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 名成年人被诊断患有口咽癌 (OPC)，其中大多数已处于晚期 期，预计五年生存率为 50%，且复发率很高。在那些幸存下来的人中， 手术和放化疗给患者带来长期疼痛、毁容和残疾，进一步加剧 加重疾病负担。每年，OPC 导致约 10,000 人死亡，130,000 年 潜在的生命损失和约 30 亿美元的生产力损失。早期 OPC 诊断会增加单发的可能性 方式治疗，降低死亡风险，减少医疗支出，提高生活质量。 在美国，约 70% 的 OPC 是由 HPV 引起的，并且由 HPV 引起的 OPC 的比例每年都在增加。 与女性相比，男性 HPV 相关 OPC 的发病率也高出约 3 倍。虽然有 关于生殖器 HPV 感染的自然史和宫颈癌进展的大量文献， 关于口腔 HPV 感染自然史的报道很少，从而限制了 OPC 的发展 预防干预措施。与宫颈癌和肛门癌不同，OPC 没有可用的筛查测试，也没有 目前的 HPV 疫苗针对这些癌症的功效已得到评估。因此，在本次拨款申请中，我们 提议通过已建立的平均风险男性前瞻性队列研究口腔 HPV 自然史， 迫切需要信息来为未来预防策略的制定提供信息，包括临床预防策略 相关筛选工具。 HIM 研究是唯一一项拥有队列基础设施的男性前瞻性研究 并存档口腔标本以填补这一重要的研究空白。 这项研究的总体目标是确定口腔 HPV 感染的自然史，为未来提供信息 制定 OPC 预防和筛查干预措施。中心假设是病毒、宿主和 行为因素可预测口腔 HPV 感染，最有可能持续 ≥12 个月（替代 癌症终点），感染最有可能进展为癌症。我们将估计口腔疾病的发生率和持续时间 HPV 感染及相关因素。新型病毒（病毒甲基化、整合、变异）、宿主（甲基化）、 行为（烟草使用、口腔卫生和健康、性行为）因素将根据以下方面进行评估 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解决 与口腔 HPV 自然史相关的基本问题。我们的研究建立在现有的大数据和 生物样本库，以有效解决及时和重要的问题，识别标记物 对设计未来 HPV-OPC 筛查/预防干预措施具有实用性。我们的 由流行病学家、生物统计学家、肿瘤学家和病毒学家组成的跨学科团队拥有丰富的经验和 成功实施拟议研究的专业知识。