Understanding the impact of sexually transmitted infections and vaginal microbiome imbalance on cervical cancer development in mali: implications for new prevention strategies - human papillomavirus…

Understanding the impact of sexually transmitted infections and vaginal microbiome imbalance on cervical cancer development in mali: implications for new prevention strategies - human papillomavirus (HPV) is indeed the most common sexually transmitted infection (stis) in the united states (U.S.), with the vast majority of sexually active people contracting at least one type of HPV in their lifetime. In sub- saharan africa (SSA), nearly all women living with HIV who develop cervical cancer (CC) are CO-infected with HPV (~99%) and CC remains one of the leading causes of cancer-related deaths among women, where the burden is disproportionately high (~60% of all CC cases occur in this region), yet few of the eligible women are screened despite free services. This makes mali (a country in SSA) a valuable setting for conducting such research and for applying lessons learned to benefit U.S. And global health. While most HPV infections (80%-90%) are naturally cleared by the host immune system, persistent infection with high-risk HPV (hrhpv) types markedly increases the risk of oncogenic progression, ultimately leading to invasive CC. This progression unfolds over several years, providing a long window for preventive measures. Currently, there are no approved treatments to directly eliminate HPV infection, underscoring the importance of addressing and mitigating the factors (e.g., CO-infection with other stis) that promote HPV persistence as a key strategy for CC prevention and control. Recent studies highly suggest that CO-infection with other stis (CO-stis) may facilitate HPV persistence and accelerate the progression to CC. These findings highlight a crucial opportunity to design, test, and implement integrated dual-screening approaches that detect and address both HPV and CO-stis with appropriate treatments, as a strategy to prevent persistence of HPV and ultimately, CC. A balanced microbiome, usually dominated by lactobacillus species, helps sustain a protective acidic environment that inhibits the growth of pathogenic microorganisms and reduces the risk of stis. Its imbalance has been associated with increased susceptibility to stis and a greater likelihood of persistent HPV infections. For this K43, we seek to conduct a longitudinal cohort study, which will include both HIV and non-HIV women, using clinical data, self-sampled microbiology diagnostics, and metagenomic analysis to determine the role of CO-stis and vaginal microbiome in HPV persistence and cervical carcinogenesis. We will also develop a predictive framework to guide dual-screening strategies, predictive tools, and targeted preventive interventions tailored to CC control. This research program overall addresses an important epidemiological GAP by advancing our understanding of how CO-occurring stis and vaginal microbiome imbalance contribute to hrhpv persistence and cervical carcinogenesis, which will benefit women in low-resource settings in mali, U.S., and worldwide.