Head and Neck Cancer Risk Prediction Model

描述（由申请人提供）：国际头颈癌流行病学（INHANCE）联盟报告称，吸烟和饮酒占拉丁美洲（83%）和欧洲（84%）病例的很大比例，但仅占美国头颈癌（HNC）病例的51%。吸烟和饮酒的人群归因风险女性（57%）低于男性（74%），年轻受试者（33%）低于老年受试者（73%）。近年来，美国年轻女性的扁桃体和舌癌发病率以及口腔和咽癌发病率一直以惊人的速度增长，这可能部分是由于人乳头瘤病毒（HPV）感染。由于烟草、酒精和HPV不太可能导致所有HNC病例，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以帮助针对高危人群的个性化预防策略，例如年轻的HPV阳性个体和具有HNC家族史的个体。我们建议在INHANCE Consortium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例病例和28，000例对照。我们的具体目标是：1）通过汇集有关职业暴露和口腔卫生的额外数据，对风险因素进行全面分析，并在INHANCE联盟中按地理区域估计其相应的归因风险; 2）为美国开发HNC和口腔癌、口咽癌、下咽癌和喉癌的第一个风险预测模型，使用aim 1结果和从SEER数据导出的基线癌症风险率;和3）验证来自队列联盟的美国队列中的HNC风险预测模型。竞争风险模型将用于估计在5年、10年和20年的时间间隔内发生这些癌症的概率。正在调查的风险因素包括吸烟、饮酒、HNC家族史、HPV感染、选择遗传变异、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到的癌症病例数以及使用队列联盟的队列数据的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力：1）在未来个性化医疗背景下的临床使用，2）牙医在决定是否进行口腔癌检查时超越传统的可视化检查，3）供有兴趣了解其HNC风险的个人公开使用（即，具有HNC家族史的个体），和4）用于研究，以选择高风险人群进行一级预防研究。另外，预测模型可以用作估计个体的风险降低的工具，以评估行为改变的影响（即，戒烟或减少饮酒）。INHANCE联盟中多学科研究人员的大规模合作为HNC的综合风险因素评估和风险预测模型项目提供了一个难得的机会。 公共卫生相关性：我们关于开发头颈癌风险预测模型的项目对公共卫生非常重要，因为它将作为一种工具来预测不同年龄组和风险因素组合的头颈癌绝对风险。该项目将是第一个评估世界各地区头颈癌风险因素综合清单的归因风险的项目（北美、拉丁美洲、欧洲和东亚），利用国际头颈癌联盟的大量汇总数据，建立美国口腔、口咽、下咽和喉的风险预测模型，并在队列联盟内的美国队列中验证风险预测模型。头颈癌风险预测对于促进临床和干预环境中的个性化医疗保健至关重要，以降低头颈癌发病率并提高生存率。

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. PUBLIC HEALTH RELEVANCE: Our project on the development of head and neck cancer risk prediction model is important for public health because it will contribute as a tool to predict the absolute risk of head and neck cancer across various age groups and risk factor profiles. This project will be the first of its kind to estimate the attributable risks of a comprehensive list of head and neck cancer risk factors across world regions (North America, Latin America, Europe, and East Asia), to utilize a large pooled data in the international head and neck cancer consortium for risk prediction model for oral cavity, oropharynx, hypopharynx, and larynx in the US, and to validate the risk prediction model in the US cohorts within the Cohort Consortium. Head and neck cancer risk prediction is essential to facilitate personalized health care in clinical and intervention settings in order to reduce head and neck cancer incidence and to improve survival.