Background: HPV associated oropharyngeal cancers (OPC) are increasing in prevalence worldwide. Treatment of disease recurrence, either locoregionally or distant, after primary chemoradiotherapy or surgery is not uncommon, and poses a difficult management dilemma with limited success. Polynucleotide vaccines encoding HPV16 E6/E7 fusion proteins have demonstrated efficacy in several animal models of HPV associated cancer.
Aim: Evaluate a polynucleotide immunotherapy targeted at HPV16 E6 and E7 proteins for immunogenicity and safety in patients with apparent cure after primary therapy for HPV associated OPC.
Methods: A 1:1 mixture of 2 codon modified polynucleotide vaccines encoding HPV16 E6 and E7 with or without ubiquitin were administered at three doses (0.25mg, 1mg, 4mg) intracutaneously on 3 occasions, 4 weekly, to a total of 12 subjects with treated HPV associated OPC.
Results: A cell mediated response to HPV 16 E6 and E7 was evident at baseline in all participants using ELISpot. Antibodies against HPV 16 E7 was evident at baseline in 11 of 12 participants using ELISA. Of 12 subjects, 10 demonstrated a significant immune response to one or more of the peptide pools at one or more timepoints. One subject has had a confirmed recurrence of disease 6 months after immunisation. Only minor local adverse events attributable to the vaccine at the site of injection were observed.
Conclusion: This polynucleotide vaccine enhanced specific immunity to a virus derived tumour associated antigen in the majority of immunised subjects without significant adverse events, warranting a further study in subjects with recurrent disease after treatment.
This study was conducted with the approval of the Australian Therapeutic Goods Administration and the Ethics committee of the Princess Alexandra Hospital.