For debate: that Australia should continue using the quadrivalent vaccine

Abstract

Australia was the first country to introduce a governmentfunded, population-based mass vaccination program against human papillomavirus (HPV) using the quadrivalent HPV vaccine. Against a backdrop of a highly successful cytology based cervical screening program and one of the lowest cervical cancer incidence and mortality rates in the world, the Australian Government recognised the health and economic impacts of adding the HPV vaccination to the existing screening program. The favourable statistics about cervical cancer in Australia are the result of a very intensive screening program with a high rate of clinical interventions, including Pap tests, colposcopies and definitive surgical therapies on the cervix, all with the potential for increasing morbidity in the screened population. Cost-effectiveness modelling has demonstrated that a universal vaccination program with the quadrivalent vaccine was a cost-effective health intervention, expecting further reductions in the incidence of cervical cancer and other HPV-related disease, and significant reductions in the clinical interventions that were associated with cervical cancer prevention via screening alone. On the basis of its economic analysis, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended the implementation of a vaccination program based on on-going vaccination of 12-year-old girls and a 2-year catch-up program for girls and women aged between 13 and 26 years. Interim data about the program already suggest very high coverage and participation rates, with indications of high community awareness and acceptance of the program among health providers and the community. Preliminary data on the prevalence of genital warts have confirmed the early population benefits from this program that were originally predicted. The time from infection to clinical disease with low-risk types, such as 6 and 11, is usually much shorter than for oncogenic varieties and so the impact on the prevalence of genital warts in the community following vaccination is the first health outcome expected. Indeed, the evidence of some level of herd immunity, as demonstrated by the reduction in genital wart prevalence in non-vaccinated males in this study, suggests that the population benefits of the vaccination program will exceed those predicted by the relatively conservative cost-effectiveness modelling. Given that the quadrivalent HPV vaccination program is now well established in Australia and the expected benefits of the program are already being confirmed, the question arises as to whether there would be any gains in modifying the program and replacing the quadrivalent vaccine with the bivalent vaccine. To consider this question, it is necessary to compare the two vaccines in relation to their individual components, particularly HPV 16 and 18, which are present in both vaccines, and the separate additional protection offered by the HPV types 6 and 11 in the quadrivalent vaccine. The latter is obviously absent from the bivalent vaccine. Considerable marketing efforts have been made to compare the two vaccines in relation to the HPV 16 and 18 components. There are very clear differences in manufacturing processes of these biological agents and so it would not be a surprise if there were some subtle differences between the two vaccines. Claims for differing efficacies, however, have been difficult to interpret due to the markedly different populations and subpopulations used in each of the vaccine trials, making direct comparisons of the trials impossible. Depending upon the populations studied, both vaccines demonstrate high efficacy against vaccine type specific infections and neoplastic lesions. Claims and counter-claims for cross-protection against other non-vaccine types have been made, alleging the superiority of one or other of the vaccines. It would seem that both vaccines offer some limited protection against a range of non-vaccine types in relation to the prevention of cervical lesions. The relative infrequency of these lesions in a clinical setting, however, and the fact that the clinical trials were not powered or designed to study these aspects make it difficult to assess the clinical importance of these observations. There are relatively low levels of type specific antibodies raised against these non-vaccine types compared with those seen with the vaccine types, raising issues regarding the likely duration of protection from these cross-protective antibodies. Finally, both companies have publicly acknowledged that they are developing multivalent vaccines, suggesting that the companies themselves do not see cross-protection as an important component of the existing vaccines. Similar claims about antibody levels and duration of protection have been made in relation to the alleged superiority of one vaccine or another. Although there is no correlation between disease efficacy and antibodies, the clinical impact of higher level of antibodies remains uncertain. Both vaccines have maintained high levels of efficacy with no reported breakthrough disease. Indeed, it seems clear that CSIRO PUBLISHING Editorial