In 1988, Blot and colleagues reported results from a U.S. case–control study of oral cavity or pharyngeal (oropharyngeal and hypopharyngeal) cancers, with results showing independent associations of smoking and alcohol with increased risk, multiplicative interaction effects between smoking and alcohol, and that nearly three-quarters of these cancers are attributable to smoking and alcohol. The report by Blot and colleagues represents a landmark in oropharyngeal cancer epidemiology. This study, the largest at the time, introduced several novel concepts in oropharyngeal cancer epidemiology that remain relevant today—etiologic heterogeneity, statistical interaction effects, adjusted attributable fractions, and disparities by sex and race/ethnicity. Perhaps the most significant recognition in the field since 1988 is the etiologic association of human papillomavirus (HPV, primarily HPV16) with cancers arising in the oropharynx. Today, more than 80% of oropharyngeal cancers in the United States are caused by HPV while only approximately 3% of oral cavity cancers are caused by HPV. This etiologic heterogeneity across head and cancer subsites revealed by HPV is manifest at the genetic/genomic, epidemiologic, and clinical levels. Tobacco and alcohol remain the major etiologic factors for oral cavity cancers while HPV is the major cause of oropharyngeal cancers. Thus, tobacco and alcohol control and prophylactic HPV vaccination remain the most promising prevention tools for oral cavity and oropharyngeal cancers at this time. Importantly, the ever-emerging alternative tobacco products, such as smokeless tobacco/snus, hookah and water pipes, e-cigarettes, flavored cigars and cigarillos, and oral dissolvable products, represent a key public health concern and the carcinogenic effects of these products remains an active area of investigation. See related article by Blot and colleagues, Cancer Res 1988;48:3282–7

中文翻译：

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口腔癌和口咽癌流行病学的演变

1988 年，Blot 及其同事报告了美国口腔癌或咽癌（口咽癌和下咽癌）病例对照研究的结果，结果显示吸烟和饮酒与风险增加存在独立关联，吸烟和饮酒之间存在乘法相互作用效应，并且近四分之三的癌症是由吸烟和酗酒造成的。Blot 及其同事的报告代表了口咽癌流行病学的里程碑。这项当时规模最大的研究引入了口咽癌流行病学中的几个新概念，这些概念至今仍然具有相关性——病因异质性、统计相互作用效应、调整后的归因分数以及性别和种族/民族的差异。也许自 1988 年以来该领域最重要的认识是人乳头瘤病毒（HPV，主要是 HPV16）与口咽癌的病因学关联。如今，美国超过 80% 的口咽癌是由 HPV 引起的，而只有约 3% 的口腔癌是由 HPV 引起的。HPV 揭示的头部和癌症亚位点的病因学异质性体现在遗传/基因组、流行病学和临床水平上。烟草和酒精仍然是口腔癌的主要病因，而HPV是口咽癌的主要原因。因此，控制烟酒和预防性HPV疫苗接种仍然是目前口腔癌和口咽癌最有希望的预防工具。重要的是，不断出现的替代烟草产品，无烟烟草/鼻烟、水烟和水烟、电子烟、调味雪茄和小雪茄以及口腔可溶解产品等是一个关键的公共卫生问题，这些产品的致癌作用仍然是一个活跃的研究领域。参见 Blot 及其同事的相关文章，Cancer Res 1988；48:3282–7