The impact of gut microbiota on cervical cancer and precancerous lesions: neglected status, mechanisms, challenges, and a call to action.

Cervical cancer (CC) remains a major global health threat closely associated with persistent high-risk human papillomavirus (HPV) infection. Although immune checkpoint inhibitors (ICIs) have emerged as a therapeutic option, their objective response rates remain unsatisfactory. Variations in the local vaginal microbiota alone cannot fully explain inter-individual differences in HPV clearance, suggesting that additional systemic immune determinants are involved. The gut microbiota, a central regulator of host systemic immunity, can profoundly influence HPV clearance and antitumor immune responses by shaping dendritic cell (DC) function, modulating the Th1/Th2 balance, regulating regulatory T cell (Treg) expansion, and affecting natural killer (NK) cell activity. Emerging evidence indicates that specific gut microbial taxa are causally associated with HPV infection, cervical intraepithelial neoplasia (CIN), and cervical cancer, and may reshape the vaginal microecological environment and enhance immunotherapy responses. However, this dimension has long received insufficient attention. This Perspective systematically addresses four core issues: the neglected status of gut microbiota research and the functional boundaries of vaginal microecology; key mechanisms through which gut microbiota regulate HPV clearance and cervical lesion progression; major challenges restricting progress; and potential strategies for promoting clinical translation. This work aims to establish a theoretical framework for gut microbiota-based interventions in cervical cancer prevention and treatment, providing directional guidance for this emerging interdisciplinary field.