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: 9906763
• 负责人: Krystle A. Kuhs
• 金额: $ 1.97万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2020-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906763
• 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; Risk stratification; 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; 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.

项目摘要 该职业发展奖（CDA）旨在为Krystle A. Lang Kuhs提供必要的技能和 制定一项独立研究计划的遗产，重点是预防头颈癌。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）检测头癌 早期（二级预防）； b）改善基于预后的个性化治疗的预处理风险分层 （第三级预防）和； c）当仍然可以选择高度策略的救助手术时检测回报（第四纪） 预防）。这是Lang Kuhs博士职业生涯的自然下一步 预防，基础科学，流行病学，致癌感染和生物标志物发育。但是，要实现她 职业目标，Lang Kuhs博士将需要在培训中解决3个主要差距：1）临床流行病学（患者人群 经验和临床队列建筑）； 2）生物医学信息（使用电子健康记录[EHR]数据）； 3） 高级生物统计学（风险预测建模）。该培训将通过课程，半小伙子，经验丰富 学习，动手训练和心态。 Lang Kuhs博士将由分子流行病学领域的领先专家进行修复 和队列开发（Wei Zheng博士），头颈癌免疫学（Young Kim博士）和头颈癌 生存（芭芭拉·墨菲博士）。该CDA的研究部分将集中于人乳头瘤病毒驱动 口咽癌（HPV-OPC），一种快速增加的头部和颈部癌。而HPV-OPC的治疗通常是 治愈性，它与严重的发病率有关。正在进行临床试验以调查是否降级 HPV-OPC的治疗可以降低发病率，同时仍然保留高生存率。但是，最重要的 采用降级治疗的障碍是无法识别出最高风险复发的患者。 这项研究的目的是检查使用HPV特异性生物标志物鉴定患者最高的潜在效用 复发的风险。这项研究将利用银行的生物测量和EHR数据来创建HPV-OPC的临床队列 患者：1）检查OPC肿瘤内HPV病毒变异与复发之间的关联； 2）检查 治疗前HPV16 E6 Serapititive与E6致癌基因表达与风险复发之间的关联； 3） 开发和完善方案，以扩大OPC患者的前瞻性收集临床数据和生物测量。 受过指导的培训，手中的经验和从该CDA中获得的成绩将使Lang Kuhs博士成功地取得成功 竞争资金建立一个独立的研究计划，旨在为预防开发生物标志物 头颈癌。