Recently, a new class of drugs, called checkpoint inhibitors (CI), has shown encouraging results in potentiating the immune response. The targets of these drugs are immune checkpoint molecules expressed on immune cells (CTLA4 and PD1 ) and their ligand (PDL1), which is usually effective in mediating signals to attenuate the immune reactions. The binding of these molecules by CI is the trigger in determining the T-cell activation during T cell priming.
Nivolumab and pembrolizumab are mAb directed against the PD-1 receptors. They produced durable responses in approximately 20% of unselected patients with advanced non-small cell lung cancer (NSCLC). In Europe, the use of CI is approved for metastatic melanoma (Ipilimumab, Pembrolizumab) and I/II line NSCLC (Nivolumab). Thanks to their selective action on immune cells, their toxicity profile is favourable.
The low toxicity profile and the encouraging immunotherapeutic effects, supported the experimentation of immune checkpoint inhibitors in several fields. Several trials are currently testing these molecules in combination with chemotherapy in other malignancies, including cervical cancer. Recently, immunotherapy against HPV using a viral gene delivery platform to immunize against HPV 16 (genes E6 and E7), combined with PD-1 blockade, has shown to increase therapeutic effect in mouse with cervical cancer as compared to the vaccine alone. Analysis of the microenvironment and of the subpopulation lymphocytes revealed that when CI have been administrated, a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1(+) TILs is observed.
In this proposal, we hypothesize that patients with chronic HPV infection who are receiving systemic treatment with immune check point inhibitors for a different indication will clear their HPV infection significantly more often as compared to a control group of patients with chronic HPV infection.
76 patients (19 cases and 57 controls) will be enrolled in the study.
