title: Spontaneous regression of grade 3 vulvar intraepithelial neoplasia associated with human papillomavirus-16-specific CD4(+) and CD8(+) T-cell responses.
abstract: 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-IFNgamma 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 HPV-specific 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.
authors.affiliation: Service de Dermatologie and Service d'Anatomie pathologique, Université Versailles Saint Quentin en Yvelines, Hôpital Ambroise Paré, Boulogne-Billancourt, France. bourgault@cochin.inserm.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourgault Villada
authors.forename: Micheline
authors.initials: M
authors.lastname: Moyal Barracco
authors.forename: Isabelle Bourgault
authors.initials: IB
authors.lastname: Villada
authors.forename: Micheline Moyal
authors.initials: MM
authors.lastname: Barracco
authors.forename: Marianne
authors.initials: M
authors.lastname: Ziol
authors.forename: Aude
authors.initials: A
authors.lastname: Chaboissier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barget
authors.forename: Sophie
authors.initials: S
authors.lastname: Berville
authors.forename: Bernard
authors.initials: B
authors.lastname: Paniel
authors.forename: Eric
authors.initials: E
authors.lastname: Jullian
authors.forename: Thierry
authors.initials: T
authors.lastname: Clerici
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillère
authors.forename: Jean Gérard
authors.initials: JG
authors.lastname: Guillet
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002278:Carcinoma in Situ / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16