Although oral cancer undoubtedly has a multifaceted etiology, tobacco use and alcohol consumption are widely considered to be its major risk factors. Over the past 30 years, a series of authoritative reports issued by the U.S. government and various international health agencies have conclusively established that tobacco use, especially cigarette smoking, is causally related to at least 8 major cancer sites and increases the mortality rate for several others. Although other lifestyle and environmental factors also have been identified as risk factors for oral cancer, tobacco use remains the single most important and preventable cause of this disease.

A. State of the Science

Cigarettes

Reports by the U.S. Public Health Service have clearly established a direct causal relationship between cigarette smoking and cancer of the oral cavity. A number of major prospective cohort mortality studies have been critical in both elucidating the causal nature of the association and estimating the magnitude of the disease burden. Two such studies, Cancer Prevention Study (CPS) I and II, sponsored by the American Cancer Society (ACS), are the largest epidemiological studies ever undertaken, each following more than 1 million men and women. Evidence from these and other epidemiological studies has provided key documentation of the association between cigarette smoking and oral cancer.

The mortality risk for oral cancer in cigarette smokers is substantially greater than that observed among life long “never smokers.” Although estimates vary, most studies have reported mortality ratios for smokers versus never smokers of about 5-6:1, with several reporting ratios in excess of 10:1. Furthermore, the risk for death from oral cancer is consumption related; the more cigarettes consumed daily and the more years one has smoked, the greater the risk.

In CPS II, which followed over 1.2 million individuals for 6 years beginning in 1982, male cigarette smokers had a relative risk for oral cancer 27.7 times greater than that of a male never smoker; the rates among women who smoked were nearly 6 times greater. Estimates of the percentage of oral cancers attributable to cigarette smoking have been quite consistent, generally ranging from 75% to 90%.

A recent analysis conducted for the President’s Cancer Panel on Avoidable Causes of Cancer estimated that 80% of all oral cancer deaths (International Classification of Disease Codes 140-149) expected to occur in 1995 would be directly attributable to cigarette smoking, 91% among men and almost 60% among women. These estimates do not consider the possible interaction between smoking and other risk factors and, therefore, may overestimate the impact of smoking. Conversely, however, these estimates do not include those oral cancers that result from non-cigarette tobacco use such as pipe and cigar smoking and the use of snuff and chewing tobacco.

Numerous studies examining the relative risk for oral cancer among former smokers have found that the risk for oral cancer was lower among former smokers after the first few years of abstinence than for those who continued to smoke. These studies have found that after 3 to 5 years of smoking abstinence, oral cancer risk decreased by about 50%.

Cigars and Pipes

Although cigarette smoking is the form of tobacco use most often linked with increased incidence of oral cancer, regular use of pipes or cigars also increases the risk of disease. Both prospective and retrospective studies have consistently documented that pipe and cigar smokers experience mortality rates for oral cancer either similar or higher than those risks observed among cigarette smokers. A 1982 Surgeon General’s Report, The Health Consequences of Smoking: Cancer, concluded:

Cigarette smoking is a major cause of cancers of the oral cavity in the United States. Individuals who smoke pipes or cigars experience a risk for oral cancer similar to that of the cigarette smoker.

Smokeless Tobacco (Snuff and Chewing Tobacco)

Only recently has the scientific and public health community turned its attention to the possible health implications of smokeless tobacco use. In 1981, Winn and colleagues published a seminal study involving 255 women living in rural North Carolina ; they found a four fold increased risk of oral cancer among nonsmokers who dipped snuff. This association could not be explained by smoking or alcohol consumption, dentures, poor dentition, diet, or use of mouthwash. For long- term users there was a 50-fold increased risk for cancer of the gum and buccal mucosa. Even women who had used smokeless tobacco less than 25 years had a 14-fold greater risk for these cancers (Table 1). In 1982, the following statement was published in the Report of the Surgeon General, the Health

Consequences of Smoking: Cancer:

Long term use of snuff appears to be a factor in the development of cancers of the oral cavity, particularly cancers of the cheek and gum.

Table 1: Estimated Relative Risk of Oropharyngeal Cancer According to Duration of Snuff Use and Site

Anatomic Site

Duration of Snuff
Use (yrs)

Relative Risk

Gum and Buccal Mucosa

0
24
25-49
~ 50

1.0
13.8
12.6
48.0

Other Mouth and Pharynx

0
1-24
25-49
~ 50

1.0
1.7
3.8
1.3

The Winn study was one of the first to provide strong evidence for a causal relationship between smokeless tobacco use and oral cancer. As results from other studies began to emerge, the National Cancer Advisory Board (NCAB) of the National Cancer Institute issued a resolution on smokeless tobacco in 1985, which stated that the NCAB “considers the use of smokeless tobacco to pose a serious and increasing health risk.” In September 1985, the International Agency for Research on Cancer (IARC) issued its own report on smokeless tobacco, which concluded:

In aggregate, there is sufficient evidence that oral use of smokeless tobacco is carcinogenic to humans.

In April of the following year, the Surgeon General released a report during Congressional testimony (22) on new legislation for labeling smokeless tobacco. The overall conclusion of this comprehensive review clearly established the use of smokeless tobacco as a health risk:

After a careful examination of the relevant epidemiologic, experimental, and clinical data, the committee concludes that the oral use of smokeless tobacco represents a significant health risk. It is not a safe substitute for smoking cigarettes. It can cause cancer and a number of noncancerous oral conditions and can lead to nicotine addiction and dependence.

The report also reached a number of conclusions regarding smokeless