Although tobacco prevalence is declining in most developed countries, less developed countries are still experiencing an increase in tobacco use. Thus the future burden of oral-cavity and oropharyngeal cancers in less developed countries is expected to be heavy. The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is dramatically increasing in the United States and other developed countries, although trends in less developed countries are not clear at present. HPV vaccine compliance in the United States is low, although it continues to increase each year. Increasing the HPV vaccination rate to control future HPV-associated cancer incidence remains a priority.
Key points
- •
Although tobacco prevalence is declining in most developed countries, less developed countries are still experiencing an increase in tobacco use. Thus the future burden of oral-cavity and oropharyngeal cancers in less developed countries is expected to be heavy.
- •
The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is dramatically increasing in the United States and other developed countries, although trends in less developed countries appear unclear at present.
- •
HPV vaccine compliance in the United States is low, although it continues to increase each year.
Evolution of the tobacco epidemic
Each year in the world, approximately 264,000 cases of oral-cavity cancer and 136,000 cases of pharyngeal (including nasopharynx, oropharynx, and hypopharynx) cancer are diagnosed. In the United States, 41,380 cases of oral-cavity and pharyngeal cancer are expected to be diagnosed in 2013, and almost 8000 deaths will be attributed to these diseases in 2013. Unfortunately, a shortcoming common to many national and international databases is that an accurate separation of head and neck cancer statistics into specific subsites (oral cavity vs oropharynx vs hypopharynx vs nasopharynx) is difficult or impossible because many cases are categorized under generic terms such as “tongue” or “palate,” which include both oral cavity (oral tongue and hard palate) and oropharynx (base of tongue and soft palate). In addition, the generic term “pharynx” as commonly used mixes naso-, oro-, and hypopharynx anatomic sites; however, at least 80% of pharyngeal cancers are located within the oropharynx in most countries, with some notable exceptions such as China and Southeast Asia. Tobacco use, including both smoking and chewing of tobacco products, is a well-established risk factor for both oral-cavity and oropharyngeal cancers. Cigarette smoking is generally the most common form of tobacco use, but in certain regions local tobacco products are smoked or chewed. Some examples include smoking bidi or chutta in India, smoking water pipes in North Africa, and smoking kreteks (clove-flavored cigarettes) in Indonesia. Cigarette smoking confers a 4- to 5-fold increase of both oral-cavity and oropharyngeal cancers.
Tobacco as a Risk Factor for Oral Cavity and Pharyngeal Cancers
Approximately 65% of oral-cavity cancers and 66% of pharyngeal cancers (perhaps lower for oropharyngeal cancers and higher for hypopharyngeal cancers) are attributed to tobacco smoking. Thus tobacco use can be considered the most important risk factor for oral-cavity and pharyngeal cancers, because the majority of these cancers can be attributed to tobacco use; however, as discussed in this article, human papillomavirus (HPV) may become the principal risk factor for oropharyngeal cancer. The attributable fraction for chewing tobacco varies considerably by region and sex. Among men cases of oral-cavity cancer that are attributed to chewing tobacco are estimated to be 1.6% in Canada, 6.6% in the United States, 52.5% in India, and 68.2% in Sudan. Among women, approximately 13.6% of cases of oral-cavity cancer in Sudan and 51.6% of cases in India were attributed to chewing tobacco.
Tobacco as a Risk Factor Independent of Alcohol
Tobacco use is a risk factor independent of alcohol drinking, as demonstrated by studies focusing on individuals who had never drank alcohol. When estimating the effect of tobacco use on the risk of oral-cavity and pharyngeal cancer, the effect of alcohol drinking is a concern because it could bias the estimation. Thus alcohol drinking may act as a confounder, because it is a risk factor of the disease and is associated with the exposure of tobacco use. Even when alcohol drinking is adjusted for in statistical models, residual confounding is a concern because it is difficult to assess alcohol exposures over a lifetime. One solution to this issue would be to estimate the effect of tobacco use among those who never drink alcohol, but gathering sufficient patients with oral-cavity and pharyngeal cancer who are not alcohol drinkers has been very difficult. The consortium approach, with collaborations of researchers across studies to pool data has been useful in addressing this issue. The International Head and Neck Cancer Epidemiology (INHANCE) consortium pooled data across 14 case-control studies including 717 patients with oral-cavity cancer and 380 with pharyngeal cancer (both oropharynx and hypopharynx) who were never drinkers. Never drinkers who had smoked for more than 40 years had a 3-fold increase in risk for oral-cavity cancer and an almost 5-fold increase in risk for pharyngeal cancer.
