Project 3: Dynamics of Immune Signatures and Microbiome in Patients with Cervical Pre-Cancer and Cancer Among Women.

University Of Miami School Of Medicine, Coral Gables FL

Investigators

Abstract

Cervical cancer is the fourth most common cause of cancer among women worldwide and the third leading cause of cancer death among women in low-resource settings. In the United States (US), it is the third most common gynecologic malignancy, with an estimated 13,820 new diagnoses and 4,360 estimated deaths in 2024. Despite a decline in incidence in the US, Black and Hispanic women continue to have a disproportionate burden of disease and worse outcomes. Persistent infection with various strains of human papillomavirus (HPV) is responsible for most cervical cancer cases. Our supporting data show that subpopulations of US-born Black and Afro-Caribbean women have a higher risk of aggressive cervical cancer and are diagnosed at later stages of disease relative to White women. Unfortunately, limited biomarkers exist to detect cervical dysplasia prior to progressing to cancer that disproportionately affects certain women populations. Emerging evidence has shown that the microbiome contributes remarkably to human health, and it has been linked to immune function, inflammation, and cancer. HPV infection and related cancers may be uniquely affected by the microbiome since these cancers arise in the cervical mucosa, which has a distinctive and rich microbial environment. Among Black and Hispanic women, a non-lactobacillus predominance of the vaginal microbiome is more common, which is linked with a bacterial imbalance or inflammation. It was hypothesized that immune adaptations suited to ancestral environments may influence cancer risk in different populations, implying that the differences in adaptive and innate immune surveillance could be a key player in cancer’s different outcomes and that microbial-derived metabolites regulate immune and inflammatory responses. A deeper understanding of such mechanisms may have a positive impact on developing more effective personalized cancer immunotherapy. Due to persistent differences in cervical cancer prevalence among Black and Hispanic women, it is vital to investigate the mechanisms underlying these differences by dissecting study of circulating immune cells, inflammatory responses, and their association with the microbiome and metabolome in the tumor tissue microenvironment. Thus, we propose this novel and important study to investigate the role of the cervical microbiome and metabolome in regulating the immune response and inflammatory milieu among women (Hispanics, US-born Blacks, and Caribbean Born Blacks). We hypothesize that the microbiome and metabolome promote environmental cues that drive shifts in immune cells and immunological signatures as the disease progresses, and that there are differences by ancestry. Together, the study will help identify associations between the cervical microbiome, metabolome, immune mediators, and inflammation in different population groups. Findings will allow us to identify unique host immune and microbial signatures associated with cervical carcinogenesis, leading to development of precision medicine and prevention that can ultimately impact cancer outcomes in populations that have been disproportionally affected by CC.