Head and Neck Cancer Risk Prediction Model

描述(由申请人提供)：国际头颈癌流行病学联合会(INHANCE)报告称，在拉丁美洲(83%)和欧洲(84%)的病例中，烟草和酒精的使用占很大比例，但在美国，头颈部癌症(HNC)病例中只有51%是烟酒使用。女性吸烟和饮酒的人群归因风险(57%)低于男性(74%)，年轻受试者(33%)低于年长受试者(73%)。近年来，美国年轻女性的扁桃体和舌癌以及口腔和咽癌的发病率一直在以惊人的速度增长，这可能在一定程度上是由于人类乳头瘤病毒(HPV)感染。由于烟草、酒精和HPV不太可能是所有HNC病例的原因，因此必须继续调查其他风险因素。此外，癌症风险预测模型可能有助于针对高危人群的个性化预防策略，例如年轻的HPV阳性个人和有HNC家族史的个人。我们建议在INHANCE联合会数据库中开发HNC风险预测模型，该数据库包含来自27项研究的18,000个病例和28,000个对照。我们的具体目标是：1)通过汇集更多关于职业暴露和口腔卫生的数据对风险因素进行全面分析，并在INHANCE联盟中按地理区域估计它们相应的归因风险；2)利用AIM 1的结果和SEER数据得出的基线癌症风险比率，开发美国HNC以及口腔、口咽癌、下咽和喉癌的首个风险预测模型；以及3)验证队列联盟在美国队列中的HNC风险预测模型。竞争风险模型将被用来估计在5年、10年和20年的时间间隔内发生这些癌症的可能性。接受调查的危险因素将包括吸烟、饮酒、HNC家族史、HPV感染、选择的基因变异、非自愿吸烟、性行为、口腔卫生、饮食因素、体力活动、社会经济状况、职业暴露和BMI。我们将通过比较预期和观察的癌症病例数量以及使用队列联盟的队列数据绘制的ROC曲线来验证预测模型。我们的HNC风险预测模型将具有以下潜在用途：1)未来在个性化医学背景下的临床应用；2)牙医在决定是否继续进行常规可视化检查以外的口腔癌症检查时的决策；3)供有兴趣了解其HNC风险的个人(即有HNC家族病史的个人)公开使用；以及4)用于研究用途，以选择高危人群进行初级预防研究。此外，预测模型可以作为评估风险降低的工具，供个人评估行为改变(即戒烟或减少饮酒)的影响。INHANCE联合体中多学科调查人员的大规模合作为该项目提供了一个难得的机会，该项目将为HNC提供全面的风险因素评估和风险预测模型。

DESCRIPTION (provided by applicant): The International Head and Neck Cancer Epidemiology (INHANCE) Consortium reported that tobacco and alcohol use account for a large proportion of cases in Latin America (83%) and Europe (84%) but only 51% of head and neck cancer (HNC) cases in the United States. The population attributable risks for tobacco and alcohol were lower for women (57%) than men (74%), and lower for younger subjects (33%) than older subjects (73%). In recent years, tonsillar and tongue cancer incidence, and oral cavity and pharyngeal cancer incidence in young women have been increasing at alarming rates in the US, which may partly be due to human papillomavirus (HPV) infection. Since it is unlikely that tobacco, alcohol and HPV account for all HNC cases, other risk factors must continue to be investigated. Furthermore, cancer risk prediction models may aid in personalized prevention strategies targeted to high risk populations such as young HPV positive individuals and individuals with family history of HNC. We propose to develop HNC risk prediction models within the INHANCE Consortium database of 18,000 cases and 28,000 controls from 27 studies. Our specific aims are: 1) to conduct a comprehensive analysis of risk factors by pooling additional data on occupational exposures and oral hygiene, and to estimate their corresponding attributable risks by geographic region in the INHANCE Consortium; 2) to develop the first risk prediction models for HNC and for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancer for the US, using aim 1 results and baseline cancer hazard rates derived from SEER data; and 3) to validate the HNC risk prediction model in US cohorts from the Cohort Consortium. Competing risk models will be used to estimate the probability of developing these cancers over a 5-, 10-, and 20-year time interval. The risk factors under investigation will include tobacco smoking, alcohol drinking, family history of HNC, HPV infection, select genetic variants, involuntary smoking, sexual behaviors, oral hygiene, dietary factors, physical activity, socioeconomic status, occupational exposures, and BMI. We will validate the prediction models by comparing the expected and observed number of cancer cases, and ROC curves using cohort data from the Cohort Consortium. Our HNC risk prediction models will have the potential for: 1) clinical use within the context of personalized medicine in the future, 2) for dentists in decision making on whether to proceed with oral cancer exams beyond conventional visualization examination, 3) for public use by individuals interested in understanding their HNC risk (ie, individuals who have family history of HNC), and 4) for research use to select high risk populations for studies of primary prevention. Additionally, the prediction model can serve as a tool to estimate risk reduction for individuals to evaluate the impact of behavior modification (i.e., quitting cigarette smoking or reducing alcohol drinking). The large collaboration of multidisciplinary investigators in the INHANCE Consortium provides an exceptional opportunity for this project on comprehensive risk factor evaluation and risk prediction models for HNC.