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.

概括 该申请是为了响应特殊利益通知（NOSI）而提交 23-038。 所有性活跃的男性和男性在L终生中都被感染。 非洲（SSA），由于缺乏HPV疫苗接种，主要是HR-HPV菌株。 菌株，占大多数宫颈癌（〜99％）和口服和口交癌（鳞状细胞的85-96％） 多样性）。 高收入国家（HIC）（例如美国）等癌症筛查计划以及高流行率 HIV/AIDS。 疾病（OPMD），与宫颈癌不同的口服和口服癌的癌症阶段 （CC）没有发达的 （HIC），例如美国的表观遗传变化是癌症的标志，表观遗传学家代表 具有未开发的潜力，可以识别有计划暴露致癌物的妇女，例如 HRHPV感染，以预防效果，并最终引起侵入性癌症。 与宫颈癌相比，针对口腔癌女性的策略。 正在进行的R01授予的优势“口服HPV和相关口服/口咽癌的表观遗传学 在尼日利亚感染艾滋病毒的人”（EPOOCH）研究，以确定可能也有可能受到高潮风险的女性--- 同时（同步一致性）或neature（异步）在子宫颈中风险HPV。 一致性）。 两组妇女：口服HRHPV和宫颈HPV（n = 30，第1组），仅口服HRHPV（n = 30，第2组） 在口腔和口咽部位识别宫颈HRHPV相关的DNAM生物标志物 两个宫颈拭子中的表观遗传学特征 在父级R01项目R01CA27495201中； AIM 1中确定的基因特异性DNAM PCR技术。此验证将在伊巴丹大学进行 尼日利亚。 识别患有HRHPV感染的妇女，这些妇女将来可能会持续存在并发展为宫颈癌 研究补充剂将培训申请人，周日Oyellinde，MBBS，以获得新的技能和专业知识 分子流行病学项目的设计，表观基因组处理和分析，新测定开发， 道德且经济上合理的研究技术，以及为同行评审和赠款写作。