Immunological and antitumor responses to HPV-targeted therapeutic vaccines in preclinical models of head and neck cancer: a systematic review.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasingly prevalent and accounts for 22-70% of HNSCCs depending on the region. Although prophylactic HPV vaccines were approved in the early 2000s to prevent HPV infection and oncogenesis, they are ineffective against established HPV infections and related cancers. The standard of care for these HPV-associated oropharyngeal cancers combines radiotherapy, surgery, and chemotherapy. However, these treatments can result in significant lifelong side effects for patients with no new treatments entering regular clinical practice in the past decade. Therapeutic cancer vaccines represent an opportunity for novel treatment approaches in HPV-associated cancer, particularly because these cancers display viral tumor-specific antigens (TSAs) such as E6 and E7, making them easily targetable by this type of immunotherapy. Currently, there are no FDA-approved therapeutic vaccines for HPV-associated cancers, but preclinical and clinical studies are ongoing in this area. In this systematic review, we describe current HPV vaccination strategies, their biological mechanisms, and their immunological and therapeutic effects in preclinical cancer models. We discuss each component of therapeutic vaccines: antigens, delivery platforms, adjuvants, and combination agents. We also assess the results of recent preclinical studies evaluating HPV therapeutic vaccines to provide an outlook on the future of this treatment modality.