Human papillomavirus (HPV)-associated intraepithelial
neoplasia or
cancers are ideal candidates for
cancer immunotherapy since HPV
oncoproteins, such as E6 and E7
proteins of high-risk HPVs, could be utilized as foreign
antigens. In HPV-associated
cancers as well as nonviral
cancers, the
cancer cells may evade host immunity through the expression of
immune checkpoint molecules, downregulation of
human leukocyte antigen, and activation of immune regulatory cells. Because of these immune suppressive mechanisms, HPV therapeutic
vaccines have shown little efficacy against HPV-associated
cancers, although they have shown efficacy in treating HPV-associated intraepithelial
neoplasias. Recently, checkpoint blockade emerged as a promising new treatment for solid
cancers; however, these
therapies have shown only modest efficacy against HPV-associated
cancers. Here we reviewed literature analyzing a combinatory
therapy using an
immune checkpoint inhibitor and an HPV therapeutic
vaccine for treating HPV-associated
cancers to compensate for shortfalls of each monotherapy. Complimentary modes of T cell activation would be deployed; as
vaccines would directly stimulate the T cells, while checkpoint inhibitors would do so by releasing inhibition. Some promising studies using animal models and early human clinical trials raised a possibility that such combinations may be efficacious in regressing HPV-associated
cancers.
Epitope spreading (the phenomenon in which non-targeted
antigens become new targets of immune response) may play a critical role mechanistically. Currently ongoing studies will shed light as to whether such combination
therapy would indeed be a promising new treatment paradigm. Current and future studies must also determine the adverse effect profile of such a combination treatment.