The Potential of Immune Checkpoint Blockade in Cervical Cancer: Can Combinatorial Regimens Maximize Response? A Review of the Literature.

OPINION STATEMENT: Cervical cancer (CC) is most often caused by the human papillomavirus (HPV). In principle, these ties to the virus should make HPV tumors a relatively easy target for clearance by the immune system. However, these HPV-associated tumors have evolved strategies to escape immune attack. Checkpoint inhibition immunotherapy, which has had remarkable success in cancer treatment, has the potential to overcome the immune escape in CC by harnessing the patient's own immune system and priming it to recognize and kill tumors. Recent work involving PD-1/PD-L1 inhibitors in CC lends credence to this belief, as pembrolizumab has shown evidence of clinical efficacy and consequently been granted accelerated approval by the FDA. That being said, the oncologic outcomes following monotherapy with these biologics have mostly been modest and variable, and this can be attributed to alternative resistance mechanisms to tumor response. The use of therapies that stimulate immune responses via checkpoint-independent activation will therefore augment release of T cell inhibition by checkpoint inhibitors for stronger and more sustained clinical responses. Such a combinatorial approach holds promise for weak- or non-responders to checkpoint therapies as supported by evidence from various, recent pre-clinical, and preliminary clinical studies.