Tobacco and Alcohol Interaction
An interaction between tobacco and alcohol is well established for oral-cavity and pharyngeal cancers. An INHANCE consortium analysis of 2992 cases of oral-cavity cancer and 16,152 controls demonstrated an interaction between tobacco and alcohol on the multiplicative scale. The multiplicative interaction parameter for oral-cavity cancer was 3.1 (95% confidence interval [CI] 1.8–5.2), suggesting that the interaction observed was almost 3-fold greater than the product of the individual effects of tobacco and alcohol. Similarly, for pharyngeal cancer, an analysis of 4038 cases (including both oropharyngeal and hypopharyngeal cancer) and 16,152 controls showed that there was an interaction on the multiplicative scale between tobacco and alcohol, with a multiplicative interaction parameter of 1.9 (95% CI 1.4–2.6). The assessment of attributable fraction for tobacco and alcohol combined showed that most cases would be attributed to tobacco alone or a combination of tobacco and alcohol, whereas very few cases would be attributed to alcohol alone.
Tobacco Epidemic and Variation by Country
In high-income countries, tobacco prevalence has been decreasing over the last several decades, owing to the antismoking campaigns. The tobacco epidemic has been described in 4 stages :
- •
Stage 1 reflects the beginning of the epidemic with cigarette smoking prevalence less than 20%
- •
Stage 2 shows an increase in the prevalence to around 40% to 80%
- •
Stage 3 is characterized by a plateau and beginning decline in prevalence
- •
Stage 4 shows a final decline in the prevalence
Thus, high-income countries are in stage IV, or the last stage, for both men and women, with an overall tobacco prevalence of 30% among men and 19% among women. In the United States, the male tobacco prevalence decreased from 52% in 1960 to 22% in 2010. Among American women, the tobacco prevalence decreased from 34% in 1960% to 17% in 2010. The major concern is that the low-income and middle-income countries are in stages I and II of the tobacco epidemic, respectively, with prevalence expected to continue to increase. In middle-income countries, the overall male prevalence of tobacco smoking is 34% and the overall female prevalence is 5%. In low-income countries, the male prevalence of tobacco smoking is approximately 21% and the female prevalence is 3%.
Variation in Oral-Cavity and Oropharyngeal Cancer Burden by Country
Cancer is already a major burden in low-income and middle-income countries, and the burden is expected to increase in the next decades because of the growing population, adoption of health behaviors of high-income countries, and a decrease in competing risk of infectious diseases. The future burden of oral-cavity and pharyngeal cancers on lower-income countries is expected to increase greatly based just on demographic effects, with an 80% increase in cases of oral-cavity cancer and an 84% increase in cases of pharyngeal cancer. The projected number of cases of oral-cavity cancer in less developed countries for the year 2030 (307,735) is much greater than the projected number of cases of pharyngeal cancer (161,929). If the tobacco epidemic in the less developed countries is further accounted for in the projections, the case numbers are expected to be a heavy burden. Focusing on the countries with the highest male tobacco-smoking prevalences in the world ( Table 1 ), also representing chiefly low-income and middle-income countries, the projected number based on demographic effects again show large increases, although they do not yet have the highest incidence rates in the world. Dramatic increases in cases of oral-cavity and pharyngeal cancer are expected for Papua New Guinea (122%), Tunisia (82%), China (71%), and Albania (63%).
