Ecological validity of cost-effectiveness models of universal HPV vaccination: A systematic literature review

BACKGROUND: The protective (herd) effect of the selective vaccination of pubertal girls against human papillomavirus (HPV) implies a high probability that one of the two partners involved in intercourse is immunised, hence preventing the other from this sexually transmitted infection. The dynamic transmission models used to inform immunisation policy should include consideration of sexual behaviours and population mixing in order to demonstrate an ecological validity, whereby the scenarios modelled remain faithful to the real-life social and cultural context. The primary aim of this review is to test the ecological validity of the universal HPV vaccination cost-effectiveness modelling available in the published literature. METHODS: The research protocol related to this systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42016034145). Eight published economic evaluations were reviewed. RESULTS: None of the studies showed due consideration of the complexities of human sexual behaviour and the impact this may have on the transmission of HPV. DISCUSSION: Our findings indicate that all the included models might be affected by a different degree of ecological bias, which implies an inability to reflect the natural demographic and behavioural trends in their outcomes and, consequently, to accurately inform public healthcare policy. In particular, ecological bias have the effect to over-estimate the preference-based outcomes of selective immunisation. A relatively small (15-20%) over-estimation of quality-adjusted life years (QALYs) gained with selective immunisation programmes could induce a significant error in the estimate of cost-effectiveness of universal immunisation, by inflating its incremental cost effectiveness ratio (ICER) beyond the acceptability threshold. The results modelled here demonstrate the limitations of the cost-effectiveness studies for HPV vaccination, and highlight the concern that public healthcare policy might have been built upon incomplete studies.