Nicolas Van de Velde

Economic Evaluation of Human Papillomavirus Vaccination in Developed Countries

Background: With promising efficacy results from randomized control trials of human papillomavirus (HPV) vaccines and the availability of new screening paradigms, policymakers are being asked to make recommendations and decisions regarding the optimal strategies to reduce HPV infection and disease. Such decisions are increasingly being made with significant input from mathematical and economic models. The demand for modeling has resulted in the publication of numerous mathematical models looking at the cost-effectiveness of HPV vaccination. Objective: To review published models that have been used to evaluate the cost-effectiveness of HPV vaccination in developed countries and highlight points of consensus and disagreement in methods and findings. Methods: This review consists of cost-effectiveness studies published in the peer-reviewed literature before August 2008. Results: Despite variations in methods, modeling studies are producing consistent conclusions: (1) vaccinating young girls against HPV is likely to be cost- effective; (2) vaccinating boys will most likely not be cost- effective in countries that can reach high coverage rates in girls, and (3) results are most sensitive to the duration of vaccine protection. However, results from analyses examining the effectiveness and cost-effectiveness of vaccinating boys when coverage rates are low (≤80%) and catch-up strategies have reached conflicting conclusions.

Incremental Impact of Adding Boys to Current Human Papillomavirus Vaccination Programs: Role of Herd Immunity

Our aim was to examine the potential incremental impact of vaccinating boys against human papillomavirus (HPV) on vaccine-type infection in females and males, using an individual-based HPV transmission-dynamic model. Under base assumptions (vaccine efficacy = 99%, duration of protection = 20 years, coverage = 70%), vaccinating 12-year-old boys, in addition to girls, resulted in an incremental reduction in HPV-16/18 (HPV-6/11) incidence over 70 years of 16% (3%) in females and 23% (4%) in males. The benefit of vaccinating boys decreased with improved vaccination coverage in girls. Given the important predicted herd immunity impact of vaccinating girls under moderate to high vaccine coverage, the potential incremental gains of vaccinating boys are limited.

Population-Level Impact of the Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines: A Model–Based Analysis

BACKGROUND Bivalent and quadrivalent human papillomavirus (HPV) vaccines are now licensed in several countries. Furthermore, clinical trials examining the efficacy of a nonavalent vaccine are underway. We aimed to compare the potential population-level effectiveness of the bivalent, quadrivalent, and candidate nonavalent HPV vaccines. METHODS We developed an individual-based, transmission-dynamic model of HPV infection and disease in a population stratified by age, gender, sexual activity, and screening behavior. The model was calibrated to highly stratified sexual behavior, HPV epidemiology, and cervical screening data from Canada. RESULTS Under base case assumptions, vaccinating 12-year-old girls (70% coverage) with the bivalent (quadrivalent) vaccine is predicted to reduce the cumulative incidence of anogenital warts (AGWs) by 0.0% (72.1%), diagnosed cervical intraepithelial neoplasia lesions 2 and 3 (CIN2 and -3) by 51.0% (46.1%), and cervical squamous cell carcinoma (SCC) by 31.9% (30.5%), over 70 years. Changing from a bivalent (quadrivalent) to a nonavalent vaccine is predicted to reduce the cumulative number of AGW episodes by an additional 66.7% (0.0%), CIN2 and -3 episodes by an additional 9.3% (12.5%), and SCC cases by an additional 4.8% (6.6%) over 70 years. Differences in predicted population-level effectiveness between the vaccines were most sensitive to duration of protection and the time horizon of analysis. The vaccines produced similar effectiveness at preventing noncervical HPV-related cancers. CONCLUSIONS The bivalent vaccine is expected to be slightly more effective at preventing CIN2 and -3 and SCC in the longer term, whereas the quadrivalent vaccine is expected to substantially reduce AGW cases shortly after the start of vaccination programs. Switching to a nonavalent vaccine has the potential to further reduce precancerous lesions and cervical cancer.

Understanding differences in predictions of HPV vaccine effectiveness: a comparative model-based analysis.

Mathematical models of HPV vaccine effectiveness and cost-effectiveness have produced conflicting results. The aim of this study was to use mathematical models to compare and isolate the impact of the assumptions most commonly made when modeling the effectiveness of HPV vaccines. Our results clearly show that differences in how we model natural immunity, herd immunity, partnership duration, HPV types, and waning of vaccine protection lead to important differences in the predicted effectiveness of HPV vaccines. These results are important and useful to assist modelers/health economists in choosing the appropriate level of complexity to include in their models, provide epidemiologists with insight on key data necessary to increase the robustness of model predictions, and help decision makers better understand the reasons underlying conflicting results from HPV models.

Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection

Background: A vaccine against human papillomavirus (HPV) types 6, 11, 16 and 18 is now licensed for use in Canada and many other countries. We sought to estimate the number needed to vaccinate to prevent HPV-related diseases and death. Methods: A cohort model of the natural history of HPV infection was developed. Model simulations were based on 209 different parameter sets that reproduced Canadian HPV type-specific data for infection, cervical intraepithelial neoplasia, cervical cancer and genital warts. The number needed to vaccinate was calculated as the number of women who would need to be vaccinated to prevent an HPV-related event during their lifetime. Results: Among 12-year-old girls, we estimated that the number needed to vaccinate to prevent an episode of genital warts would be 8 (80% credibility interval [CrI] 5–15) and a case of cervical cancer 324 (80% CrI 195–757). These estimates were based on the assumption that the vaccine procures lifelong protection and that its efficacy is 95%. If vaccine protection is assumed to wane at 3% per year, the predicted number needed to vaccinate would increase to 14 (80% CrI 6–18) and 9080 (80% CrI 1040–does not prevent), respectively. The latter number would be greatly reduced with the addition of a booster dose, to 480 (80% CrI 254–1572). Interpretation: Our model predictions suggest that vaccination with the currently available HPV vaccine may significantly reduce the incidence of genital warts, cervical intraepithelial neoplasia and cervical cancer. However, the benefits (particularly in terms of cervical cancer reduction) are highly dependent on the duration of vaccine protection, on which evidence is currently limited.

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: A transmission-dynamic modeling study

BACKGROUND The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions. METHODS We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs (

The impact of differential uptake of HPV vaccine by sexual risks on health inequalities: a model-based analysis.

CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations. RESULTS Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage,

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population- Level Effectiveness?

95/dose), using the quadrivalent and bivalent vaccines is estimated to cost

Contents Vol. 12, 2009

15,528 [12,056;19,140] and

The potential cost-effectiveness of prophylactic human papillomavirus vaccines in Canada

20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is