Nature Communications, Published online: 13 June 2026; doi:10.1038/s41467-026-74318-z Mechanisms underlying effective immune escape in HPV-associated oropharyngeal cancers despite the presence of immune cells are incompletely understood. Here, authors use single-cell spatial analysis to show that tumors form distinct local immune niches, including hypoxic regions and chemokine foci, that shape immune cell composition and support cancer cell states able to evade HPV-specific T cell responses.