Epigenetic biomarkers of Cervical HPV in women with oral and oropharyngeal HPV, precancer and cancer

患有口腔和口咽 HPV、癌前病变和癌症的女性中宫颈 HPV 的表观遗传生物标志物

• 批准号: 10841283
• 负责人: Lifang Hou
• 金额: $ 12.5万
• 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/10841283
• 关键词: Africa South of the Sahara; Anatomy; Biological; Biological Markers; Carcinogens; Cervical; Cervical Cancer Screening; Cervix Uteri; Collection; Country; Cytology; DNA; DNA Methylation; Data; Data Analyses; Detection; Development; Disease; Enrollment; Epigenetic Process; Ethics; Exposure to; Fingers; Future; Genes; Genotype; Goals; Grant; HIV; HIV/AIDS; HPV-High Risk; Hand; High Prevalence; Human Papilloma Virus Vaccination; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Human papillomavirus 18; Income; Infection; Laboratories; Lead; Learning; Link; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Manuals; Manuscripts; Masturbation; Mentors; Methylation; Molecular Epidemiology; Nigeria; Oral; Oral Examination; Oral Stage; Oropharyngeal; Parents; Participant; Peer Review; Persons; Population; Progress Reports; Protocols documentation; Recording of previous events; Research; Research Design; Research Technics; Risk; Sampling; Sex Behavior; Sexually Transmitted Diseases; Site; Squamous Cell; Supervision; Swab; Technology; Testing; Time; Training; United States National Institutes of Health; Universities; Vagina; Validation; Woman; Women' s Group; Work; Writing; assay development; cancer biomarkers; cancer invasiveness; computerized data processing; epigenetic marker; epigenetic profiling; epigenomics; ethical, legal, and social implication; high risk; interest; malignant mouth neoplasm; malignant oropharynx neoplasm; men; oral HPV; oral HPV infection; premalignant; progression risk; recruit; research study; response; screening; screening program; sexually active; skills; sound; tool

Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 23-038. Human Papillomavirus (HPV) is the most common sexually-transmitted infection worldwide, with nearly all sexually active women and men infected during their lifetime. HPV infection is highly prevalent in Sub-Saharan Africa (SSA), due to the lack of widespread HPV vaccination. Infection of hr-HPV strains, mainly HPV 16 and 18 strains, accounts for most cervical cancer (~99%) and oral and oropharyngeal cancer (85-96% of squamous cell variety). HPV associated cancers are rapidly increasing in SSA due to lack of HPV vaccination and cervical cancer screening programs like high income countries (HICs), such as U.S., as well as high prevalence of HIV/AIDS. Infection with high-risk HPV (hr-HPV), mainly HPV 16 and 18, leads to oral potentially malignant disorders (OPMD), the precancerous stage of oral and oropharyngeal cancers (OOPCs). Unlike cervical cancer (CC) there are no well-developed, population-level screening programs for OOPC, even in high income countries (HICs) such as the U.S. Epigenetic changes are a hallmark of cancer, and epigenetic biomarkers represent a field with untapped potential for identifying women at risk of progression from exposure to carcinogens, such as hrHPV infection, to pre-malignancy, and ultimately to invasive cancers. Now, there is no universal screening strategy for women with oral or oropharyngeal cancer compared to cervical cancer. It is important to take advantage of the ongoing R01 grant “Epigenetics of oral HPV and associated oral/oropharyngeal cancer in people living with HIV in Nigeria” (EpOOCH) study to identify women that might also be at risk of having high- risk HPV in the cervix at the same time (synchronous concordance) or in the nearest future (asynchronous concordance). The aims of this project are: 1) To conduct cervical swab epigenetic profiling (at Northwestern) in two groups of women: oral hrHPV and cervical HPV (n=30, Group 1) vs. oral hrHPV only (n=30, Group 2) to identify cervical hrHPV-associated DNAm biomarkers also seen in oral and oropharyngeal sites. We will compare epigenetic profile in both cervical swab (will be profiled by this supplement) and oral swab (have been obtained in the parent R01 project R01CA27495201); and 2) To validate the hrHPV-associated biomarkers in cervix using gene-specific DNAm PCR technology identified in Aim 1. This validation will be performed at University of Ibadan, Nigeria. Our long-term goal for this mentored research is to develop biomarkers or tools that can screen or identify women with hrHPV infections that could persist and develop into cervical cancer in future. This mentored research Supplement will train the applicant, Sunday Oyerinde, MBBS, to gain new skills and expertise in study design of molecular epidemiology projects, epigenomic processing and analysis, new assay development, ethical and economically sound research techniques, and writing for peer review and grants.

总结 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 23-038.人乳头瘤病毒（HPV）是世界上最常见的性传播感染， 所有性行为活跃的男女在其一生中都受到感染。HPV感染在撒哈拉以南非洲地区非常普遍 非洲（SSA），由于缺乏广泛的HPV疫苗接种。hr-HPV毒株感染，主要是HPV 16和18 菌株，占大多数宫颈癌（约99%）和口腔和口咽癌（鳞状细胞癌的85- 96 品种）。由于缺乏HPV疫苗接种和宫颈癌， 癌症筛查计划，如高收入国家（HIC），如美国，以及高患病率 艾滋病毒/艾滋病的感染高危型HPV（hr-HPV），主要是HPV 16和18，导致口腔潜在恶性 口腔癌和口咽癌的癌前阶段（OOPC）。不像宫颈癌 (CC)即使在高收入国家，也没有完善的、人口水平的OOPC筛查计划 表观遗传学变化是癌症的标志，表观遗传学生物标志物代表了癌症的特征。 该领域在识别因接触致癌物而面临进展风险的女性方面具有尚未开发的潜力，例如 hrHPV感染，到癌前病变，并最终到浸润性癌症。现在，没有普遍的筛查 与宫颈癌相比，口腔癌或口咽癌女性的治疗策略。重要的是采取 正在进行的R 01资助的优势“口腔HPV和相关口腔/口咽癌的表观遗传学， 尼日利亚艾滋病毒感染者”（EpOOCH）的研究，以确定妇女也可能有高风险， 同时（同步一致性）或在最近的将来（异步）宫颈中的HPV风险 concordance）。该项目的目的是：1）在美国西北大学进行宫颈拭子表观遗传学分析， 两组女性：口服hrHPV和宫颈HPV（n=30，组1）与仅口服hrHPV（n=30，组2）， 鉴定在口腔和口咽部位也可见宫颈hrHPV相关DNAm生物标志物。我们将比较 宫颈拭子（将通过本补充材料进行分析）和口腔拭子（已获得）的表观遗传特征 在父R 01项目R 01 CA 27495201中）;和2）使用 目的1中确定的基因特异性DNAm PCR技术。本确认将在伊巴丹大学进行， 尼日利亚。我们这项指导研究的长期目标是开发生物标志物或工具， 识别hrHPV感染的妇女，这些感染可能持续存在并在未来发展为宫颈癌。这一指导 研究补充将培训申请人，星期日Oyerinde，MBBS，以获得新的技能和专业知识的研究 分子流行病学项目的设计，表观基因组处理和分析，新检测方法的开发， 道德和经济上合理的研究技术，并为同行评审和赠款写作。