In summary, our data demonstrates CD40 potentiates the antigen-specific CD8+ Tscm cells through Wnt/β-catenin signaling to facilitate the effective long-term CD8 T cell based immunotherapy, and could develop an optimal immunization strategy against cervical cancer, and these HPV16-specific Tscm cells are associated with progression risks in CSCC patients. Here, CD40 is linked to skin squamous cell carcinoma.