The combined HPV16-E2/E6/E7 T cell response in oropharyngeal cancer predicts superior survival

Tumor-infiltrating HPV16-E2-specific CD8(+) T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4(+) T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16(+) OPSCC cohort, we regularly detect HPV16-E2-specific CD4(+) and CD8(+) intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.