A failure of the immune system to launch a strong and effective immune response to high risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal, successful therapeutic approaches also fail to induce clinical responses in a substantial

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... mber of cases. In this review we summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV induced neoplasia. We discuss the potential mechanisms involved in the escape of HPV-induced lesions from the immune system and indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. We conclude that there are a number of pre-existing conditions that determine the patient's responsiveness to immunotherapy and that an immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches will improve the clinical response rate.