Investigation of Oral HPV Infection Natural History and Biomarkers of Persistent Infection: The HIM Study

口腔 HPV 感染自然史和持续感染生物标志物的调查：HIM 研究

• 批准号: 9883760
• 负责人: Anna R. Giuliano
• 金额: $ 71.34万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-21 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883760
• 关键词: Address; Adult; American Dental Association; Applications Grants; Archives; Behavioral; Biological; Biological Markers; Biological Specimen Banks; Cancer Control; Cancer Prevention Intervention; Cancerous; Cells; Centers for Disease Control and Prevention (U.S.); Cervical; Cessation of life; Cohort Studies; Consensus; Cytopathology; Data; Dental Hygiene; Development; Diagnosis; Early Diagnosis; Epidemiologist; Expenditure; Female; Funding; Future; Genital system; Goals; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Incidence; Infection; Infrastructure; Integration Host Factors; Interobserver Variability; Intervention; Investigation; Knowledge; Lesion; Life; Literature; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Medical; Methods; Methylation; Modality; Molecular; Natural History; Nested Case-Control Study; Non-Invasive Cancer Detection; Oncogenic; Oncologist; Operative Surgical Procedures; Oral; Oral health; Pain; Patients; Population; Predictive Factor; President' s Cancer Panel; Prevention; Prevention strategy; Preventive Intervention; Prospective Studies; Prospective cohort; Publishing; Quality of life; Recurrence; Research; Resources; Risk; Sampling; Screening for cancer; Screening procedure; Sex Behavior; Specimen; Surrogate Endpoint; Technology; Testing; Time; Tobacco use; Tooth Loss; Treatment outcome; Variant; Viral; Virus Integration; Woman; burden of illness; cancer diagnosis; cancer prevention; cancer risk; carcinogenicity; cervical and anal cancer; cervical cancer prevention; chemoradiation; chronic infection; clinically relevant; cohort; cost; design; disability; experience; follow-up; improved; innovation; male; malignant oropharynx neoplasm; men; mortality risk; novel; oral HPV; oral HPV infection; premalignant; productivity loss; progression marker; prospective; screening

ABSTRACT In 2013, 42,440 adults in the U.S. were diagnosed with oropharyngeal cancer (OPC), the majority at late stages, with an estimated five-year survival of 50% and a high rate of recurrence. Among those who survive, surgery and chemoradiotherapy leave patients with long-term pain, disfigurement, and disability that further add to the burden of the disease. Each year, OPCs are responsible for ~10,000 deaths, 130,000 years of potential life lost, and ~$3 billion in productivity loss. Earlier OPC diagnoses increase likelihood of single- modality treatment, lower the risk of mortality, decrease medical expenditures, and improve quality of life. HPV causes ~70% of OPCs in the US, with the proportion of OPCs due to HPV increasing each year. Incidence rates of HPV-related OPCs are also ~3-fold higher in males compared to females. While there is substantial literature regarding the natural history of genital HPV infection and progression to cervical cancer, little has been published on the natural history of oral HPV infection, thus limiting the development of OPC prevention interventions. Unlike cervical and anal cancers, no screening tests are available for OPC, nor have current HPV vaccines been evaluated for efficacy against these cancers. Therefore, in this grant application we propose to study oral HPV natural history through an established prospective cohort of average risk men, information urgently needed to inform the development of future prevention strategies, including clinically relevant screening tools. The HIM Study is the only male prospective study that has the cohort infrastructure and archived oral specimens to fill this critical research void. The overall goal of this research is to define the natural history of oral HPV infection to inform future development of OPC prevention and screening interventions. The central hypothesis is that viral, host, and behavioral factors are predictive of oral HPV infections that are most likely to persist ≥12 months (surrogate cancer endpoint), infections most likely to progress to cancer. We will estimate incidence and duration of oral HPV infections and associated factors. Novel viral (viral methylation, integration, variants), host (methylation), and behavioral (tobacco use, oral hygiene and health, sexual behavior,) factors will be evaluated in relation to oral HPV natural history. The proposed research is innovative, as it will be the first to prospectively address fundamental questions related to oral HPV natural history. Our study builds on an existing large data and biological specimen repository to efficiently address timely and significant questions identifying markers of infection that have utility for the design of future HPV-OPC screening/prevention interventions. Our transdisciplinary team of epidemiologists, biostatisticians, oncologists, and virologists has the experience and expertise to successfully implement the proposed study.

抽象的 2013年，美国有42,440名成年人被诊断出患有口咽癌（OPC），大多数人迟到 阶段，估计五年生存率为50％，复发率高。在那些生存的人中 手术和化学放疗使患者长期疼痛，毁容和残疾，进一步 加上疾病的燃烧。每年，OPC造成约10,000人死亡，130，000年 潜在的生命损失，生产率损失约为30亿美元。较早的OPC诊断增加了单一的可能性 模态治疗，降低死亡率的风险，降低医疗支出并改善生活质量。 HPV在美国导致约70％的OPC，而每年HPV造成的OPC比例增加。 与女性相比，男性的HPV相关OPC的发病率也高约3倍。而有 关于生殖器HPV感染和宫颈癌发展的自然史的大量文献， 关于口服HPV感染的自然史几乎没有发表，因此限制了OPC的发展 预防干预措施。与宫颈癌和肛门癌不同，OPC没有筛查测试，也没有 评估当前的HPV疫苗针对这些癌症的效率。因此，在此赠款申请中我们 通过既定的普通风险男人的前瞻性队列研究口腔HPV自然历史的提议， 迫切需要信息来告知未来预防策略的制定，包括临床 相关筛选工具。 HIM研究是唯一具有队列基​​础设施的男性前瞻性研究 并存档口头标本以填补这一关键研究空隙。 这项研究的总体目标是定义口服HPV感染的自然历史，以告知未来 开发OPC预防和筛查干预措施。中心假设是病毒，宿主和 行为因素可以预测口服HPV感染，最有可能持续≥12个月（替代 癌症终点），最有可能发展为癌症的感染。我们将估计口头事件和持续时间 HPV感染和相关因素。新型病毒（病毒甲基化，整合，变体），宿主（甲基化）， 以及将评估行为（烟草使用，口腔卫生和健康，性行为）的因素 口腔HPV自然史。拟议的研究具有创新性，因为它将是第一个前瞻性地解决的 与口腔HPV自然史有关的基本问题。我们的研究以现有的大数据为基础 生物标本存储库有效地解决及时且重大的问题，以确定 具有未来HPV-OPC筛查/预防干预措施的效用的感染。我们的 流行病学家，生物统计学家，肿瘤学家和病毒学家的跨学科团队具有经验和 成功实施拟议的研究的专业知识。