Current status of therapeutic HPV vaccines.

The accumulating successes of immune-based treatments for solid tumors have prompted an explosion of cancer clinical trials testing strategies to elicit tumor-specific immune effector responses, either alone, in combination with immune checkpoint blockade, or with conventional cancer treatment modalities. However, across the board, clinical responses have been achieved in only a limited subset of cancer patients, underscoring a critical need to identify mechanisms and biomarkers of response, as well as mechanisms of resistance to therapy. Cancers caused by human papillomavirus (HPV) are driven by two viral oncoproteins, E6 and E7, both of which are functionally required for cellular transformation, thereby providing non-'self', tumor-specific antigenic targets. Immune responses that are specific for either or both of these oncoproteins can be used to follow the magnitude and kinetics of immune responses to therapeutic interventions. Moreover, identifying neoantigens is not a concern in early-stage disease - since HPV cancers are driven by HPV oncoproteins, the somatic mutational load in early disease is low, particularly in comparison to non-HPV-related squamous cancers arising in the same organ site [1,2]. Cancers caused by HPV are a model clinical setting in which to test principles of immunotherapies, and to discover mechanisms of interactions between tumors and their attendant immune milieu. In this review, we will use examples of insights gained from studies of HPV disease to illustrate major themes of immune-based therapeutic strategies.