Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

Abstract

Background: Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9-13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically.

Methods: We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined.

Results: We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult vaccination coverage required is modest and may be achieved simply by removing the cost burden to vaccination.

Conclusion: We recommend that provincial healthcare programs should pay for voluntary adult vaccination for women aged 14-26. However, it should be noted that our model results are preliminary, in that we have made a number of simplifying assumptions, including a lack of age-dependency in sexual partner rates, a lack of sexual activity outside of the vaccine age-range among females and a uniform age of sexual debut; thus, further work is desired to enhance the external generalisability of our results.

Figure 1

The model. Schematic representation of the model representing flow of individuals from pre- to post-vaccination. School-aged girls may be vaccinated (C_V) or unvaccinated (C_U), depending on the proportion vaccinated (p) and the immunogenicity of the vaccine (ε). Children progress to sexually active adults at rate α. Unvaccinated adult women (A_U) can either be vaccinated (f) or become infected (I_U), with probability β_N, when they meet an infected man N . Vaccinated adult women (A_V) can also become infected (I_V), but with reduced transmissibility, due to the efficacy of the vaccine ψ. Unvaccinated men (M) become infected upon contact with infected women, with transmission probability β_M. The mortality rate of children is μ_C and the leaving rate of adults is μ.

Figure 2

Thresholds of eradication. Thresholds of eradication of targeted types for vaccination coverage levels in children versus adults. A. Threshold curve assuming 95% efficacy. Parameters are given in the Table. If no adult vaccination is undertaken, then a childhood vaccination program must cover 81% of the school-aged population for eradication of targeted types. If 20% of adults are vaccinated, then the burden of childhood vaccination reduces to 74%. However, if 50% of adults are vaccinated, then eradication of targeted types can be achieved with only 55% of children vaccinated. B. If the efficacy of the vaccine is reduced to 85%, the eradication threshold is increased, assuming all other parameters remain the same.

Figure 3

Suboptimal efficacy and immunogenicity. Suboptimal values of the efficacy or the immunogenicity lead to qualitative changes in the outcome. A. There is a critical vaccine efficacy (77% in this example), such that no amount of vaccination can eradicate targeted types of the disease if the efficacy falls below this critical value. In this case, eradication of targeted types could only occur if more than 100% of children were vaccinated, which is not possible. B. If the vaccine efficacy allows for eradication of targeted types, there is a critical vaccine immunogenicity (80% in this example), such that even 100% of childhood vaccination will not eradicate targeted types of the disease. In this case, there is a minimum level of adult vaccination coverage that is required for eradication of targeted types (18% if the immunogenicity falls to 75%), even if 100% childhood coverage levels can be achieved. Adult immunogenicity was assumed to be equal to childhood immunogenicity. All other parameters as in the Table.

Figure 4

Timecourse of eradication. Time course dynamics among a community where initial conditions are taken to be the equilibrium values of an existing infection, for a vaccine with 95% efficacy and 98% immunogenicity. A. If 65% of children are vaccinated, but no adult vaccination occurs, the prevalence in the sexually active cohort is reduced to approximately half of the previous disease burden after 150 years and remains so thereafter. B. If 65% of children and 40% of adults are vaccinated, the number of infections in the sexually active cohort continues to decline, eventually approaching zero. All other parameters as in Figure 4A.

Figure 5

Dependence on parameter variation. Sensitivity of eradication threshold on parameter variation, assuming 77% childhood vaccination. A. If the average length of sexual activity before age 26 is 9 and a half years or less, then no adults need be vaccinated. If this time increases, then the threshold also increases, but still remains below 100%, even if children begin sexual activity at age 13. B. Variation as the optimal age of vaccination varies. This rate measures the age at which adult women are vaccinated, assuming 100% of adults are vaccinated with a perfect vaccine. In this case, there is little variation in the output. C. Variation in the transmission probabilities and birth rates. These parameters are always linked, so we examine them as a single unit. Even if these parameters collectively double, eradication could still be achieved with 65% adult vaccination. D. Variation in the childhood mortality rate. The output is relatively steady, unless mortality is very high. In this (unlikely) scenario, life expectancy of 30 years (17 years after vaccination at age 13) or less would clearly obviate the need for an adult vaccination program.