| Country | Currently Smoking Any Tobacco Product | Oral-Cavity and Pharyngeal Cancer Incidence Rates (per 100,000) in 2008 b | Oral-Cavity and Pharyngeal Cancer Incident Cases | % Change from 2008 to 2030 | ||
|---|---|---|---|---|---|---|
| Male | Female | 2008 | 2030 Projection | |||
| Greece | 63 | 41.4 | 2.0 | 496 | 651 | 31.3 |
| Albania | 60.1 | 19.4 | 8.4 | 334 | 545 | 63.2 |
| Russian Federation | 59.4 | 23.9 | 6.7 | 14190 | 16278 | 14.7 |
| Papua New Guinea | 57.7 | 30.8 | 27.2 | 883 | 1957 | 121.6 |
| Indonesia | 61.3 | 3.7 | 3.4 | 6939 | 12907 | 86.0 |
| Georgia | 56.6 | 5.7 | 1.9 | 122 | 133 | 9.0 |
| Tunisia | 52.7 | 3.6 | 2.8 | 271 | 493 | 81.9 |
| Armenia | 50.9 | 2.1 | 2.4 | 97 | 127 | 30.9 |
| China | 50.4 | 2.1 | 1.4 | 22134 | 37838 | 70.9 |
| Latvia | 50.1 | 22.3 | 5.4 | 208 | 236 | 14.4 |
From the perspective of incidence rates, the highest incidence rates of oral-cavity and pharyngeal cancer are observed in:
- •
Papua New Guinea (27 per 100,000)
- •
Chinese Taipei (21 per 100,000)
- •
Maldives (21 per 100,000)
- •
Hungary (18 per 100,000)
- •
Bangladesh (14 per 100,000)
Thus the countries with high smoking prevalence observed in Table 1 are not consistently those with the highest incidence rates of oral-cavity and pharyngeal cancer; however, there is likely a time lag for the effect of the tobacco epidemic to be observed in cancer incidence rates. This observation also highlights that the etiology of oral-cavity and pharyngeal cancer is complex and multifactorial, including other important risk factors such as alcohol drinking, HPV infection, and chewing other products such as betel quid and areca nut (with or without tobacco). The high incidence rates observed in Central Europe are thought to be due to the combined high prevalence of smoking and alcohol drinking among men, whereas in Taiwan, betel quid and areca nut chewed without tobacco may be the main cause of the high incidence rates of oral-cavity and pharyngeal cancer.
Evolution of the tobacco epidemic
Each year in the world, approximately 264,000 cases of oral-cavity cancer and 136,000 cases of pharyngeal (including nasopharynx, oropharynx, and hypopharynx) cancer are diagnosed. In the United States, 41,380 cases of oral-cavity and pharyngeal cancer are expected to be diagnosed in 2013, and almost 8000 deaths will be attributed to these diseases in 2013. Unfortunately, a shortcoming common to many national and international databases is that an accurate separation of head and neck cancer statistics into specific subsites (oral cavity vs oropharynx vs hypopharynx vs nasopharynx) is difficult or impossible because many cases are categorized under generic terms such as “tongue” or “palate,” which include both oral cavity (oral tongue and hard palate) and oropharynx (base of tongue and soft palate). In addition, the generic term “pharynx” as commonly used mixes naso-, oro-, and hypopharynx anatomic sites; however, at least 80% of pharyngeal cancers are located within the oropharynx in most countries, with some notable exceptions such as China and Southeast Asia. Tobacco use, including both smoking and chewing of tobacco products, is a well-established risk factor for both oral-cavity and oropharyngeal cancers. Cigarette smoking is generally the most common form of tobacco use, but in certain regions local tobacco products are smoked or chewed. Some examples include smoking bidi or chutta in India, smoking water pipes in North Africa, and smoking kreteks (clove-flavored cigarettes) in Indonesia. Cigarette smoking confers a 4- to 5-fold increase of both oral-cavity and oropharyngeal cancers.
Tobacco as a Risk Factor for Oral Cavity and Pharyngeal Cancers
Approximately 65% of oral-cavity cancers and 66% of pharyngeal cancers (perhaps lower for oropharyngeal cancers and higher for hypopharyngeal cancers) are attributed to tobacco smoking. Thus tobacco use can be considered the most important risk factor for oral-cavity and pharyngeal cancers, because the majority of these cancers can be attributed to tobacco use; however, as discussed in this article, human papillomavirus (HPV) may become the principal risk factor for oropharyngeal cancer. The attributable fraction for chewing tobacco varies considerably by region and sex. Among men cases of oral-cavity cancer that are attributed to chewing tobacco are estimated to be 1.6% in Canada, 6.6% in the United States, 52.5% in India, and 68.2% in Sudan. Among women, approximately 13.6% of cases of oral-cavity cancer in Sudan and 51.6% of cases in India were attributed to chewing tobacco.
