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In large parts of the world, esophageal cancer is a very common disease, and the potential for cure is worse than for most other malignancies. The remarkably uneven geographic distribution, and the apparently small proportion that can be attributed to genetic factors, seem to imply that strong external risk factors—possibly reinforced by genetically determined susceptibility—are in operation. The dramatic rise in incidence of the adenocarcinomas poses a special challenge to epidemiologists. Such a rapid change is bound to depend on changes in the exposure to important causal factors. The well documented increase in the prevalence of obesity in many populations might be one such factor. However, there are many conflicting observations and there is clearly room for alternative hypotheses. It appears that a number of other promising leads need be followed up, requiring joint and decisive efforts by epidemiologists and basic scientists.

Keratinocyte cancers (KC) include basal and squamous cell carcinomas that arise from keratinocytes or their precursors. KCs are the most common malignancies in humans. Basal cell carcinoma (BCC) has higher incidence rates, but squamous cell carcinoma (SCC) causes most deaths. Despite increasing incidence rates, the mortality rates have not changed markedly in recent years. The geographic and demographic features of these tumors have remained consistent over the past several decades, with a gradient of increasing incidence rates with proximity to the equator, predominantly affecting fair-skinned populations. Risk increases with age, is higher in men than women, and is associated with artificial as well as natural exposure to UV light. There is emerging evidence that these malignancies, particularly BCCs, may be increasing in younger adults and among women. While basal and squamous cell carcinomas share etiological factors, the relative importance of these factors, pattern of exposure, molecular alterations, and even the factors themselves differ.

Esophageal cancer shows distinct geographic distributions, changing incidence rates, and primary risk factors when examined separately as squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma remains the dominant histologic type in many low- and middle-income countries and occurs frequently, while adenocarcinoma is classified as rare but predominates in Western countries. Tobacco and alcohol are the dominant risk factors for squamous cell carcinoma in Western countries, but not in high-incidence Asian populations, where hot beverages and specific nutritional deficiencies may be important. For adenocarcinoma, tobacco use is causal while alcoholic beverages are not. Rather, obesity and gastroesophageal reflux disease are the other dominant identified risk factors. Genetic predisposing factors and somatic mutations are also cell type specific. The differences in esophageal cancer incidence within and between countries, by sex and race, and in known risk factors suggest major strides in understanding the etiology of esophageal cancer is within reach.

This chapter reviews the epidemiology of esophageal cancer. It describes the known and suspected causes of esophageal cancer, with emphasis on the differences in risk factors between adenocarcinoma and squamous cell carcinoma of the esophagus. Since treatment successes have been limited and esophageal cancers still are usually fatal, regardless of cell type, epidemiologic patterns may offer clues to prevention.

Variants of invasive squamous carcinoma of the anal canal and perianal skin, referred to collectively as anal cancers, are rare malignancies constituting approximately 2% of all intestinal cancers. of a crude estimate of 35,000–40,000 new anal cancers worldwide, approximately 3,300 cases are diagnosed in the United States each year. This chapter reviews the epidemiology of anal cancer. Topics covered include classification, demographic patterns, lifestyle and environmental factors, host factors, pathogenesis, and preventive measures.

This chapter discusses skin and soft tissue tumours. Three known skin tumours are the basal cell carcinoma, the squamous cell carcinoma, and the melanoma. Basal cell carcinoma or rodent ulcer predominantly affects the elderly and is rarely a clinical problem except in a few neglected cases and in cases where there is an extensive invasion of the local soft tissues and bones. Squamous carcinoma emerges in middle-aged and elderly patients. Compared to basal cell carcinoma, squamous carcinoma spreads in the local and regional nodes and may develop blood-borne metastases. Melanoma, the most potent of the three skin tumours affects any age, although it is rare in children. It is associated with excessive sun exposure. This disease has rapid blood-borne metastases and can cause rapid death.

