HPV-dependent divergence of B cell immunity in head and neck squamous cell carcinoma

• B cells display dual roles in HNSCC, contributing to both anti-tumor and pro-tumor immunity. • HPV status profoundly shapes B cell composition, distribution, and differentiation in the tumor microenvironment. • Distinct molecular dynamics underlie HPV-driven modulation of B cell fate and function. • Insights into B cell plasticity provide new opportunities to optimize immunotherapy for HNSCC. The immune microenvironment in head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and dynamic system that plays a crucial role in tumor progression and therapeutic response. While T cell-mediated immunity has been extensively studied, B cells, an equally important component of the adaptive immune system, are gaining increasing attention for their diverse and sometimes contradictory roles within the HNSCC tumor microenvironment (TME). The plasticity of B cells contributes to both anti-tumor and pro-tumor immunity through different mechanisms, highlighting their dual regulatory capacity. Human papillomavirus (HPV) infection, a critical etiological factor and prognostic marker in HNSCC, significantly influences the composition, distribution and functional state of B cells in the TME. In this review, we systematically examine the phenotypic and functional differences in B cell populations in HPV + versus HPV − HNSCC. We further discuss how HPV status shapes B cell behavior and propose that elucidating the signaling pathways and differentiation trajectories influenced by HPV could reveal critical mechanisms of B cell-mediated immunity. These insights hold potential for refining immunotherapeutic strategies and improving clinical outcomes for HNSCC patients.