or swallowing;
• Difficulty moving the jaw or tongue;
• Numbness of the tongue or other area of the mouth; or
• Swelling of the jaw that causes dentures to fit poorly or become uncomfortable.

  The general characteristics of oral cancer

90% of all oral cancers are of a type called Squamous cell carcinoma, which means that they derive from squamous cells which are the type of cells that make up the pink mucosa that lines the mouth.  Laryngeal cancer (cancer of the vocal cords) is also generally caused by squamous cell carcinoma, and is also associated with heavy smoking.  Most oral cancers tend to happen on the floor of the mouth or the sides and undersurface of the tongue.  They also tend to be relatively painless during their early development.  The image to the right shows a rather advanced cancer on the side of the tongue.  (Click the image to see a larger version, as well as some other rather scary examples of oral cancer.)  Note the mottled white and red appearance of the growth.  As you will see, this is an important characteristic of these cancers. 

It is interesting to note that squamous cell carcinoma is NOT USUALLY one of the more virulent cancers, and yet it kills about half of those that get it.  This is an important point since if it is diagnosed at a reasonably early stage (within the first year, or in some cases within the first two years--The earlier, of course, the better), it can generally be removed before it becomes locally invasive or spreads to other parts of the body and becomes a death dealing issue.  Why would anyone let a problem like this progress until it is this large?  (Click the image for more info on why this one got so big.)  Why does does such a slow growing cancer have such a large mortality rate?  (Mortality rate is the measure of the ratio of those who contract the disease to those who die from it.  In the case of Squamous cell carcinoma, the mortality rate is about 50%, meaning that approximately half the people diagnosed with it will eventually die as a direct result of the cancer, or from complications associated with it.) 

The physical factors that increase the risk of oral cancer

Since 90% of all oral cancers are of a type called Squamous Cell Carcinoma, when we speak of "risk factors" associated with oral cancer, we are talking about risk factors associated with this particular entity.  These risk factors do not pertain to the other 10% of cancers which can occur in the oral cavity.  This 10% are covered later on this page.  There are four factors that appear to increase the risk of developing oral squamous cell carcinoma:

(1)Tobacco AND (2)alcohol--When indulged in together over a long period of time, heavy alcohol and tobacco use are the most potent physical factors contributing to the development of squamous cell carcinoma.  Those who both smoke and drink heavily, have a 15 times greater risk of developing oral cancer than those that have neither habit. 

• Tobacco is a known carcinogen, which means that it is known to damage cellular DNA.  Damaged DNA can cause the cellular reproductive machinery to malfunction, which is the first step in the growth of malignant cellular masses (cancer). 
• Alcohol is known to inhibit a gene that functions in response to DNA damage.  This gene is responsible for initiating cell death in cells in which the the DNA is damaged. 
• Thus the tobacco causes malignant mutations in the cellular DNA, while the alcohol inhibits the body's natural defense against malignancy.

(3)Age--The large majority of squamous cell carcinoma victims are over the age of 45.  This probably relates to the tendency of the immune system to become less and less competent at recognizing and eliminating mutated cells that arise in the body from time to time.  It may also be associated with the time it takes for the other three factors discussed in this section to have their damaging effects.

(4)HPV--The human papilloma virus.  HPV is transferred from person to person by vigorous physical contact, especially oral sexual contact.   The presence of HPV may be the major risk factor in the development of oral cancers in patients who are not heavy smokers and drinkers.  HPV is covered in more detail under the lifestyle discussion below.

Factors relating to epidemiology and mortality in patients with oral and laryngeal cancers (Epidemiology is the study of how a disease spreads and who is likely to get it.)

Lifestyle issues:  

Lifestyle issues are behavior patterns which are considered under the control of the individual.  They are the most important factors in the mortality (death rate) and epidemiology (how the disease spreads, and who is likely to get sick) associated with oral and laryngeal squamous cell cancers.  Patient lifestyle choices probably accounted for the development of the lesions seen in the images on this page, and also contributed to the fact that they grew so large before diagnosis.

• Heavy Drinking-- While alcohol is one of the major physical risk factors in the direct development of oral cancer, heavy drinking (the behavior)  is associated with oral cancer's high mortality (death) rate.  Heavy drinkers are much less likely to notice, let alone seek professional help for a painless growth under their tongues!

• Smoking-- Tobacco has a direct effect on the tissues that the smoke actually comes into contact with.  This includes both the tissues of the mouth, and the tissues in the larynx (voice box).  75% of persons who develop oral squamous cell carcinoma are, or have been heavy smokers.  It appears that the effects of tobacco are cumulative, so people who have been heavy smokers (or snuff dippers) for many years are more at risk for developing oral or laryngeal cancer than those who have only recently started.

