A therapeutic DNA vaccine encoding human calreticulin (CRT) linked to human papillomavirus (HPV) type 16 E6, E7, and L2 proteins, with potential immunomodulating and antineoplastic activities. Upon administration via intramuscular injection with electroporation, the pNGVL4a-CRT-E6E7L2 DNA vaccine expresses HPV16 E6, E7 and L2 proteins, which may elicit a cytotoxic T-lymphocyte (CTL) response and humoral immune responses against tumor cells expressing these proteins, resulting in tumor cell lysis and tumor cell death. In addition, HPV16 L2-specific neutralizing antibody may prevent a broad spectrum of HPV infections and HPV-associated cancers. The heat shock protein CRT may potentiate MHC class I presentation to antigen-specific CD8-positive T-cells, enhancing the induction of cellular immunity and the potency of the vaccine.