Demographics

As one would expect, squamous cell carcinoma behaves like most other carcinomas in that it becomes more prevalent with increased age. To fully understand the published statistics in the literature, the reader must first determine which reference points are being used. In some literature the statistics are based solely on intraoral disease and do not include any disease of the vermillion region. The contrary is apparent in many other articles, where all areas of the mouth are included in the definition. Neville and colleagues conclude that in the United States the incidence of intraoral cancer is highest in white males older than 65 years. For middle-aged males the highest incidence occurs in African American males. According to all sources, the rate of oral cancer continues to increase in the African American community; by contrast the rates are decreasing for non-blacks. A good reference for the epidemiology of the disease is the United States Government Surveillance Epidemiology and End Results Report (SEER). Females of all ethnicities and races in the United States have a lower incidence of the disease according to the National Cancer Institute. However, within this group African American females have the highest incidence and mortality rates, just like their male counterparts.

We now live in a global society so we should be somewhat familiar with global statistics. Whites and blacks are still more likely to suffer the effects of this disease and, consistent with what is found in the United States, males more so than females. One very interesting fact put forward by the National Cancer Institute is that Filipinos are the only race in whom the incidence of oral cancer is the same for both males and females.

Etiology

Most literature concedes that oral cancer has a high correlation with a person’s lifestyle. There are multiple extrinsic agents associated with oral cancer. Tobacco use of all types, whether it be pipes, cigars, cigarettes, or smokeless tobacco, must also be included as one of the major causes. Betel nut chewing, practiced in parts of Asia, also has a high association. Over a lifetime people who chew these nuts, which come from the areca palm, have an 8% chance of contracting oral cancer. The next major association is alcohol consumption and abuse. It is not widely thought that alcohol by itself is a major inducing agent. However, in conjunction with tobacco use it is thought to have a potentiating effect. According to Kuriakose and Sharan, the risk for development of oral cancer is 3 to 9 times greater in people who drink or smoke and up to 100 times greater in people who drink and smoke heavily.

Iron deficiency is also associated with an increased risk of squamous cell carcinoma of the esophagus, oropharynx, and posterior mouth. Patients with Plummer-Vinson and Paterson-Kelly syndromes are at highest risk. Vitamin A deficiency has also been shown to place individuals at risk for oral cancer. Research has shown that people whose diets are lacking fruits and vegetables are more susceptible to the disease. Blood levels of retinol and the amounts of dietary β-carotene ingested are inversely proportional to the risk of contracting oral squamous cell carcinoma and leukoplakia.

A thorough knowledge of the causative agents of cancer will help in the prevention and early detection of the disease. Because most people contract the disease after age of 40, some of the literature places age as a risk factor. “The age of diagnosed patients may indicate a time component in the biochemical or biophysical processes of aging cells that allows malignant transformation, or perhaps, immune system competence diminishes with age.”

New research has shown that there are biologic risk factors as well. Tumor-producing viruses are thought to play a role in the development of oral squamous carcinoma. Human papillomavirus 16 (HPV 16) has been definitively implicated in oral cancers, particularly those that occur in the posterior oral cavity and oropharynx. HPV 16 and HPV 18 are the primary biologic agents associated with cervical cancer. These cancer-associated types of HPV cause dysplastic tissue growths that usually appear flat and are nearly invisible. Dysplastic tissue is the presence of abnormal cells on the surface of the skin. Dysplasia is not cancer, but is a tissue change often seen prior to invasive malignancy. These biologic factors are not thought to follow the same mechanism as the extrinsic factors. HPV-related disease appears to occur on the tonsillar area, the base of the tongue, and the oropharynx, and non-HPV–positive tumors tend to involve the anterior tongue, floor of the mouth, the mucosa that covers the inside of the cheeks, and alveolar ridges. At the cellular level, the mouth is structurally very similar to the vagina and cervix. These organs have the same type of epithelial cells that are the targeted by HPV. The majority of oral cancers are of epithelial cells, primarily squamous cell carcinomas, not unlike the cancers that affect the cervix. It has been shown that smoking and drinking alcohol help promote HPV invasion, especially marijuana smoking.

