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Vaccinia-Expressed Human Papillomavirus 16 and 18 E6 and E7 as a Therapeutic Vaccination for Vulval and Vaginal Intraepithelial Neoplasia

Departments of Gynaecological Oncology [P. J. B., J. A. L.], Dermatology [J. C. S.], and Pathology [R. P. M.], Addenbrooke’s National Health Service Trust, Cambridge CB2 2QQ, United Kingdom; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom [P. J. B., N. C., M. A. S., J. C. S.]; Xenova Group plc., Cambridge CB4 0WG, United Kingdom [C. M. B., J. K. H., J. D., J. S. C. R.]; and Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands [S. H. v. d. B., R. O.]

Purpose: Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia.

Experimental Design: Twelve women, aged 42–54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18.

Results: The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN- enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides.

Conclusions: The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.

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