• HPV-- When discussing HPV as it relates to oral cancer, the lifestyle issue here relates to sexual behavior.  25% of oral cancers appear in patients who have never smoked, and it is thought that human papilloma virus may be the carcinogenetic element involved in these cases.  There are approximately 80 strains of the human papilloma virus. Many of the strains of HPV cause ordinary warts, the kind that develop on the hands and feet. Most strains of HPV are thought to be harmless, but two types,  HPV16 and 18, have been shown to be the causative agents of cervical cancer (cancer affecting the epithelial cellular layer--the surface cells--surrounding the opening of the uterus) and are spread by sexual means.  These strains of HPV have recently been implicated as a causative agents in oral squamous cell cancer as well.  Since the virus itself is transmitted exclusively by vigorous physical contact, the implication is that oral/genital sexual contact (oral sex) may be the major means of transmission of the virus. 

  • Normal kissing does not seem to be implicated.  Monogamous couples composed of persons who have never engaged in sex outside of their relationship are not at risk either.

  • As the incidence of smoking has declined over the last 30 years in the USA, the incidence of promiscuous sexual contact has risen.  Thus the expected benefit of fewer people smoking has been offset by the liability of more widespread infection with HPV.  This means that the rate of oral cancer diagnosis in the US has remained constant over the last twenty years, instead of falling as might have been the expected with the decline in the number of smokers.

  For more on the human papilloma virus, please see the website of the oral cancer foundation.

Age and its relationship to mortality and epidemiology in oral and laryngeal cancers

One of the most important factors associated with oral cancer is age.  Even in a population of cigarette smoking drinkers, the vast majority who develop oral cancer tend to be over the age of 40.  Half of all oral cancers arise in persons over the age of 65.  Advanced age is probably the most important factor in the mortality associated with the development of any cancer.  This is due to the fact that as a person ages, their immune system tends to become less efficient at recognizing and eliminating aberrant cellular growths which arise from time to time in people of all ages.  Since about half of all cases of oral cancer, and most cases of laryngial cancer occur in patients over the age of 65, the advanced age of the cohort alone would account for a substantial portion of the death rate in these patients.  

 

Painless Lesions contribute to the mortality rate ("Lesions" are abnormal growths, erosions or sores.)

The initial lesions of squamous cell carcinoma tend to be painless.  The fact that they are painless makes them easily overlooked in the early stages.  The lack of pain in early lesions combined with the tendency for this cancer to develop in heavy drinkers may be largely responsible for oral cancer's 50% mortality rate .  These lesions start out as small white or red patches about 1 to 2 mm in diameter and progress toward larger lesions slowly.  They will usually be noted by a patient when they are large enough to be felt during movements of the effected organ.  They generally appear to be irregular sores with a white and red mottled center, surrounded by a red border.  As the lesion enlarges, it may become more and more bound-down to the underlying tissues thus becoming less mobile.  Pain and/or numbness generally develop later in the course of the lesion's growth.

Leukoplakia

Persons who smoke heavily or use smokeless tobacco such as snuff and chewing tobacco tend to get whitish patches called leukoplakia on the oral mucosa (the wet tissue lining the mouth) .  The image on the right shows a fairly typical patch on the side of a man's tongue.  The image to the left shows a similar patch on the floor of the mouth. These patches can happen anywhere in the oral cavity such as on the cheek mucosa, the roof of the mouth, or the back of the throat.  The common denominator seems to be HEAVY use of cigarettes or prolonged contact of snuff or chewing tobacco with cheek tissue.  Leukoplakia is not itself a form of cancer, but is considered pre-cancerous and should be biopsied (a procedure in which a tiny piece of tissue is sent out for microscopic examination) since about 20% are found to be pre-malignant .  It is white, firm tissue and cannot be scraped off.  It generally goes away when the stimulation of the tobacco stops, but with continued heavy tobacco use it can transform into squamous cell cancer.  In order to picture what a cancer developing in these lesions would look like, imagine irregular red blotches developing inside the white leukoplakic plaque, and a large red border developing around the entire lesion!  Erythroplakia (see image at right) is the term applied to red bloches which appear within areas of leukoplakia.  Erythroplakia is considered to be more dangerous than leukoplakia alone.  Click on the image to the left or the one to the imediate right to see these images enlarged, and other scary images of leukoplakia.   Neither leukoplakia nor erythroplakia are contagious conditions.

The number one cancer of the head and neck is cancer of the larynx--the voice box--which is more susceptible to particulate carcinogens such as cigarette smoke and various forms of pollution than other tissues.  The majority of patients who get cancer of the larynx are men between 60 and 70 years old who have a history of heavy smoking and generally heavy drinking.  Women in the same category are also prone to squamous cell carcinoma.

