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: 10115630
• 负责人: Anna R. Giuliano
• 金额: $ 71.18万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115630
• 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; Genitalia; 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; 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; biological specimen archives; burden of illness; cancer diagnosis; cancer prevention; cancer risk; carcinogenicity; cervical and anal cancer; cervical cancer prevention; chemoradiation; chronic infection; clinically relevant; cohort; cost; data archive; design; detection method; disability; efficacy evaluation; experience; follow-up; improved; innovation; male; malignant oropharynx neoplasm; men; mortality risk; novel; oral HPV; oral HPV infection; premalignant; preventive intervention; 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 2013年，美国有42，440名成年人被诊断出患有口咽癌（OPC），其中大多数是晚期患者。 分期，估计5年生存率为50%，复发率高。在幸存者中， 手术和放化疗给患者留下长期疼痛、毁容和残疾， 增加了疾病的负担。每年，OPCs造成约10，000人死亡，130，000年的死亡率。 潜在的生命损失，以及约30亿美元的生产力损失。早期的OPC诊断增加了单- 模式治疗，降低死亡风险，减少医疗费用，提高生活质量。 在美国，HPV导致约70%的OPCs，由于HPV导致的OPCs比例每年都在增加。 男性HPV相关OPCs的发病率也比女性高约3倍。虽然 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感染的自然史，几乎没有发表，因此限制了OPC的发展 预防干预。与宫颈癌和肛门癌不同，OPC没有筛查测试， 目前的HPV疫苗已被评估对这些癌症的功效。因此，在这份资助申请中，我们 建议通过一个已建立的平均风险男性前瞻性队列研究口腔HPV自然史， 迫切需要的信息，为制定未来的预防战略提供信息，包括临床 相关的筛选工具。HIM研究是唯一具有队列基础设施的男性前瞻性研究 和存档的口腔标本来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， 制定OPC预防和筛查干预措施。核心假设是病毒、宿主和 行为因素是口腔HPV感染的预测因素，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。我们将估计口服给药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、变体）、宿主（甲基化）， 和行为（烟草使用，口腔卫生和健康，性行为）因素将进行评估， 口腔HPV自然史拟议的研究是创新的，因为它将是第一个前瞻性地解决 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基础上， 生物标本库，以有效地解决及时和重大的问题， 感染，可用于设计未来的HPV-OPC筛查/预防干预。我们 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， 成功实施拟议研究的专业知识。

项目成果

Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study.

根据男性 HPV 感染研究，口腔中 Epstein-Barr 病毒 (EBV) 的控制与男性口腔人乳头瘤病毒 (HPV)16/18 的持续存在相关。

• DOI: 10.1093/infdis/jiac223
• 发表时间: 2023
• 期刊: The Journal of infectious diseases
• 作者: Dickey,BrittneyL;Giuliano,AnnaR;Sirak,Bradley;Abrahamsen,Martha;Lazcano-Ponce,Eduardo;Villa,LuisaL;Coghill,AnnaE
• 通讯作者: Coghill,AnnaE

Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome.

• DOI: 10.1371/journal.pone.0254161
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Dickey BL;Sirak B;Martin-Gomez L;Reich RR;Abrahamsen M;Isaacs-Soriano K;Chung CH;Giuliano AR
• 通讯作者: Giuliano AR

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

• DOI: 10.1002/ijc.33732
• 发表时间: 2021-10-01
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Dickey BL;Fan W;Bettampadi D;Reich RR;Sirak B;Abrahamsen M;Baggio ML;Galan L;Silva RC;Salmerón J;Villa LL;Lazcano-Ponce E;Giuliano AR
• 通讯作者: Giuliano AR

Differences in Factors Associated With High- and Low-Risk Oral Human Papillomavirus Genotypes in Men.

男性高风险和低风险口腔人乳头瘤病毒基因型相关因素的差异。

• DOI: 10.1093/infdis/jiaa693
• 发表时间: 2021
• 期刊: The Journal of infectious diseases
• 作者: Bettampadi,Deepti;Dickey,Brittney;Abrahamsen,Martha;Sirak,Bradley;Baggio,MariaLuiza;Galan,Lenice;Silva,RobertoCarvalho;Villa,Luisa;Ponce,EduardoLazcano;Giuliano,AnnaR
• 通讯作者: Giuliano,AnnaR