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.

项目总结/文摘