Epigenetic study of oral HPV infection-associated oral cancer in people living with HIV in Nigeria

尼日利亚 HIV 感染者口腔 HPV 感染相关口腔癌的表观遗传学研究

• 批准号: 10530153
• 负责人: Lifang Hou
• 金额: $ 74.35万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530153
• 关键词: Africa; Africa South of the Sahara; Age; Area; Benign; Biological Assay; Biology; Biopsy; Biopsy Specimen; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; Cancer Patient; Cell Count; Chronic; Clinical; Code; Collaborations; Country; Cytology; DNA; DNA Methylation; DNA methylation profiling; Data; Development; Diagnosis; Disease; Epidemiology; Epigenetic Process; Exogenous Factors; Funding; Future; Gene Expression; Genotype; Goals; HIV; HIV Infections; HPV-High Risk; Health care facility; High Prevalence; Hospitals; Human Papillomavirus; Immune System Diseases; Immune system; Immunologic Deficiency Syndromes; Individual; Inflammation; Inherited; Intervention; Lesion; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Medicine; Modification; Mouthwash; Nigeria; Nigerian; Oncogenic; Oral; Oral Sex; Oral cavity; Outcome; Participant; Patients; Persons; Prevalence; Prevention; Preventive; Public Health; Radiation Oncology; Research; Resources; Risk; Risk Factors; Role; Sampling; Satellite Hospitals; Screening for Oral Cancer; Screening for cancer; Services; Sex Behavior; Site; Swab; Testing; Tissues; United States; Universities; Viral; Viral Load result; Virus; Virus Diseases; antiretroviral therapy; base; biomarker development; cancer biomarkers; co-infection; cohort; college; cost effective; early detection biomarkers; epigenetic marker; experience; follow-up; genome-wide; hazard; improved; malignant mouth neoplasm; malignant oropharynx neoplasm; methylation biomarker; novel strategies; oral HPV; predictive marker; premalignant; prognostic; prospective; recruit; screening; sex; specific biomarkers; therapeutic target; transmission process; trend; tumor; virus related cancer; young adult

PROJECT SUMMARY/ABSTRACT The long-term goals of this project are to a) understand the epidemiology of Human papillomavirus virus (HPV)- associated oral and oropharyngeal cancers (OOPC) among people living with HIV (PLWH) as well as the role of epigenetic biomarkers in OOPC, and b) to develop potential targeted interventions to improve prevention and early detection of OOPC. HPV causes ~5% of cancers worldwide, including an increasing proportion of OOPCs; our recent data showed that 17% of OOPC samples have HPV infections. This worsening public health problem is even more serious in countries with high HIV prevalence, such as Nigeria. The impact of HIV infection on immune dysfunction promotes transmission and reactivation of oncogenic HPV co-infections. HIV-HPV co- infection then synergistically increases the prevalence of oral potentially malignant disorders (OPMDs), and the hazards of progression to OOPC among PLWH. As HIV is controlled with antiretroviral therapy (ART), PLWH live longer with chronic inflammation and continued immunodeficiency, making them even more susceptible to HPV infection and its cancer-promoting consequences. Epigenetic biomarkers represent a field with untapped potential for identifying HPV-infected PLWH who are at risk of progression to invasive OOPC. DNA methylation (DNAm) modifications are a well-studied epigenetic mechanism in cancer including OOPC. DNAm modifications are inducible by exogenous factors, including HIV and HPV infection and their associated cancers. Countries like Nigeria provide unique resources and opportunities to study HPV-associated cancers in PLWH, particularly longitudinal studies of the progression of OPMDs into malignant OOPCs. We hypothesize that oral HPV infection may induce DNAm changes in PLWH, some of which are mechanisms in OOPC development. Such changes may differ by HPV subtype, and can be seen in OPMDs that predict the progression to invasive OOPC. We plan to examine tissue-specific epigenetic biomarkers in 4 groups of HIV(+) patients: 1) HPV(+) OOPC (n=150); 2) HPV(-) OOPC (n=150); 3) HPV(+) with benign warts (n=100), and 4) HPV(+) with OPMDs (n=400). Recruitment will be conducted at the College of Medicine, University of Ibadan/University College Hospital (COMUI/UCH) in Nigeria, West Africa as well as 10 other hospital satellite recruitment sites. COMUI/UCH is the largest radiation oncology referral site in Nigeria and one of the leading centers for oncological services in the region. We will also study HIV (-) OOPC patients derived from our existing cohort (SHINI) in the same area. Our primary Aims are to: 1) Understand the epidemiology of HPV-associated OOPCs in PLWH; 2) Identify DNAm biomarkers of HPV- associated OOPCs in PLWH; and 3) Examine DNAm biomarkers for OOPC aggressiveness and OPMD progression during follow up. Our research team has a long and successful collaboration record and the Northwestern University MPIs have extensive experience studying HPV-associated cervical cancer in PLWH through an NCI-funded U54 consortium in Nigeria.

