Evaluation of vaccine efficacy (VE) against individual non-vaccine carcinogenic HPV types and related disease among women in a TVC-naïve cohort: a pooling effort using data from HPV-008 and HPV-009

Trial description: A new theory for the AS04-HPV-16/18 (bivalent) vaccine is emerging: that there are low levels of cross protection against many carcinogenic HPV types that are not able to be quantified given sample size limitations in individual trials. By pooling the large HPV-008 and -009, we would be able to better understand the actual effects of the vaccine against each carcinogenic HPV type, as well as HPV 6 and 11. Further, we could more precisely quantitate the reductions in cytology and histology outcomes across these HPV infections in an HPV-naïve cohort. Such an analysis could work to challenge the assumption that increased valency is what matters most in a vaccine to provide maximum disease protection, and could shed light on the unrecognized benefits of the bivalent vaccine. Additionally, new questions are emerging focused on whether antibodies control infection rates and more broadly cross-reactive Th1 responses control progression to disease. We aim to investigate whether a reduction in both infection and progression rates is observed among vaccinees compared with control participants. Based on the emerging GSK model, women with prior infection with a non-vaccine type may have a pre-existing bias toward a Th2 response to L1 that will not be overcome by vaccination.