The present invention provides methods of mucosal tissue administration of therapeutic HPV vaccines, in a prime-boost regimen, which generated antigen-specific CD8+ T cell-mediated immune responses and the expression of tissue-resident memory T cell (Trm) markers on the CD8+ T cells. In some embodiments, the inventive methods employed pNGVL4a-sig/E7(detox)/HSP70 DNA vaccine and TA-HPV in a prime-boost regimen which shows vaccination in the infected mucosal tissues, including those in the cervicovaginal tract, elicited potent antitumor effects and a more effective local immune response in the tissues and regional lymph node, when compared to intramuscular vaccination. Furthermore, targeting the induction of Trm-mediated immune responses can serve as an ideal methodology especially for therapeutic HPV vaccines.
