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: 10705727
• 负责人: Lifang Hou
• 金额: $ 82.55万
• 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/10705727
• 关键词: Africa; Africa South of the Sahara; Age; Area; Benign; Biological Assay; Biology; Biopsy; Biopsy Specimen; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Patient; Cell Count; Chronic; Clinical; Code; Collaborations; Country; Cytology; DNA; DNA Methylation; DNA methylation profiling; Data; Development; Diagnosis; Disease; Epidemiology; Epigenetic Process; Europe; 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; Literature; 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; Predisposition; Prevalence; Prevention; Preventive; Public Health; Radiation Oncology; Research; Resources; Risk; Risk Factors; Role; Sampling; Satellite Hospitals; Screening for Oral Cancer; Screening for cancer; Sex Behavior; Site; Swab; Testing; Tissues; United States; Universities; Viral; Viral Load result; Virus; Virus Diseases; antiretroviral therapy; 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; oncology service; oral HPV; predictive marker; premalignant; prognostic; progression risk; 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.

项目概要/摘要 该项目的长期目标是 a) 了解人乳头瘤病毒 (HPV) 的流行病学 - HIV 感染者 (PLWH) 中相关的口腔癌和口咽癌 (OOPC) 以及 OOPC 中的表观遗传生物标志物，以及 b) 开发潜在的有针对性的干预措施，以改善预防和 OOPC 的早期检测。 HPV 导致全球约 5% 的癌症，其中 OOPC 的比例不断增加； 我们最近的数据显示，17% 的 OOPC 样本有 HPV 感染。这一日益恶化的公共卫生问题 在艾滋病毒感染率高的国家，例如尼日利亚，情况更为严重。 HIV感染对身体的影响 免疫功能障碍会促进致癌 HPV 合并感染的传播和重新激活。 HIV-HPV 共 感染会协同增加口腔潜在恶性疾病 (OPMD) 的患病率，并且 PLWH 中进展为 OOPC 的危险。由于艾滋病毒可通过抗逆转录病毒治疗 (ART) 得到控制，因此 PLWH 患有慢性炎症和持续免疫缺陷的人寿命更长，这使他们更容易受到感染 HPV 感染及其致癌后果。表观遗传生物标志物代表了一个尚未开发的领域 识别有进展为侵袭性 OOPC 风险的 HPV 感染 PLWH 的潜力。 DNA甲基化 (DNAm) 修饰是癌症（包括 OOPC）中经过充分研究的表观遗传机制。 DNAm修饰 是由外源因素诱导的，包括 HIV 和 HPV 感染及其相关癌症。国家 像尼日利亚这样的国家提供了独特的资源和机会来研究 PLWH 中的 HPV 相关癌症，特别是 OPMD 发展为恶性 OOPC 的纵向研究。我们假设口腔 HPV 感染 可能会诱导 PLWH 中的 DNAm 变化，其中一些是 OOPC 发展的机制。这样的改变 可能因 HPV 亚型而异，并且可以在预测进展为侵袭性 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) HPV(+) 伴有良性疣 (n=100)，4) HPV(+) 伴有 OPMD (n=400)。招聘 将在伊巴丹大学医学院/大学学院医院 (COMUI/UCH) 进行 尼日利亚、西非以及其他 10 个医院卫星招聘站点。 COMUI/UCH辐射最大 尼日利亚的肿瘤转诊网站，也是该地区领先的肿瘤服务中心之一。我们也会 研究来自同一地区现有队列 (SHINI) 的 HIV (-) OOPC 患者。我们的主要目标是 目的： 1) 了解 PLWH 中 HPV 相关 OOPC 的流行病学； 2) 鉴定 HPV 的 DNAm 生物标志物 PLWH 中相关的 OOPC； 3) 检查 DNAm 生物标志物的 OOPC 攻击性和 OPMD 随访期间的进展。我们的研究团队拥有长期成功的合作记录， 西北大学 MPI 在研究 PLWH 中 HPV 相关宫颈癌方面拥有丰富的经验 通过 NCI 资助的尼日利亚 U54 财团。