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

点击翻译按钮获取中文摘要

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.