HPV 16 tumors usually occur in a younger population than the tobacco and alcohol malignancies. Tobacco oral cancers occur most frequently in the fifth through the seventh decade of life, more so in white males and in nonsmokers. “The HPV positive group is the fastest growing segment of the oral cancer population.”

Etiology

Most literature concedes that oral cancer has a high correlation with a person’s lifestyle. There are multiple extrinsic agents associated with oral cancer. Tobacco use of all types, whether it be pipes, cigars, cigarettes, or smokeless tobacco, must also be included as one of the major causes. Betel nut chewing, practiced in parts of Asia, also has a high association. Over a lifetime people who chew these nuts, which come from the areca palm, have an 8% chance of contracting oral cancer. The next major association is alcohol consumption and abuse. It is not widely thought that alcohol by itself is a major inducing agent. However, in conjunction with tobacco use it is thought to have a potentiating effect. According to Kuriakose and Sharan, the risk for development of oral cancer is 3 to 9 times greater in people who drink or smoke and up to 100 times greater in people who drink and smoke heavily.

Iron deficiency is also associated with an increased risk of squamous cell carcinoma of the esophagus, oropharynx, and posterior mouth. Patients with Plummer-Vinson and Paterson-Kelly syndromes are at highest risk. Vitamin A deficiency has also been shown to place individuals at risk for oral cancer. Research has shown that people whose diets are lacking fruits and vegetables are more susceptible to the disease. Blood levels of retinol and the amounts of dietary β-carotene ingested are inversely proportional to the risk of contracting oral squamous cell carcinoma and leukoplakia.

A thorough knowledge of the causative agents of cancer will help in the prevention and early detection of the disease. Because most people contract the disease after age of 40, some of the literature places age as a risk factor. “The age of diagnosed patients may indicate a time component in the biochemical or biophysical processes of aging cells that allows malignant transformation, or perhaps, immune system competence diminishes with age.”

New research has shown that there are biologic risk factors as well. Tumor-producing viruses are thought to play a role in the development of oral squamous carcinoma. Human papillomavirus 16 (HPV 16) has been definitively implicated in oral cancers, particularly those that occur in the posterior oral cavity and oropharynx. HPV 16 and HPV 18 are the primary biologic agents associated with cervical cancer. These cancer-associated types of HPV cause dysplastic tissue growths that usually appear flat and are nearly invisible. Dysplastic tissue is the presence of abnormal cells on the surface of the skin. Dysplasia is not cancer, but is a tissue change often seen prior to invasive malignancy. These biologic factors are not thought to follow the same mechanism as the extrinsic factors. HPV-related disease appears to occur on the tonsillar area, the base of the tongue, and the oropharynx, and non-HPV–positive tumors tend to involve the anterior tongue, floor of the mouth, the mucosa that covers the inside of the cheeks, and alveolar ridges. At the cellular level, the mouth is structurally very similar to the vagina and cervix. These organs have the same type of epithelial cells that are the targeted by HPV. The majority of oral cancers are of epithelial cells, primarily squamous cell carcinomas, not unlike the cancers that affect the cervix. It has been shown that smoking and drinking alcohol help promote HPV invasion, especially marijuana smoking.

HPV 16 tumors usually occur in a younger population than the tobacco and alcohol malignancies. Tobacco oral cancers occur most frequently in the fifth through the seventh decade of life, more so in white males and in nonsmokers. “The HPV positive group is the fastest growing segment of the oral cancer population.”

Prevention

The obvious method of preventing oral cancer would be to refrain from alcohol and tobacco use; however, it is not quite that simple. In a 2005 article in JADA , Cruz and colleagues split prevention into two categories. Primary prevention, as they called it, consists of “avoidance of tobacco use and alcohol abuse, as well as appropriate intake of fruits and vegetables.” Secondary prevention consists of regular oral head and neck examinations, and treatment of any premalignant conditions or in situ neoplasms.

