Human Papillomavirus-Specific Biomarkers for the Prediction of Oropharyngeal Cancer Recurrence

项目摘要 这个职业发展奖（CDA）的目的是提供博士Kampelle A。拥有必要技能的朗库， 导师开发一个独立的研究计划，重点是头部和颈部癌症的预防。她的目标 未来的研究计划是通过使用分子标记来改善患者的预后：a）检测头颈癌 早期（二级预防）; B）改善治疗前风险分层，以根据预后进行个性化治疗 （三级预防）和; c）当高治愈性挽救手术仍是一种选择时，早期检测复发（四级 预防）。这是朗·库博士职业生涯中自然的下一步，因为它建立在她在癌症方面的优势之上。 预防、基础科学、流行病学、致癌感染和生物标志物开发。然而，为了实现她 为了实现职业目标，Lang Kuhs博士需要解决她培训中的3个主要差距：1）临床流行病学（患者人群 经验和临床队列建设）; 2）生物医学信息学（使用电子健康记录[EHR]数据）;和3） 高级生物统计学（风险预测模型）。这种培训将通过课程，研讨会，体验 学习、实践培训和指导。Lang Kuhs博士将接受分子流行病学领域领先专家的指导 头颈癌免疫学（Young Kim博士）和头颈癌 芭芭拉·墨菲博士（Dr. Barbara Murphy）该CDA的研究部分将重点关注人乳头瘤病毒驱动的 口咽癌（HPV-OPC），一种快速增长的头颈癌。虽然HPV-OPC的治疗通常 治愈，它与严重的发病率。临床试验正在进行中，以调查是否降级 HPV-OPC的治疗可以降低发病率，同时仍然保持高的存活率。然而，最重要的 采用降级治疗的障碍是无法识别复发风险最高的患者。的 本研究的目的是检查使用HPV特异性生物标志物识别最高水平的患者的潜在效用。 复发的风险。这项研究将利用库存生物标本和EHR数据来创建HPV-OPC的临床队列 患者：1）检查OPC肿瘤内HPV病毒变异体与复发之间的关联; 2）检查 治疗前HPV 16 E6血清阳性与E6癌基因表达和复发风险之间的关联;以及3） 制定和完善扩大前瞻性收集OPC患者临床数据和生物标本的方案。 指导培训，实践经验和从CDA中获得的结果将使Lang Kuhs博士成功地 争取资金，建立一个独立的研究计划，重点是开发生物标志物， 头颈部癌症

PROJECT SUMMARY This Career Development Award (CDA) is designed to provide Dr. Krystle A. Lang Kuhs with the necessary skills and mentorship to develop an independent research program focused on head and neck cancer prevention. The goals of her future research program are to improve patient outcomes by using molecular markers to: a) detect head and neck cancers earlier (secondary prevention); b) improve pre-treatment risk stratification to personalize therapy based on prognosis (tertiary prevention) and; c) detect recurrences earlier when highly-curative salvage surgery is still an option (quaternary prevention). This is the natural next-step in Dr. Lang Kuhs’ career given that it builds upon her strengthens in cancer prevention, basic science, epidemiology, oncogenic infections, and biomarker development. However, to achieve her career goals, Dr. Lang Kuhs will need to address 3 main gaps in her training: 1) clinical epidemiology (patient population experience and clinical cohort building); 2) biomedical informatics (use of electronic health record [EHR] data); and 3) advanced biostatistics (risk prediction modeling). This training will be obtained through coursework, seminars, experiential learning, hands on training and mentorship. Dr. Lang Kuhs will be mentored by leading experts in molecular epidemiology and cohort development (Dr. Wei Zheng), head and neck cancer immunology (Dr. Young Kim) and head and neck cancer survivorship (Dr. Barbara Murphy). The research portion of this CDA will focus on human papillomavirus-driven oropharyngeal cancer (HPV-OPC), a type of rapidly increasing head and neck cancer. While treatment of HPV-OPC is often curative, it is associated with severe morbidity. Clinical trials are underway to investigate whether de-escalation of treatment for HPV-OPC can decrease morbidity while still preserving high survival rates. However, the most significant barrier for the adoption of de-escalated treatment is the inability to identify patients at highest risk for recurrence. The objective of this research is to examine the potential utility of using HPV-specific biomarkers to identify patients at highest risk for recurrence. This research will utilize banked biospecimens and EHR data to create a clinical cohort of HPV-OPC patients to: 1) examine the association between HPV viral variants within OPC tumors and recurrence; 2) examine the association between pre-treatment HPV16 E6 seropositivity and E6 oncogene expression and risk recurrence; and 3) develop and refine protocols for expanded prospective collection of clinical data and biospecimens from OPC patients. The mentored training, hands on experience and results gained from this CDA will position Dr. Lang Kuhs to successfully compete for funding to establish an independent research program focused on developing biomarkers for the prevention of head and neck cancer.