Molecular Signatures of Cervical Cancer Risk in the Context of HIV Infection: Potential biomarkers of immune activation

Abstract

Abstract The disparity in cervical cancer incidence and mortality between high-income and low-income countries, exacerbated by the co-occurrence of HIV infection and cervical cancer, presents a complex and distinctive healthcare challenge. Addressing this challenge necessitates a comprehensive investigation into intricate molecular markers for predicting heightened cancer risk. This study assessed the cellular levels of cervical cancer-related specific oncomirs (miR-21, miR-146a, miR-155, miR-182, and miR-200c) and tumour suppressors (miR-let-7b, miR-125b, miR-143, miR-145, and p53) among women living with HIV (HIV+) and those without HIV (HIV-). Methods: This case-control study was conducted from May 2017 to April 2019 in Abeokuta, Nigeria, and involved two groups: HIV+ (n = 103) and HIV- women (n = 70). Results: The study revealed significantly higher levels of miR-155 and p53 in HIV+ women compared to their HIV- counterparts (p = 0.046 and 0.033, respectively). Conversely, significantly lower levels of miR-182, miR-200c, and miR-125b were observed in HIV+ women compared to their HIV- counterparts (p= 0.035, 0.045 and 0.004, respectively). Notably, a significant positive correlation was observed between miR-155 and miR-145 in both HIV+ and HIV- women (p < 0.05). Among HIV- women, direct relationships were also observed between miR-155 and miR-125b (p= 0.004), miR-200c and miR-125b (p= 0.033), and miR-200c and p53 (p= 0.003). Conclusion: This study indicates that HIV upregulates p53 and miR-155, and downregulates miR-125b, miR-182, and miR-200c. This suggests that the upregulation of the tri-miRNA and downregulation of miR-155 through targeted therapy could mitigate HIV-associated immune activation thereby forestalling cervical cancer development.