Vaccinating Women Previously Exposed to Human Papillomavirus: A Cost-Effectiveness Analysis of the Bivalent Vaccine

<div><p>Recent trials have indicated that women with prior exposure to Human papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from the HPV vaccines. However, many of the original models investigating the cost effectiveness of different vaccination strategies for the protection of cervical cancer assumed, based on the trial results at that time, that these women received no protection. We developed a deterministic, dynamic transmission model that incorporates the vaccine-induced protection of women with prior exposure to HPV. The model was used to estimate the cost effectiveness of progressively extending a vaccination programme using the bivalent vaccine to older age groups both with and without protection of women with prior exposure. We did this under a range of assumptions on the level of natural immunity. Our modelling projections indicate that including the protection of women with prior HPV exposure can have a profound effect on the cost effectiveness of vaccinating adults. The impact of this protection is inversely related to the level of natural immunity. Our results indicate that adult vaccination strategies should potentially be reassessed, and that it is important to include the protection of non-naive women previously infected with HPV in future studies. Furthermore, they also highlight the need for a more thorough investigation of this protection.</p> </div

Cost Effectiveness Acceptability Curves for Extending the Vaccination Catch-up to (A) 19 year olds and (B) 24 year olds.

<p>Different durations of vaccine induced immunity; Life (Δ), 20 years (○), 10 years (□). Thick lines represent presence of protection to HPV non-naive women and thin the absence. The results presented assumed the vaccine cost is £20 per dose (not including the cost of administering the vaccine) a 100 year time horizon and 3.5% discount rate for costs and benefits. QALY: Quality adjusted life year.</p

Long-term impact of vaccination on microfilarial load in the absence of ivermectin treatment.

<p>The green <b>(A)</b>, blue <b>(B)</b> and red <b>(C)</b> lines correspond to, respectively, a pre-control endemicity of 40%, 60%, and 80% microfilarial prevalence. The solid lines indicate the pre-control contribution of each group to the overall microfilarial load, which is the product of multiplying the microfilarial age- and sex specific profiles (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g003" target="_blank">Fig 3B</a>) times the proportion of hosts in each demographic stratum, i.e. the proportion of hosts in each age and sex group (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g002" target="_blank">Fig 2</a>). The sum total of the age- and sex-specific contributions yields the overall mean microfilarial load. The dotted lines correspond to the values after 15 years of vaccination. The shaded area illustrates the reduction in microfilarial load in those aged less than 20 years. Modelling assumptions are as follows: a vaccination programme targeting initially 1–5 year olds with continuous vaccination of one year olds after the first year of the programme; an initial prophylactic efficacy against the development of incoming worms of 50%; an initial therapeutic efficacy against skin microfilarial load of 90%; a mean duration of protective and therapeutic effects of 20 years (rate of decay = 0.05 per year) and an 80% coverage of vaccination.</p

Model-predicted proportion of bites taken on each age group.

<p>The product of multiplying the age-and sex-specific exposure profiles to blackfly bites (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g003" target="_blank">Fig 3A</a>) times the proportion of hosts in each age and sex group according to the demographic characteristics of the population (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g002" target="_blank">Fig 2</a>).</p

EPIONCHO’s underlying age- and sex-specific exposure and baseline microfilarial load profiles.

<p><b>(A)</b> The age- and sex-specific exposure profiles to blackfly bites calibrated to reproduce the observed pre-control age-dependent microfilarial loads. <b>(B)</b> The age- and sex-specific microfilarial loads in African savannah settings of northern Cameroon [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.ref032" target="_blank">32</a>]. Note that the fitting was performed using the individual data, not the binned data shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g002" target="_blank">Fig 2B</a>. Note also that the legend on panel <b>(B)</b> applies to both panels <b>(A)</b> and <b>(B)</b>.</p

Long-term impact of vaccination on onchocerciasis annual transmission potential and microfilarial load in the absence of ivermectin treatment under different assumptions of initial vaccine efficacy.

<p><b>A:</b> Model assumes an initial vaccine efficacy against the development of incoming worms of 50% and against skin microfilarial load of 90%. <b>B:</b> Model assumes a higher initial vaccine efficacy against the development of incoming worms of 70% and against skin microfilarial load of 95%. Results assume mean duration of prophylactic and therapeutic effects of 20 years (rate of decay = 0.05 per year) and an 80% coverage of vaccination. Annual transmission potential (ATP): the average number of L3 larvae potentially received per person per year.</p><p>Long-term impact of vaccination on onchocerciasis annual transmission potential and microfilarial load in the absence of ivermectin treatment under different assumptions of initial vaccine efficacy.</p

Sensitivity of the long-term reduction in microfilarial load in individuals under 20 years of age to the assumed rate of decay of vaccine efficacy.

<p>The mean duration of vaccine prophylactic (against incoming L3 larvae) and therapeutic (against microfilariae) activity is 1/the rate of decay (i.e. 5, 10, 20 and 50 years). We illustrate with a pre-control endemicity of 40% microfilarial prevalence. The solid line indicates the baseline (pre-control) contribution of each group to the overall microfilarial load, which is the product of multiplying the age- and sex-specific microfilarial loads (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g003" target="_blank">Fig 3B</a>) times the proportion of the population within each corresponding demographic stratum (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g002" target="_blank">Fig 2</a>). The dotted lines correspond to these contributions after 15 years of vaccination for decreasing waning rates of the prophylactic and therapeutic effects of the vaccine; the lower the rate, the greater the reduction in microfilarial loads achieved by the vaccination programme. Other assumptions as in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g004" target="_blank">Fig 4</a>.</p

Long-term impact of vaccination on the overall contribution to onwards transmission by age groups in the host population in absence of ivermectin treatment.

<p>The green <b>(A)</b>, blue <b>(B)</b> and red <b>(C)</b> lines correspond to, respectively, a pre-control endemicity of 40%, 60%, and 80% microfilarial prevalence. The solid line indicates the baseline age-specific contribution to the annual transmission potential (ATP, no. L3/person/year). This is obtained as the product of multiplying the following factors: age- and sex-specific microfilarial loads; proportion of the population within each corresponding demographic stratum; proportion of blackfly bites taken on each demographic stratum (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g003" target="_blank">Fig 3A</a>); annual biting rate; and the constraining (negative) density-dependent processes, acting on ingested microfilariae within the blackfly vector and on vector survival, that determine L3 output. The dotted lines correspond to the age-specific contributions to the ATP after 15 years of vaccination. The shaded area illustrates the reduction in contribution to transmission by those aged less than 20 years. Modelling assumptions on the initial vaccine efficacy and vaccine duration are as in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g004" target="_blank">Fig 4</a>. The increasing contribution to ATP by older age groups is mainly due to women for whom microfilarial load and exposure to blackfly bites increases with age (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.g003" target="_blank">Fig 3</a>).</p

EPIONCHO’s underlying demography.

<p><b>(A)</b> Age distribution and <b>(B)</b> Human sex ratio parameterised for savannah settings of northern Cameroon [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.ref032" target="_blank">32</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.ref035" target="_blank">35</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.ref036" target="_blank">36</a>].</p

Endemicity categories as defined by microfilarial prevalence.

<p>Values adapted from [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003938#pntd.0003938.ref072" target="_blank">72</a>].</p><p>Endemicity categories as defined by microfilarial prevalence.</p