Human papillomaviruses (HPVs) have been identified as the etiological agent of cervical carcinoma, the second most common malignancy in women worldwide1. Currently, there are two different prophylactic HPV virus-like particle (VLP) vaccines (Gardasil and Cervarix) against HPV types. These vaccines are very efficient and have shown to prevent infections caused by these viruses but, these are not able effective in the elimination of pre-existing infection and HPV-related lesions. Therefore, the development of therapeutic vaccines against HPV-related cancers remains of utmost priority2. Since regression of lesions in HPV16-infected humans appears to be associated with Th1 and CD8+ T cell responses to the early proteins (especially E7 protein), an efficient therapeutic vaccination against HPV-associated disease will most likely depend on the induction of specific cellular immune responses 3. Therefore, HPV E7 is an ideal target antigen for developing therapeutic vaccines against HPV-associated neoplasms4. Nucleic acid vaccines potentially have a number of advantages over traditional attenuated, killed or subunit vaccines. They are cheaper and easier to produce than recombinant protein vaccines and they have fewer adverse side effects. One the other hand, these vaccines are less immunogenic than protein- or peptide based vaccines in larger animals and humans. Various strategies have been developed to enhance the potency of DNA vaccines including i) codon optimization and demethylating agents to improve antigen expression, ii) intracellular targeting strategies to improve MHC I and II presentation of antigen in DCs, iii) strategy to enhance the expression of MHC class I/II molecules iv) MHC class I single chain trimmer (SCT) technology to bypass antigen processing and presentation in DCs (1). Codon optimization is a commonly used strategy to enhance the expression of antigen encoded by the DNA vaccine. Codon optimization refers to the modification of antigenic gene sequences by replacing codons that are rarely recognized by cellular protein synthesis machinery with codons that are more commonly recognized. For example, mice immunized with codon-optimized HPV-16 E6 DNA were shown to generate enhanced antigen-specific CD8+ T cell immune responses compared to mice immunized with wild-type E6 DNA 3. In addition, a DNA vaccine containing codon-optimized modified E7 gene was also shown to be effective in generating antigen-specific T cell immune responses and protective antitumor immunity in vaccinated mice 4. Co-administration of DNA encoding optimized antigen with adjuvant cytokines may be a strategy to increase cellular immune responses to a DNA vaccine. The cytokine IL-12 expressed by B cells and macrophages is critical in priming T1 responses that are centrally involved in T cell-mediated protection against many pathogens, including intracellular parasites and viruses 7. Recently, IL-12 has been identified as a powerful adjuvant substance in a variety of vaccination models of infectious disease. Here, we used the optimized E7 oncogene to significantly improve the weak immunogenicity of the HPV tumor antigen E7. As an alternative approach, that co-injection of optimized antigen with IL12 is effective in the development of a protective Th1 immune response and in controlling the progression of tumor these animal models.