Cancer of the esophagus is the eighth most common malignancy worldwide in terms of incident cases and the sixth most common for cancer deaths. The two main histopathologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC), have strikingly different clinical and epidemiologic features. ESCC occurs throughout the esophagus and is the most common histologic subtype globally; over 90% of cases in the traditionally high-risk regions of Eastern Asia and Eastern and Southern Africa are ESCC. The incidence of ESCC is decreasing worldwide. In some high-risk areas in Asia the decrease was preceded by economic development and improvements in diet, whereas in high-income countries the decrease followed reductions in cigarette smoking. In contrast, the incidence of EADC continues to increase in many high- and middle-income countries, especially among white men. EADC develops in the lower third of the esophagus, primarily because of gastroesophageal reflux disease (GERD) and obesity.

This chapter discusses the most common and best-studied histologic type of laryngeal cancer: squamous cell carcinoma of the larynx. Topics covered include classification, demographic patterns, environmental factors, host factors, and preventive measures.

The distinctive racial/ethnic and geographic distribution of NPC worldwide suggests that both environmental factors and genetic traits contribute to its development. Well-established risk factors for NPC include elevated antibody titers against the EBV, circulating EBV DNA, consumption of salt-preserved fish, and a family history of NPC. Consumption of other preserved foods, tobacco smoking, a history of chronic respiratory tract conditions, and certain HLA genotypes may be associated with elevated NPC risk, whereas consumption of fresh fruits and vegetables and other HLA genotypes may be associated with decreased risk. Evidence for a causal role of various inhalants, herbal medicines, and occupational exposures is inconsistent. Other than dietary modification, no concrete preventive measures for NPC exist. Comprehending how viral, genetic, and environmental factors interact to cause NPC will illuminate the pathways by which this malignancy develops, as well as how it may be prevented.

This chapter reviews studies on the link between smoking and cancer of the oesophagus. In 2002, it was estimated that there were 315,000 new cases of oesophageal cancer (OC) among men and 145,000 among women worldwide. The two major histologic types are squamous cell carcinoma of the oesophagus (SCCO) and adenocarcinoma of the oesophagus (ACO), which account for over 90% of OC. The vast majority of OC are SCCO. Over recent periods, however, a levelling off or decreases in SCCO incidence rates, and increases in ACO incidence rates have been observed in the United States, Canada, and several European countries, especially Northern European ones, and in a few other areas.

Anal canal cancer is a generally uncommon cancer that has been increasing in incidence for several decades. In most geographic locations, squamous cell carcinoma (SCC) accounts for 70% or more of cases, and incidence is slightly higher in women than in men. The remaining cases are mainly adenocarcinoma, but the degree to which this represents misclassified rectal cancer is uncertain. In almost all cases, anal SCC is caused by persistent infection with high-risk types of human papillomavirus (HPV); HPV-16 accounts for 75% or more of all cases. Survival is highly stage-dependent, and cure is usual if the cancer is diagnosed early. The main risk factor is anal exposure to HPV, and for this reason homosexual men are at particularly high risk. In women, risk is increased in those with higher numbers of sexual partners, and in those with a history of HPV-related disease at genital sites.

Ultraviolet (UV) radiation is the principal cause of over 95% of keratinocyte cancers (basal cell carcinomas and squamous cell carcinomas of the skin), the most common cancers in white populations worldwide. UV radiation also causes an estimated 60%–90% of cutaneous melanoma, the cancer affecting the skin’s pigment-producing cells. In addition, UV radiation is the major cause of many eye diseases, including ocular cancers and cataract, the commonest cause of blindness, and is responsible for the underlying changes in skin aging, on which billions of dollars are spent annually in efforts to repair the damage. The sun is the principal source of human exposure to UV radiation. However, artificial sources are encountered in a wide range of industrial and medical settings, and increasingly from commercial tanning facilities. By the late twentieth century, nearly epidemic increases in skin cancer incidence had occurred in white populations, especially in Australia and New Zealand.