Transformation by high-risk HPV is the consequence of persistent infections

Recently, two prophylactic vaccines against the most significant oncogenic human papillomaviruses (HPV; 16 and 18) became available that efficiently protect against persistent HPV infection and cancer precursors. However, clinical trials performed with these vaccines did not provide evidence that they would influence the natural history of prevalent HPV infections, that is, their eventual malignant progression. Because, even under the optimistic assumption of high vaccine coverage, a significant reduction of cancer incidence can only be expected after two decades, there is a need for immune therapeutic strategies to be offered to persistently infected individuals who do not benefit from the prophylactic vaccines. Here, we describe the reasons for failure of most of the published approaches to HPVspecific therapies, highlight promising developments and present our view for future developments.