Tobacco as a Risk Factor Independent of Alcohol
Tobacco use is a risk factor independent of alcohol drinking, as demonstrated by studies focusing on individuals who had never drank alcohol. When estimating the effect of tobacco use on the risk of oral-cavity and pharyngeal cancer, the effect of alcohol drinking is a concern because it could bias the estimation. Thus alcohol drinking may act as a confounder, because it is a risk factor of the disease and is associated with the exposure of tobacco use. Even when alcohol drinking is adjusted for in statistical models, residual confounding is a concern because it is difficult to assess alcohol exposures over a lifetime. One solution to this issue would be to estimate the effect of tobacco use among those who never drink alcohol, but gathering sufficient patients with oral-cavity and pharyngeal cancer who are not alcohol drinkers has been very difficult. The consortium approach, with collaborations of researchers across studies to pool data has been useful in addressing this issue. The International Head and Neck Cancer Epidemiology (INHANCE) consortium pooled data across 14 case-control studies including 717 patients with oral-cavity cancer and 380 with pharyngeal cancer (both oropharynx and hypopharynx) who were never drinkers. Never drinkers who had smoked for more than 40 years had a 3-fold increase in risk for oral-cavity cancer and an almost 5-fold increase in risk for pharyngeal cancer.
Tobacco and Alcohol Interaction
An interaction between tobacco and alcohol is well established for oral-cavity and pharyngeal cancers. An INHANCE consortium analysis of 2992 cases of oral-cavity cancer and 16,152 controls demonstrated an interaction between tobacco and alcohol on the multiplicative scale. The multiplicative interaction parameter for oral-cavity cancer was 3.1 (95% confidence interval [CI] 1.8–5.2), suggesting that the interaction observed was almost 3-fold greater than the product of the individual effects of tobacco and alcohol. Similarly, for pharyngeal cancer, an analysis of 4038 cases (including both oropharyngeal and hypopharyngeal cancer) and 16,152 controls showed that there was an interaction on the multiplicative scale between tobacco and alcohol, with a multiplicative interaction parameter of 1.9 (95% CI 1.4–2.6). The assessment of attributable fraction for tobacco and alcohol combined showed that most cases would be attributed to tobacco alone or a combination of tobacco and alcohol, whereas very few cases would be attributed to alcohol alone.
Tobacco Epidemic and Variation by Country
In high-income countries, tobacco prevalence has been decreasing over the last several decades, owing to the antismoking campaigns. The tobacco epidemic has been described in 4 stages :
- •
Stage 1 reflects the beginning of the epidemic with cigarette smoking prevalence less than 20%
- •
Stage 2 shows an increase in the prevalence to around 40% to 80%
- •
Stage 3 is characterized by a plateau and beginning decline in prevalence
- •
Stage 4 shows a final decline in the prevalence
Thus, high-income countries are in stage IV, or the last stage, for both men and women, with an overall tobacco prevalence of 30% among men and 19% among women. In the United States, the male tobacco prevalence decreased from 52% in 1960 to 22% in 2010. Among American women, the tobacco prevalence decreased from 34% in 1960% to 17% in 2010. The major concern is that the low-income and middle-income countries are in stages I and II of the tobacco epidemic, respectively, with prevalence expected to continue to increase. In middle-income countries, the overall male prevalence of tobacco smoking is 34% and the overall female prevalence is 5%. In low-income countries, the male prevalence of tobacco smoking is approximately 21% and the female prevalence is 3%.
Variation in Oral-Cavity and Oropharyngeal Cancer Burden by Country
Cancer is already a major burden in low-income and middle-income countries, and the burden is expected to increase in the next decades because of the growing population, adoption of health behaviors of high-income countries, and a decrease in competing risk of infectious diseases. The future burden of oral-cavity and pharyngeal cancers on lower-income countries is expected to increase greatly based just on demographic effects, with an 80% increase in cases of oral-cavity cancer and an 84% increase in cases of pharyngeal cancer. The projected number of cases of oral-cavity cancer in less developed countries for the year 2030 (307,735) is much greater than the projected number of cases of pharyngeal cancer (161,929). If the tobacco epidemic in the less developed countries is further accounted for in the projections, the case numbers are expected to be a heavy burden. Focusing on the countries with the highest male tobacco-smoking prevalences in the world ( Table 1 ), also representing chiefly low-income and middle-income countries, the projected number based on demographic effects again show large increases, although they do not yet have the highest incidence rates in the world. Dramatic increases in cases of oral-cavity and pharyngeal cancer are expected for Papua New Guinea (122%), Tunisia (82%), China (71%), and Albania (63%).
