Background: Human papillomavirus (HPV) has been implicated in the pathogenesis of 15% to 23% of head and neck squamous cell carcinomas as well as most oropharyngeal carcinomas. The viral oncoproteins E6 and E7 are expressed in HPV-positive tumor cells and therefore provide ideal targets for tumor immunotherapy. Because of its unique ability to induce a cellular immune response, the intracellular bacteria Listeria monocytogenes has been studied as a potential HPV-positive tumor vaccine. Objective: To present a new recombinant strain of L monocytogenes that is effective in treating HPV-positive tumors in a murine model. Design: A new recombinant L monocytogenes vaccine, Lm-ActA-E7, was designed by transforming an attenuated Listeria strain with an E7 expression cassette. The cassette consists of the HPV-16 E7 sequence fused to the Listeria protein ActA. The resultant strain of bacteria secretes E7 antigen as a fusion protein with ActA.

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Objective: To test whether an E7 peptide/CpG vaccine is effective in preventing and treating human papillomavirus-positive tumors in a murine model. Intervention: First, an E7 peptide/CpG vaccine was administered systemically on days −14 and −7, and tumor cells were injected subcutaneously on day 0. Second, tumor cells were injected on day 0, and vaccine was administered on days 7, 14, and 21. Main Outcome Measures: Tumor size was measured 3 times per week. A tetramer assay was used to assess the presence of activated, E7-specific lymphocytes in spleen and tumor cells harvested from mice treated with a similar vaccination regimen. Results: In the prophylactic study, 75% of mice injected with E7 peptide/CpG resisted tumor formation. In the therapeutic setting, tumors initially regressed and experienced delayed progression when compared with controls. Survival rates improved in E7/CpGvaccinated mice. Tetramer analysis detected increased numbers of activated, E7-specific lymphocytes in the spleens and tumors of animals treated with the experimental vaccine when compared with controls. Conclusion: The use of CpG motifs as an adjunct to peptide-based immunotherapy has potential impact on the treatment of human papillomavirus-associated cancers.