In 2000 the Department of Health and Human Services published a report called Healthy People 2000 , which consisted of several goals and guidelines to not only prevent but also to reduce oral cancer Box 1 .

As the goals were published back in 2000, they fail to address one of the major concerns of today, namely the transmission of the HPV virus. The transmission of HPV to the oral cavity through unprotected oral sex is becoming very prevalent.

It would seem, therefore, that education and health care promotion may hold the key to reducing the number of cases of oral cancer. With regard to cigarette smoking, great strides have been made in reducing the number of smokers in the United States. A similar government initiative will be required if the amount of alcohol consumed in this country is to be reduced. Regarding education, both physicians and dentists must also play their part. It is imperative that both disciplines stay up to date with the latest knowledge and technology pertinent to this matter. For physicians it is also imperative that if they are in any doubt they refer suspicious oral lesions to the dentists. All patients should undergo head and neck examinations yearly or every 6 months if they exhibit risk factors associated with the disease. Patients from lower socioeconomic brackets are more likely to visit a medical doctor than a dentist when they have symptoms that do not involve the teeth.

It is essential that health care providers understand the oral cancer examination procedure, and know the clinical appearance of oral precancerous and cancerous lesions, thus allowing them to routinely perform a systematic oral cancer examination for all their patients.

There have been no studies conducted in the United States to determine the impact of head and neck examinations and the early detection of cancer. Sensitivity and specificity tests have reported rates ranging from 58% to 99%. Many investigators have suggested that sensitivity will be improved when providers are better trained to recognize specific signs and symptoms of early cancer and pre-cancer. Furthermore, they suggest that if practitioners understand disease progression and regression, they will be more likely to detect disease in its early stages.

Sensitivity is the proportion of truly diseased persons in the screened population who are identified as diseased by the screening test, that is, the probability of correctly diagnosing a case, or the true positive rate. Specificity is the proportion of truly nondiseased persons who are so identified by the screening test, that is, the probability of correctly identifying a nondiseased person with a screening test, or the true negative rate. (Definition from JM Last’s A Dictionary of Epidemiology , Oxford Press, 1988.)

Chemoprevention

Chemoprevention is defined as the administration of agent(s) to block or reverse carcinogenesis. With regard to oral cancer, the goal of chemoprevention has been to reverse any premalignant transformations and the prevention of second primary tumors. The agents associated with chemoprevention of oral cancer are retinoids, β-carotene, vitamin E, selenium, and cyclooxygenase-2 inhibitors. In 2003 the National Cancer Institute reported a negative result for the use of ketorolac in topical form for oral leukoplakia.

β-Carotene and the retinoids are the most commonly used antioxidant supplements for chemoprevention of oral cancer. The success rate of these agents is unreliable at best, but they still may be appropriate if there is recurrence after surgical excision. Patients with leukoplakia involving a large area of the oral mucosa might also be candidates for antioxidants, as might patients with extensive medical problems that increase their surgical risk.

Retinoids are compounds consisting of natural forms or synthetic analogues, and are the most widely investigated agents for chemoprevention in oral cancer. Of the more than 1500 synthetic analogues of vitamin A, 13- cis -retinoic acid (13-cRA), also known as isotretinoin or Accutane, has generated the most interest. 13-cRA has been shown to cause temporary remission of oral leukoplakia, but it also causes side effects in a high percentage of patients. A study done by Hong and colleagues in which they looked at the role of high-dose retinoic acid in the treatment of leukoplakia found that 67% f the treatment group showed a response compared with only 10% of the control group. Other studies have shown that there may be a propensity for remission once the treatment has been stopped.

β-Carotene is a member of the carotenoids, which are highly pigmented (red, orange, yellow), fat-soluble compounds naturally present in many fruits, grains, oils, and vegetables (green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers). α-, β-, and γ-carotene are considered provitamins because they can be converted to active vitamin A. β-Carotene supplements alone have been associated with clinical improvement; rates have ranged from 14.8% to 71%. Unlike the retinoids, there have been no side effects reported in patients given β-carotene supplements. However, little is known about recurrence rates after treatment.