This proposal projects a phase I trial including up to 24 patients with CIN 2-3 treated with a DNA plasmid vaccine directed against the E7 protein of HPV 16. The goals of this trial are to define the toxicity and tolerability of the vaccine given over a four month period of time at three week intervals. This phase I trial will define the MTD for the vaccine (the dose at which 33% of the patients have dose-limiting toxicity. After this, the investigators plan a phase II study designed as a two-phase trial after the method of Simon. This trial will accrue 22 patients with CIN 2-3 who are HLA-A2 positive and HPV 16 positive and have a negative endocervical curettage. If there are at least 8 responders, the trial will proceed to a second phase of accrual of up to 46 patients. The phase II trial will define the clinical, immunological, and anti-viral effects of the MTD. The primary end-point of the phase II trial will be digitally determined regression of the area of CIN determined at colposcopy. Other end-points will include: disappearance of the virus in a specimen resected by LEEP one month after the completion of the vaccine; two-fold increase in release of gamma interferon in the cytokine release assay; and a five-fold increase in CTL frequency in the tetramer assay. To insure that spontaneous regression does not account for a portion of the responses, baseline measurements will be followed one month later by a second set of assessments prior to the start of the vaccine.
