Purpose of investigation: Purpose of this investigation was to determine the possibilities of non-surgical, medical treatment of high-grade squamous intraepithelial lesion (HSIL) of the vulva and differentiated type of vulvar intraepithelial lesions (VIN) and to determine the effect of medical treatment by local and systemic immunomodulators in relation to different histological types. Materials and Methods: The study included five patients with different histological types of VIN. The patients were given: systemic immunomodulator and antivirotics. After that, the patients initially included in the study were followed for a year, while the follow-up of the older patients group is still ongoing, and it has been six months since the completion of the treatment. Results: Combined medical therapy has positive therapeutic effect in the treatment of young HPV-positive adolescent patients with HSIL of the vulva. Medical treatment in HPV negative women with differentiated type VIN is less efficient, achieving partial remission in only 33% of patients. Conclusion: Combined medical therapy achieved better effects in hyperpigmented multifocal type of VIN.