Cancer of the lip

Cancers on the lips are a special case.  They generally strike the lower lip and are more likely to happen after long, repeated episodes of exposure to the sun.  Cancer of the lip is also squamous cell carcinoma and has the same clinical course as intraoral cancers.  Going to the beach several times a summer is generally not a significant risk factor for cancer on the lip.  Most people who get this form of cancer tend to be outdoor workers who labor all day in the sun for years on end.  Perhaps because more people work indoors today than ever before, the incidence of cancer of the lip is decreasing.

What about the other 10% that are not squamous cell carcinoma?

The probability of developing any type of cancer increases with age!  Chronic illness is another factor that increases the likelihood of developing these forms of cancer.  There are, unfortunately, numerous types of cancer that can originate in various oral structures including bone, lymph nodes, salivary glands etc.  These are not associated with known risk factors the way squamous cell cancer is associated with smoking, drinking and promiscuous oral sexual activity. There is some evidence that non squamous cell cancers of the oral cavity are related to precipitating factors such as exposure to the Epstein Barr virus (the virus responsible for mononucleosis which in some persons seems able to remain dormant in the body for a lifetime) as well as the human papillomavirus (HPV), and radiation treatments to the head and neck for cancer or acne (not diagnostic x-rays).  Radiation was once a treatment modality for facial acne (back in the early 20th century) but is no longer used because of the obvious danger from large amounts of radiation. It is still used in the treatment of carcinomas and Sarcomas (two different classifications of malignancy) but is carefully aimed and metered to avoid side effects.  

A minor salivary gland tumor tends to be a firm mass on one side of the palate (the roof of the mouth).  They do not occur in the midline.  If it is cancerous, it will remain enlarged and will not go away after two or three weeks.  About 50% of these large persistent masses will prove to be malignant (cancer).  But be aware that small salivary glands in the palatal mucosa do become infected occasionally.  When this happens, they can become sore and slightly enlarged, but the problem is generally temporary and disappears without treatment within two weeks.

About 80% of all salivary gland tumors  begin in the parotid glands.  (A tumor is simply a mass. It is not necessarily cancerous.)  The patient notes a swelling on the side of the face below and in front of the ear.  This swelling does not get larger and smaller at different times of the day (as salivary gland infections do), but remains constant, or grows larger over time.  10%-15% of salivary gland tumors start in the submandibular glands  causing a swelling on one side of the neck just under the jawline.  These also remain enlarged over time.  The rest develop in the sublingual gland, causing a similar swelling under the chin, or in one of the many minor salivary glands.  Most tumors of the parotids are benign (noncancerous).  Masses in the minor salivary glands (the smallest of salivary glands) are more frequently malignant (cancerous), however because there are so many more parotid gland tumors, a greater number of cancers are found in the parotid glands than any of the other salivary glands.  (For a diagram of the major salivary glands, see my page on Dry Mouth.)

One of the most deadly forms of oral cancer is Malignant melanoma.  Thankfully, it is very rare in the oral cavity.  It begins as small black spot, generally smaller than a millimeter, and develops irregular borders as it grows larger (see image on the right).  Melanoma can happen on any tissue in the mouth, particularly inside the lips, cheeks, undersurface of the tongue and on the hard palate.  It is likely to be tan, dark brown or black, sometimes mixed with red or gray.  

Melanoma occurring anywhere other than the mouth is generally considered to be fairly treatable.  Unfortunately, due to the anatomy of the head and neck, oral melanoma is most often fatal. 

Fortunately, most dark spots on oral tissue are likely to be amalgam tattoos  discussed in more depth on the sores, lumps and bumps page.  Amalgam tattoos happen after dental appointments, remain stable, do not grow larger over time, and are relatively circumscribed (without diffuse, irregular borders).  They also tend to have a blue-gray color, unlike the dark brown or black seen in melanoma. They are most common on the gums, cheeks and floor of mouth immediately adjacent to teeth.  Amalgam tattoos attain and maintain their maximum size shortly after the introduction of the amalgam into the tissue, while melanomas will grow and change shape over the course of a week or two.

How dentists screen for oral cancer

Although screening by your dentist is the best method of reducing the pain, suffering and mortality related to oral cancers, it is not altogether reassuring to know that differentiating early malignant and premalignant lesions from benign growths is quite difficult, even for experienced dental practitioners.  Early stage oral cancers are asymptomatic and the clinical characteristics associated with malignancy such as pain, swelling, redness, enlargement, fixation (becoming bound down to underlying tissue) and deformation of the surrounding tissues generally do not develop until quite late in the clinical course of the disease.  

