HPV-Specific Immunotherapy: Key Role for Immunomodulators

Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic.