Inclusion of the benefits of enhanced cross-protection against cervical cancer and prevention of genital warts in the cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands

Abstract

BackgroundInfection with HPV 16 and 18, the major causative agents of cervical cancer, can be prevented through vaccination with a bivalent or quadrivalent vaccine. Both vaccines provide cross-protection against HPV-types not included in the vaccines. In particular, the bivalent vaccine provides additional protection against HPV 31, 33, and 45 and the quadrivalent vaccine against HPV31. The quadrivalent vaccine additionally protects against low-risk HPV type 6 and 11, responsible for most cases of genital warts. In this study, we made an analytical comparison of the two vaccines in terms of cost-effectiveness including the additional benefits of cross-protection and protection against genital warts in comparison with a screening-only strategy.MethodsWe used a Markov model, simulating the progression from HPV infection to cervical cancer or genital warts. The model was used to estimate the difference in future costs and health effects of both HPV-vaccines separately.ResultsIn a cohort of 100,000 women, use of the bivalent or quadrivalent vaccine (both at 50% vaccination coverage) reduces the cervical cancer incidence by 221 and 207 cases, corresponding to ICERs of €17,600/QALY and €18,900/QALY, respectively. It was estimated that the quadrivalent vaccine additionally prevents 4390 cases of genital warts, reducing the ICER to €16,300/QALY. Assuming a comparable willingness to pay for cancer and genital warts prevention, the difference in ICERs could justify a slightly higher price (~7% per dose) in favor of the quadrivalent vaccine.ConclusionsClearly, HPV vaccination has been implemented for the prevention of cervical cancer. From this perspective, use of the bivalent HPV vaccine appears to be most effective and cost-effective. Including the benefits of prevention against genital warts, the ICER of the quadrivalent HPV vaccine was found to be slightly more favourable. However, current decision-making on the introduction of HPV is driven by the primary cervical cancer outcome. New vaccine tenders could consider the benefits of cross-protection and the benefits of genital warts, which requires more balanced decision-making.

The cost–effectiveness of HPV vaccination in addition to screening: a Dutch perspective

“…Most of the studies [8] examined the cost-effectiveness of HPV vaccination for young girls aged 10-12 [14][15][16][17]19,30,32,33]. Almost half of the studies [4] investigated the influence of adding HPV vaccination to cervical screening only [14][15][16][17].…”

“…Almost half of the studies [4] investigated the influence of adding HPV vaccination to cervical screening only [14][15][16][17]. Moreover, two studies explored various strategies, either the addition of specific screening techniques to vaccination [16,19] or explicit comparisons between the quadri-and bivalent vaccine [32]. Coupe et al also explored the influence of various screening strategies (HPV DNA vs cytology and 4-7 screenings during specific age periods) and cross-protection in addition to direct protection [19,30].…”

“…(2013) [32] Luttjeboer et al (2013) [17] Diagnosis The cost-effectiveness of HPV vaccination in addition to screening Review informahealthcare.com the full impact of HPV vaccination, the implementation of the program should be considered from a broad perspective (e.g., societal perspective) within a long-term time frame. Moreover, the perspective chosen for a model should reflect the core considerations of the relevant decision makers involved.…”

“…In this review, almost all studies (90%) applied this societal perspective, in line with Dutch overall recommendations for costeffectiveness. To cover all possible costs, savings and outcomes of both HPV vaccination and cervical cancer screening, a lifetime horizon is crucial [28,29] and indeed most of the studies (80%) applied a lifetime horizon in their models [14,[16][17][18][19][30][31][32].…”

Cross-Reactivity, Epitope Spreading, andDe NovoImmune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines

“…However, some level of cross-protection against nonvaccine HPV types has been demonstrated for the prophylactic vaccines Gardasil and Cervarix (7)(8)(9)(10)(11)(12)(13)(14). In the phase III randomized, doubleblinded clinical trial examining the efficacy of Cervarix, Paavonen et al observed vaccine efficacy not only against cervical intraepithelial neoplasias of grade 2 and worse (CIN2ϩ) associated with HPV-16 and -18 but also against CIN2ϩ associated with HPV-31, -33, and -45 (11).…”