This K43 application seeks to advance the research and career training of Dr. Jonah Musa, an Associate professor in obstetrics and gynecology at the University of Jos, Nigeria. Dr. Musa?s career goal is focused on improving cervical cancer outcomes through prevention and early detection and treatment of precancerous conditions of the cervix. The focus on prevention and early detection is novel in Nigeria and other Low and Middle-Income Countries (LMICs) where organized cervical cancer screening services are lacking with the consequence of high incidence and mortality due to late diagnosis. In Nigeria, over 53 million women are at risk of developing cervical cancer, and available cervical cancer screening coverage is less than 9% of the population at risk. The title of this proposed research, ?Vaginal Microbiome Associated with Cervical Intraepithelial Neoplasia and Cancer?, seeks to identify the microbiome community state types, inflammatory biomarkers and epigenetic markers in cervical intraepithelial neoplasia (CIN) and in invasive cervical cancer (ICC). In addition, we will study the longitudinal changes in these biomarkers during progression from low grades CIN to high grades CIN and ICC over time. This project is of great significance since the viruses attributed to ICC are commonly acquired through high-risk sexual behavior, and our understanding of the biomarkers associated with the HR-HPV found in high grades precancerous stages of the cervix and ICC could provide evidence for developing modifiable behavioral and therapeutic interventions for improved cervical cancer outcomes at the population levels, and also translate findings to development of early diagnostic markers for identifying women with high grades CIN in our screening population. Candidate?s background: I?m specialty trained in general obstetrics and gynecology in Nigeria, and have completed graduate level training and earned a Master of Science and Doctor of Philosophy degrees at Northwestern University. Currently working as co-investigator on an ongoing U54 NCI funded epigenetics of cervical cancer project in Jos Nigeria. Therefore, my short-term goal for this K43 is to acquire further theoretical and more importantly, experiential skills to be able to conduct microbiome research and apply quantitative methodology in understanding microbiome and molecular data more broadly, to contribute to the understanding of cervical cancer prevention in Nigeria and globally. In the long-term, I want to generate sufficient pilot data in this field of research that will enable me to successfully compete for an R01 funding and gain research independence from my team of mentors. Research: This proposal has 3 inter-related aims:
Aim 1 : Characterize vaginal microbiome and inflammatory biomarkers in the spectrum of cervical precancer and invasive cervical cancer;
Aim 2 : Determine longitudinal changes in vaginal microbiome and inflammatory biomarkers in women with low- grade CIN progressing to high-grades CIN and cancer over time;
Aim 3 : Determine epidemiologic predictors of microbiome, inflammatory and epigenetic biomarkers associated with high-grades CIN and ICC.
In absolute numbers, Nigeria is one of the countries with the highest burden and mortality due to invasive cervical cancer with over 53 million women at risk, and available cervical cancer screening by conventional cervical cytology coverage is less than 9%, partly responsible for over 14,000 new invasive cervical cancer cases and over 8,000 deaths every year. We know that the causative agent of this preventable cancer is a sexually transmissible virus, the high-risk human papillomavirus (HR-HPV) whose persistence leads to cellular transformations progressing to invasive cancer if not detected and treated. Since these viruses are acquired through high-risk sexual behavior, understanding the microbiome community state types, and the inflammatory biomarkers and epigenetic signatures associated with the HR-HPV in high grades precancerous stages of the cervix and ICC could provide evidence for developing primary interventions and early diagnostic markers for identifying these women in our population.