Predictors of HPV16 Status and Outcomes of Oropharyngeal Cancer Patients

描述（由申请人提供）：我的职业目标是发展积极的基于人群的癌症研究计划，对病毒相关癌症的分子和病毒流行病学。这一目标建立在我以前在包括生物科学在内的几个学科的培训基础上，但需要在流行病学方法学，病毒学和免疫学方面进行进一步的培训。在这个培训期结束时，我将成为一名独立的癌症预防研究人员。我制定了一个全面的教育和指导计划。我的教育计划将提供流行病学、病毒学和免疫学方面的强化教学。我已经选择了五位导师，两位顾问和两位合作者，他们将监督我培训的特定部分。我的研究计划将集中于确定口腔鳞状细胞癌（SCCOP）患者中HPV 16状态和HPV 16相关结局的易感性标志物。我建议利用两个目前正在进行的NIH资助的头颈癌病例对照研究和SCCOP外周血HPV 16 DNA随访研究进行病例-病例比较研究。我的研究目标是确定某些性行为和遗传多态性的细胞周期控制/细胞凋亡和炎症/免疫反应途径，可以作为HPV 16状态的风险预测和修改HPV 16相关的生存SCCOP患者。具体目标是：1）在300例SCCOP患者中调查某些性行为是否与HPV 16 * 状态风险增加相关。性行为和HPV 16状态之间的联系的影响将有助于确定SCCOP中与HPV 16相关的环境暴露，这具有明显的公共卫生影响，特别是考虑到最近批准HPV疫苗接种以预防宫颈癌; 2）研究细胞周期控制/凋亡和炎症/免疫反应途径中的不良基因型是否与HPV 16风险增加相关 * SCCOP患者中的状态。这些途径中涉及的遗传多态性可能在HPV 16感染易感性的人与人之间的差异中起重要作用，具有癌症预防意义;和3）确定细胞周期控制/凋亡和炎症/免疫应答途径中基因的选定常见遗传变异是否会改变HPV 16 * SCCOP患者的临床结局。虽然了解SCCOP患者的HPV 16状态可能会成为一个重要的预后意义，对未来的治疗和预防策略有潜在的影响，以提高生存率和生活质量，但了解与HPV 16阳性相关的结局的生殖系修饰将是实现更个性化，更少病态和更成功的癌症治疗目标的下一步。

DESCRIPTION (provided by applicant): My career goal is to develop active population-based cancer research programs on molecular and viral epidemiology of virus-associated cancers. This goal builds upon my previous training in several disciplines including biological sciences, but requires further training in epidemiologic methodology, virology, and immunology. At the end of this training period, I will be an established and independent researcher in cancer prevention. I have developed a comprehensive education and mentoring plan. My education plan will provide intensive instruction in the areas of epidemiology, virology, and immunology. I have chosen five mentors, two consultants and two collaborators who will supervise specific portions of my training. My research proposal will focus on identifying susceptibility markers for both HPV16 status and HPV16- associated outcome among squamous cell carcinoma of the oropharyx (SCCOP) patients. I propose a case-case comparison study capitalizing on two currently ongoing NIH-funded case-control study of head and neck cancer and HPV16 DNA in peripheral blood follow-up study of SCCOP. My research goal is to identify certain sexual behaviors and genetic polymorphisms in cell cycle control/apoptosis and inflammation/immune response pathways that could serve as predictors of risk of HPV16 status and modify HPV16-associated survival in SCCOP patients. The specific aims are: 1) To investigate if certain sexual behaviors are associated with an increased risk of HPV16* status among 300 incident SCCOP patients. The impact of a link between sexual behaviors and HPV16 status will help establish the environmental exposures associated with HPV16 in SCCOP, which has obvious public health implications especially in light of the recent approval of HPV vaccination to prevent cervical cancer; 2) To investigate if adverse genotypes in cell cycle control/apoptosis and inflammation/immune response pathways are associated with an increased risk of HPV16* status among SCCOP patients. Genetic polymorphisms involved in these pathways may play a significant role in person-to-person variability in susceptibility to HPV16 infection, having cancer prevention implications; and 3) To determine if selected common genetic variants of genes in cell cycle control/apoptosis and inflammation/immune response pathways modify clinical outcomes in patients with HPV16* SCCOP. While knowing the HPV16 status of SCCOP patients will likely become an important prognostic implication with potential influences on future treatment and prevention strategies for an improved survival and a better quality of life, understanding germline modifications of the outcomes associated with HPV16 positivity will be the next step toward the goal of more individualized, less morbid, and more successful cancer treatment.