Until recently, there were only two courses a dentist could take when he saw a suspicious early lesion.  ("Lesions" are abnormal growths, erosions or sores.)  The first, and most frequent course was waiting several weeks to see if the lesion progressed or regressed.  If It went away, all was well, and the crisis was averted.  If it got bigger, or if the lesion had been present for several weeks and was already of significant size on initial examination, then the dentist proceeded to the second course which is a sectional (knife) biopsy in which the patient is anesthetized and a piece of the lesion is surgically removed and sent to a laboratory in formalin for microscopic analysis.  The microscopic examination of the tissue sample provides a definitive diagnosis upon which to base a treatment plan.  

The difficulty with this protocol is that there is a high incidence of oral abnormalities which can be candidates for biopsy.  It is claimed that between 5 and 15% of all new patients present with abnormal lesions in their mouths, however these include such lesions as aphthous, fibromas and many of the other obviously benign conditions explained on this page.  No knowledgeable dentist would consider these to be candidates for biopsy.  Even so, quite a few truly suspicious lesions do walk through our doors with only about 5% turning out to be cancer.  Given these odds, it is impractical to immediately subject all these lesions to a potentially painful procedure like a surgical biopsy.  Thus, using the older protocol, virtually everyone presenting with an early lesion was sent home to wait the obligatory two to three weeks to see if it progressed or not.  While not a dangerous course of action, it still left any potential malignancy to progress for the entire waiting period plus whatever time it took to examine the biopsy tissue.  It was not especially reassuring for either the dentist or the patient to know that if there was a cancerous lesion, it had to wait at least a month to be removed!

A better screening method has recently become available.  It is called the Brush Biopsy (Oral CDx).  This consists of placing a small, sterile, hard bristled brush over the lesion and twirling it around until part of surface of the lesion is abraded away.  The procedure rakes up cellular material from the entire thickness of the surface of the lesion onto the brush.  Although this procedure may irritate the area, (it should produce pinpoint bleeding areas) it does not generally require local anesthesia.  The cellular material scraped up on the brush is smeared onto a glass slide, fixed with a chemical that comes with the kit, and dried.  The glass slide is then placed into a plastic container and sent to a lab for computer scanning and further manual examination of suspicious cells.  The makers of this biopsy kit claim 100% accuracy in identification of abnormal cellular components provided that the clinician was aggressive enough in obtaining a full thickness sample.  The brush biopsy does NOT establish a definitive diagnosis.  It does indicate the need for a surgical biopsy to establish the diagnosis. The brush biopsy is not suitable for melanoma ( pigmented lesions) or lesions on the dry parts of the lips.  It is generally reserved for use on lesions that show eroded or overgrown mucosal surfaces.  Its principle use is for pre-cancerous lesions that will develop into squamous cell carcinoma.  It is not useful for deeper lesions such salivary gland tumors. Vizilite Zila Pharmaceuticals has heavily marketed a light source which, when shined on oral mucosa is reputed to cause squamous cell carcinoma lesions to fluoresce, thus helping a trained clinician to spot them for early detection of oral cancer.  This product is called Vizilite, and it is heavily marketed to dentists.  It would be a great benefit for the early detection of oral cancer if......it actually worked as advertised. In 2004, "the manufacturers of Vizilite applied to the ADA for the ADA Seal of Acceptance for their product. The official seal of acceptance is considered the ultimate in product recognition in terms of marketing a given product for use in dentistry in the United States. The Council on Scientific Affairs is charged with the review of all studies related to products requesting the seal.  The companies are asked to submit all studies that support their claims. They are required to submit at least two credible clinical studies. The usual requirement is that of two independent double blind clinical trials, each conducted at a separate site.  In addition to the review of this data by the entire Council on Scientific Affairs, the studies are sent out to a number of outside reviewers.  The conclusion on Vizilite was quite clear.  Their submitted study data was extremely weak.  All outside consultants were in agreement in not supporting the product for the seal.  The Council was unanimous in not supporting the application."  (Click here for the reference) This light source has apparently been shown to be beneficial in the differentiation of cervical (uterine) squamous cell carcinoma.   It appears, however, that the progression of the same cancer in the oral cavity is biologically different from the progression of cervical squamous cell carcinoma, and for this reason, it is of limited use in the oral cavity.  Therefore, the use of the Vizilite as a method of screening for oral cancer is probably more of an unnecessary expense than a benefit to either patients or the doctors using it. Even so, the manufacturers of Vizilite continue to heavily market the product, and even advertise in the Journal of the American Dental Association.  The presence of an ad in the Journal does not mean that the ADA endorses the product, any more than an ad on this website means that I endorse the product.

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