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.

摘要