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Spontaneous Regression of Grade 3 Vulvar Intraepithelial Neoplasia Associated with Human Papillomavirus-16–Specific CD4⁺ and CD8⁺ T-Cell Responses

¹ Service de Dermatologie and ² Service d’Anatomie pathologique, Université Versailles Saint Quentin en Yvelines, Hôpital Ambroise Paré, Boulogne-Billancourt, France; ³ Institut Cochin, Département d’Immunologie, Institut National de la Santé et de la Recherche Médicale U567, Centre National de la Recherche Scientifique Unité Mixte et de Recherche 8104, Groupement de recherche 2826, Institut Fédératif de Recherche Alfred Jost - Université René Descartes, Hôpital Cochin, Paris, France; ⁴ Service d’Anatomie pathologique, Hôpital Jean Verdier, Bondy, France and EA3406, Unités de Formation et de Recherche Santé, médecine et biologie humaine, Université Paris XIII; ⁵ Service d’Histologie-embryologie cytogénétique –Anatomie pathologique, Hôpital Saint Vincent de Paul, Paris, France; and ⁶ Commissariat à l’Energie Atomique Département d’Ingénierie et d’Etudes des Protéines, Gif sur Yvette, France

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 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.

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