Human papilloma virus type 16 (HPV‐16) is the HPV most frequently associated with cervical carcinoma in humans. For the prevention or treatment of cervical carcinoma, the E6 and E7 oncoproteins appear to be good targets for vaccine‐induced cytotoxic T lymphocytes (CTL). Lipopeptide vaccination is an efficient way of stimulating cellular responses. However, to synthesize effective lipopeptides, it is necessary to define which epitopes are immunogenic. In this study we first determined that peptide 80 – 88 of the E6 protein was recognized by CTL from a healthy donor in association with the HLA‐B18 molecule. We then defined the HLA‐B18 anchoring peptide motif by testing the binding of various short peptides with the HLA‐B18 molecule and showed that it was related to the HLA‐A1‐specific peptide motif. Furthermore, in analyzing the potential E7 epitopes susceptible to associating with HLA‐B18, we demonstrated that peptide E7 44 – 52 gave the strongest binding. It could also be recognized by CTL from peripheral blood mononuclear cells (PBMC) of the same healthy donor. Finally, with PBMC from a patient with a cervical intraepithelial neoplasia grade 3, we found CTL which recognized the E6 80 – 88 epitope. We have hence identified two peptides encoded by the E6 and E7 proteins which are presented by the HLA‐B18 molecule and could be included in a vaccine against HPV‐16.

Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in six patients affected with grade 3 vulvar intraepithelial neoplasia (VIN3, also known as bowenoid papulosis). Five of the patients presented with a chronic and persistent disease that relapsed after destructive treatments. They showed no detectable anti-HPV blood T-cell responses and no T-cell intraepidermal vulvar infiltrate containing both CD4؉ and CD8؉ lymphocytes. The last patient had a complete clearance of viral lesions, 8 months after disease onset and 2 months after electrocoagulation of <50% of the VIN3 lesions. She showed high frequency anti-E6 and anti-E7 effector blood T cells by ex vivo ELISpot-IFN␥ assay before clinical regression. Immunohistochemical study of her vulvar biopsy revealed a marked dermal infiltrate containing a majority of CD4؉ T lymphocytes and an epidermal infiltrate made up of both CD4؉ and CD8 ؉ T cells. This seems to be the first evidence of an association between spontaneous regression of VIN3 lesions and HPVspecific T-cell responses detectable in the blood. Hence, an increase of HPV-specific effector T lymphocyte responses by vaccine-based therapeutic strategies might be useful to clear the lesions in bowenoid papulosis disease.