β-glucans in HPV-Associated cervical cancer: current evidence and translational challenges

Cervical cancer continues to be a major cause of cancer-related morbidity and mortality worldwide despite advances in screening and HPV vaccination. Limitations of current therapeutic approaches, including toxicity, resistance, and suboptimal efficacy in advanced disease, have stimulated interest in complementary immunomodulatory strategies. β-glucans, naturally occurring polysaccharides derived from fungi, yeast, bacteria, cereals, and algae, have attracted increasing attention for their immunoregulatory and drug-delivery capabilities. Preclinical evidence, largely derived from non-cervical tumor models, indicates that β-glucans can modulate innate and adaptive immunity through receptors such as Dectin-1, complement receptor 3 (CR3), and Toll-like receptors, potentially remodeling the tumor microenvironment and enhancing antitumor responses. Direct evidence in cervical cancer remains comparatively limited but is emerging: a small randomized controlled trial recently demonstrated improved HPV clearance with topical β-glucans therapy, and historical trials from the 1980s-1990s reported benefit as a radiotherapy adjuvant in invasive cervical cancer, alongside direct cytotoxic activity observed in cervical cancer cell lined in vitro. In parallel, β-glucans-based delivery systems have shown potential for improving the stability, targeting, and controlled release of anticancer agents, though these platforms have likewise been validated primarily in non-cervical models. This review critically distinguishes cervical-specific evidence from findings extrapolated from other malignancies, identifies key evidence gap, including the scarcity of HPV-focused mechanistic studies and standardized formulations, and outlines priorities for future research toward the clinical translation of β-glucans in cervical cancer management.