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活跃的基于人群的癌症研究项目，研究病毒相关癌症的分子和病毒流行病学。这个目标建立在我之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论、病毒学和免疫学方面进行进一步的培训。在这次培训结束后，我将成为癌症预防方面的一名成熟的独立研究人员。我已经制定了一个全面的教育和指导计划。我的教育计划将在流行病学、病毒学和免疫学领域提供密集的指导。我选择了五名导师、两名顾问和两名合作者，他们将监督我培训的具体部分。我的研究计划将集中于确定口咽鳞状细胞癌(SCCOP)患者中HPV16状态和HPV16相关结局的易感标志物。我提出了一项病例-病例对照研究，该研究利用了目前正在进行的两项由美国国立卫生研究院资助的头颈癌病例对照研究和SCCOP患者外周血中HPV16DNA的随访研究。我的研究目标是确定细胞周期控制/凋亡和炎症/免疫反应途径中的某些性行为和基因多态性，这些行为和基因多态性可以预测HPV16状态的风险，并改变SCCOP患者的HPV16相关生存。具体目标是：1)在300名SCCOP患者中，调查某些性行为是否与HPV16*状态的风险增加有关。性行为与HPV16状态之间的联系的影响将有助于确定SCCOP中与HPV16*状态相关的环境暴露，这具有明显的公共卫生影响，特别是考虑到最近HPV疫苗被批准用于预防宫颈癌；2)调查细胞周期控制/细胞凋亡和炎症/免疫反应通路中的不利基因是否与SCCOP患者HPV16*状态的风险增加相关。这些途径中涉及的基因多态可能在人与人之间的HPV16感染易感性中发挥重要作用，具有预防癌症的意义；以及3)确定细胞周期控制/凋亡和炎症/免疫反应途径中选定的常见基因变异是否会改变HPV16*SCCOP患者的临床结果。虽然了解SCCOP患者的HPV16状态可能成为一项重要的预后意义，可能会对未来的治疗和预防策略产生潜在影响，以提高生存率和生活质量，但了解与HPV16阳性相关的预后的胚系修改将是朝着更个体化、更少病死率和更成功的癌症治疗目标迈出的下一步。

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.