项目摘要/摘要 该项目的长期目标是a）了解人类乳头瘤病毒病毒（HPV）的流行病学 - 患有艾滋病毒（PLWH）的患者的相关口腔和口腔咽部癌（OOPC）以及 OOPC中的表观遗传生物标志物，b）开发潜在的靶向干预措施，以改善预防和 早期检测到OOPC。 HPV在全球造成约5％的癌症，包括越来越多的OOPC； 我们最近的数据表明，17％的OOPC样品患有HPV感染。这加剧了公共卫生问题 在尼日利亚等艾滋病毒率高的国家中，更为严重。艾滋病毒感染对 免疫功能障碍促进致癌HPV共感染的传播和重新激活。 HIV-HPV共同 然后，感染协同增加了口服潜在恶性疾病（OPMD）的患病率，并增加 PLWH中向OOPC的进展危害。由于HIV受抗逆转录病毒疗法（ART）的控制，PLWH 慢性炎症和持续免疫缺陷寿命更长，使其更容易受到 HPV感染及其癌症的后果。表观遗传生物标志物代表一个未开发的领域 识别有进展为侵入性OOPC风险的HPV感染的PLWH的潜力。 DNA甲基化 （DNAM）修饰是包括OOPC在内的癌症中良好的表观遗传机制。 DNAM修改 由外源性因素诱导，包括HIV和HPV感染及其相关的癌症。国家 像尼日利亚一样，提供了独特的资源和机会来研究PLWH中与HPV相关的癌症，尤其是 OPMD进展为恶性OOPC的纵向研究。我们假设口服HPV感染 可能会诱导dnam的变化，其中一些是OOPC开发中的机制。这样的变化 HPV亚型可能会有所不同，并且可以在预测侵入性OOPC的OPMD中看到。我们计划 检查4组HIV（+）患者的组织特异性表观遗传生物标志物：1）HPV（+）OOPC（n = 150）； 2） HPV（ - ）OOPC（n = 150）; 3）良性疣（n = 100）和4）HPV（+）和OPMD（n = 400）的HPV（+）。招聘 将在伊巴丹大学/大学学院医院（COMUI/UCH）的医学院进行 尼日利亚，西非以及其他10个医院卫星招募地点。 COMUI/UCH是最大的辐射 尼日利亚的肿瘤学转介地点是该地区肿瘤学服务的主要中心之一。我们也会 研究HIV（ - ）OOPC患者来自同一地区现有队列（Shini）的患者。我们的主要目的是 TO：1）了解PLWH中与HPV相关的OOPC的流行病学； 2）识别HPV-的DNAM生物标志物 PLWH中的相关OOPC； 3）检查DNAM生物标志物的OOPC侵略性和OPMD 随访期间的进展。我们的研究团队拥有漫长而成功的协作记录， 西北大学MPI在PLWH中研究HPV相关的宫颈癌具有丰富的经验 通过尼日利亚的NCI资助的U54财团。