ABSTRACT: Characterizing the epidemiology of head and neck cancers is challenging and has received limited attention in the medical literature. Traditionally, 80%–90% of head and neck squamous cell carcinomas (HNSCCs) have been attributed to tobacco and alcohol(Drug information on alcohol) use, but with growing public awareness and tobacco control efforts over the past few decades, there has been a downward trend in smoking prevalence in the US. There is also emerging evidence that human papillomavirus (HPV) is responsible for inconsistencies in HNSCC trends, with oncogenic HPV DNA found in approximately half of oropharyngeal cancers and in a high proportion of oropharyngeal cancers in nonsmokers and nondrinkers. The risk to HNSCC epidemiology is that whatever gains continue to be made in tobacco control may become lost in the increasing numbers of oropharyngeal cancers due to HPV. The purpose of this review is to explore the changing epidemiology of HNSCC, focusing on how it has been shaped by health policy and advocacy interventions and how it will continue to have public health implications in the future, particularly in considering preventive strategies against HPV. Given that the majority of HNSCCs are the result of exposure to preventable public health risks, more focus should be given to this area.
Head and neck cancer encompasses malignant tumors arising within the upper aerodigestive tract. The number of new cases of head and neck cancer in the United States was 48 in 2009, accounting for 3.2% of all new cancers and 2.0% (11,260) of all cancer deaths. Worldwide, an estimated 644,000 new cases are diagnosed each year, with two-thirds of these occurring in developing countries. The median age at diagnosis is in the sixth decade of life, and the incidence is three-fold higher in men. Despite this overall burden, the epidemiology of head and neck cancers receives limited attention in the medical literature.
Every tissue type is represented in the head and neck: from skin to bony paranasal sinuses, salivary glands to lymphoid tonsils, and laryngeal cartilage and joints to pharyngeal epithelium. More than 90% of head and neck cancers are squamous cell carcinomas, which originate from the mucosal surfaces of the lip and oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. These are a heterogeneous group of cancers with unique epidemiologic, histopathologic, and treatment considerations. As most patients with HNSCC present with advanced-stage locoregional disease, its treatment requires a multidisciplinary approach involving otolaryngologists, medical oncologists, radiation oncologists, speech therapists, pathologists, dentists, oral surgeons, and radiologists.
While surgical resection with or without adjuvant radiotherapy had been the mainstay of HNSCC treatment, the concept of organ and function preservation has developed over the past two decades. This involves sparing as much of an organ as possible so that it remains functional, while maintaining or exceeding survival rates of non–organ-preserving strategies.[3,4] Although the majority of patients rank being cured as their top priority, up to 25% of HNSCC patients place a greater emphasis on issues related to quality of life. The treatment strategies that have been developed to accomplish this organ and function preservation include concomitant chemoradiotherapy, intensity-modulated radiation therapy, improved surgical techniques with innovative reconstruction strategies, and molecular-targeted biological agents.
Major Risk Factors for HNSCC
Owing to the vast heterogeneity of cancers arising in the head and neck, characterizing the epidemiology of HNSCC is challenging. Traditionally, 80%–90% of HNSCC have been attributed to tobacco and alcohol use. The risk for developing HNSCC for cigarette smokers is 5- to 25-fold greater than that for nonsmokers, with the risk increasing in a dose-response fashion with frequency, duration, and extent of smoking.[2,6-8] The risk substantially decreases with time from smoking cessation, although this risk never reaches the level of a never-smoker.[9,10] One Italian study found that the cumulative risk at 75 years of age for all upper aerodigestive tract cancers was 6.3% for men who continued to smoke any type of tobacco, 3.1% for men who stopped smoking at around 50 years of age, 1.2% for men who stopped smoking at around 30 years of age, and 0.8% among lifelong nonsmokers. Although active tobacco smoking is the major risk factor for HNSCC, involuntary or secondhand smoking has also been associated with an increased cancer risk. In an international pooled analysis, long exposure to involuntary smoking, described as occurring over a period of more than 15 years, both at home and work, was associated with an increased risk of HNSCC, particularly pharyngeal and laryngeal cancers.
Alcohol has also been shown to synergistically increase the HNSCC risk attributable to tobacco use. Heavy alcohol consumption alone is an independent risk factor for HNSCC. High-frequency use, defined as three or more drinks per day, was independently associated with an increased risk of cancers of the oropharynx, hypopharynx, and larynx. No evidence thus far has established risk differences for various types of alcoholic beverages.
Other risk factors that have been associated with HNSCC include dietary patterns, viruses, and occupational exposures. Numerous studies have associated HNSCC with vitamin A deficiency, whereas other studies describe an inverse association with high fruit and vegetable intake.[2,8] Viruses that have been implicated include Epstein-Barr virus (EBV) and human papillomavirus (HPV), and occupational exposures such as chromium, nickel, and radium have also been linked particularly to sinonasal carcinomas.
