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

用于预测口咽癌复发的人乳头瘤病毒特异性生物标志物

• 批准号: 10285036
• 负责人: Krystle A. Kuhs
• 金额: $ 12.87万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-16 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285036
• 关键词: Active Learning; Address; Adoption; Aftercare; Antibodies; Basic Science; Biological Markers; Biometry; Cancer Patient; Cancer Survivorship; Cervical; Clinical; Clinical Data; Clinical Management; Clinical Trials; Collection; Data; Databases; Development; Diagnosis; Disease Management; Electronic Health Record; Enrollment; Epidemic; Epidemiology; Funding; Genome; Genomics; Goals; Head and Neck Cancer; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune response; Immunology; Incidence; Infection; Infrastructure; Institutional Review Boards; Joints; K-Series Research Career Programs; Knowledge; Lead; Mentors; Mentorship; Modality; Molecular; Molecular Epidemiology; Morbidity - disease rate; Oncogenes; Oncogenic; Oncoproteins; Operative Surgical Procedures; Oral; Outcome; Pathology; Patient Care; Patient-Focused Outcomes; Patients; Positioning Attribute; Prevention; Protocols documentation; Recurrence; Reporting; Research; Resource Sharing; Risk; Sampling; Secondary Prevention; Serum; Specimen; Survival Rate; Techniques; Tissues; Training; Treatment Protocols; Up-Regulation; Vaccinated; Variant; Viral; base; biobank; biomarker development; biomedical informatics; blood treatment; cancer prevention; cancer recurrence; cancer risk; carcinogenicity; career; clinical epidemiology; cohort; cytokine; design; experience; head and neck cancer patient; head and neck cancer prevention; high risk; improved; improved outcome; malignant oropharynx neoplasm; middle age; molecular marker; next generation sequencing; novel; novel marker; outcome forecast; patient population; personalized medicine; preservation; programs; prospective; risk prediction model; risk stratification; sample collection; seropositive; skills; specific biomarkers; tertiary prevention; treatment response; treatment risk; tumor; tumor immunology; uptake

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.

项目总结 该职业发展奖(CDA)旨在为Krystle A.Lang kuhs博士提供必要的技能和 导师计划开发一个专注于头颈部癌症预防的独立研究计划。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)检测头颈部癌症 早期(二级预防)；b)改进治疗前风险分层，根据预后进行个性化治疗 (三级预防)和；c)当高度治愈的抢救手术仍然是一种选择时，更早发现复发(第四级 预防)。这是郎古博士职业生涯中自然而然的下一步，因为它建立在她在癌症中的力量之上。 预防、基础科学、流行病学、致癌感染和生物标记物开发。然而，要实现她的目标 为了实现职业目标，Lang kuhs博士需要解决她培训中的三个主要差距：1)临床流行病学(患者群体 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)；以及3) 高级生物统计学(风险预测建模)。这种培训将通过课程作业、研讨会、体验式 学习、动手培训和指导。郎库斯博士将由分子流行病学领域的顶尖专家指导 和队列发育(魏征博士)、头颈癌免疫学(金英英博士)和头颈癌 生存(芭芭拉·墨菲博士)CDA的研究部分将集中在人类乳头瘤病毒驱动的 口咽癌(HPV-OPC)是一种增长迅速的头颈癌。而HPV-OPC的治疗通常是 治愈，它与严重的发病率有关。临床试验正在进行中，以调查是否降级 治疗HPV-OPC可以在保持高存活率的同时降低发病率。然而，最重要的是 采用降级治疗的障碍是无法识别复发风险最高的患者。这个 这项研究的目的是检验使用HPV特异性生物标记物来识别高危患者的潜在效用。 有复发的风险。这项研究将利用储存的生物标本和EHR数据来创建HPV-OPC的临床队列 患者要：1)检查OPC肿瘤内HPV病毒变异与复发之间的联系；2)检查 治疗前HPV16E6血清阳性和E6癌基因表达与复发风险的关系 制定和完善临床数据和来自OPC患者的生物标本的扩展预期收集方案。 从CDA获得的指导培训、实践经验和结果将使郎库博士成功地 争取资金建立一个独立的研究计划，专注于开发用于预防的生物标记物 头部和颈部癌症。