Persistent high-risk Human Papillomavirus infection is the primary factor in cervical carcinogenesis. However, other host-related features are believed to play a role as well. Recent research suggests that the vaginal microbiome and the immune microenvironment play a significant role in the acquisition and persistence of Human Papillomavirus infection, as well as in the regression or progression of cervical intraepithelial lesions. Studies in this emerging field describe factors associated with this interaction, though the precise nature remains incompletely understood. In this narrative review, we aim to summarize the current literature on the topic and propose hypotheses and recommendations for future research and treatment strategies.

Cervical cancer remains one of the most common malignancies among women worldwide, and treatment of locally advanced disease is often associated with substantial toxicity that negatively affects the quality of life. Therefore, strategies aimed at improving survival while minimizing treatment-related side effects are essential. Emerging evidence suggests that the gut and vaginal microbiomes influence cervical carcinogenesis, treatment response, and treatment-related adverse effects. This narrative review aims to summarize current evidence regarding the role of the gut and vaginal microbiomes in locally advanced cervical cancer and explores their potential clinical implications, including interactions with immunological mechanisms. Dysbiosis has been associated with chronic inflammation, impaired antitumor immune responses, reduced treatment efficacy, and increased toxicity, whereas a beneficial microbial composition appears to support improved therapeutic outcomes and reduced toxicity. In addition, microbiome-targeted interventions, including probiotics, show promise in modulating microbial composition, optimizing treatment outcomes, and mitigating treatment-related toxicity. Longitudinal studies integrating analyses of both the gut and vaginal microbiomes with immune infiltrates, patient-reported outcomes, and clinical treatment results are essential to clarify the therapeutic potential of microbiome-targeted interventions in personalized cervical cancer care. Particular attention should be given to interactions between the microbiome and immunotherapy, as immune checkpoint inhibitors are increasingly being incorporated into treatment strategies for locally advanced disease.