Twentieth Century Trends
Throughout the early part of the 20th century, newly diagnosed cases of HNSCC have continued to rise annually, due in part to increasing incidence and improved methods of detection. Over the last two decades, however, there has been a downward trend in HNSCC incidence and mortality, with variability based on anatomic sites. The decline in HNSCC incidence rates has benefited both men and women, as well as all ethnicities, although disparities still remain; African-American males continue to have a higher incidence of oral and oropharyngeal cancers than do white males. Additionally, studies in both high- and low-income countries have demonstrated that patients with low socioeconomic status and low educational attainment had a greater risk for HNSCC, particularly oral cancer.
The overall 5-year survival rate from HNSCC is less than 50%. Although this survival rate has remained unchanged during the past few decades, there is evidence supporting a decrease in HNSCC mortality rates over the last 20 years. Reasons for this downward trend include changes in tumor biology and risk factors, and decreasing HNSCC incidence rates.[6,16] Nevertheless, disparities in survival also remain, with mortality rates among African-American males being approximately twice as high as compared to their white male counterparts. The decline in overall HNSCC incidence and mortality in the United States over the past two decades is likely related to changes in tobacco consumption over the latter half of the 20th century.[6,8]
The Rise and Fall of Big Tobacco—and of Head and Neck Cancer?
Although the tobacco plant is thought to have been growing in the Americas since 6,000 B.C.E., cigarette smoking is largely a 20th century phenomenon.[17,18] From the beginning of the 20th century, cigarettes were widely popular and socially acceptable; by the mid 20th century, however, reports linking cigarette smoking to cancer, heart disease, and other serious health problems led to public efforts to control tobacco smoking.
When Dr. Ernst L. Wynder and others started publishing landmark epidemiologic studies at the turn of the 20th century, linking tobacco smoking to lung cancer and to cancer of the head and neck,[6,17-21] nearly half of all adult Americans—over half of all men and about one-third of all women—were cigarette smokers.[6,17,18] Tobacco companies responded to these initial public health concerns by filtering their cigarettes, to decrease the amount of tar inhaled in the smoke, but in doing so they touted the change as conferring not only a health benefit, but also improving the taste of their cigarettes. In 1961, as a result of growing evidence of the health hazards of smoking, the presidents of the American Cancer Society, American Heart Association, National Tuberculosis Association, and the American Public Health Association submitted a joint letter to President Kennedy, urging him to establish a commission to study the impact of smoking on health. This resulted in the Surgeon General’s Report of 1964, which, based on approximately 7,000 articles related to smoking and disease, reported that cigarette smoking is a cause of lung and laryngeal cancer and concluded that these findings warranted appropriate remedial action.[17,18]
Significant public health efforts to reduce the prevalence of tobacco use began shortly after this 1964 report. In the late 1960s and early 1970s, health warnings on cigarette packs were instituted, there was a nationwide ban on tobacco advertising on television and radio, and antismoking groups responded with antismoking advertisements. For the first time in the 20th century, yearly cigarette consumption began to decline.[17,18]
In more recent years, the growing public awareness and support of tobacco control efforts has had substantial influence in reducing the social acceptability of smoking behavior and continuing the downward trend in tobacco consumption. In the 1990s, tobacco control measures included clean-indoor-air laws, restrictions on tobacco sales to minors, cigarette excise tax increases, and product disclosure laws that require manufacturers to disclose nicotine(Drug information on nicotine) yield and additives.[17,18] In the midst of multiple litigations, the Master Settlement Agreement in November 1998, between big tobacco companies and the attorneys general of 46 states, provided the states with an unprecedented $206 billion industry dollars to promote prevention and control of tobacco use.[6,17] Although the public health advances over the past few decades that have curbed tobacco consumption in the United States are impressive, major disparities such as age, sex, ethnicity, and socioeconomic status still remain, with highest smoking prevalence among younger adults, men, American Indians and Alaskan Natives, and those of lower socioeconomic status.
The decrease in smoking prevalence since the 1970s has been mirrored by a decline in the number of newly diagnosed tobacco-associated cancers.[6,18] This is particularly true for HNSCCs, which have seen an overall decrease in incidence rates that appears to trail the decline in smoking prevalence by 10 to 15 years.
Age-adjusted incidence rates for cancers of the larynx, oral cavity, and hypopharynx have all shown significant decline over the past three decades, but oropharyngeal cancers have not shown a similar decline. Cancers of the oropharynx have been on the rise, now accounting for almost as many cases as the traditional principal sites of HNSCC: the oral cavity and larynx. The increase in oropharyngeal cancer is most dramatic in adults younger than 45 years of age, particularly for cancers of two oropharynx subsites: base of tongue and tonsil.[1,23,24] One recent analysis of Surveillance Epidemiology and End Results (SEER) data from 1973–2001 showed an annual increase in the incidence of oral tongue, base of tongue, and tonsil cancers, by 2.1%, 1.7%, and 3.9%, respectively, in 20- to 44-year-old white patients, while the incidence of HNSCC at other head and neck sites declined. There is emerging evidence that HPV is responsible for these inconsistencies in HNSCC trends.