Modelling the effects of quadrivalent Human Papillomavirus (HPV) vaccination in Puerto Rico

<div><p>Background</p><p>No study has estimated the potential impact of Human Papillomavirus (HPV) vaccination in Puerto Rico, a population with considerable burden of HPV-related morbidities. We evaluated the health and economic impacts of implementing a vaccination strategy for females and males in Puerto Rico, with the quadrivalent HPV (HPV4) vaccine, under different vaccination scenarios.</p><p>Methods</p><p>We adapted a mathematical model which estimates the direct and indirect health benefits and costs of HPV4 vaccination in a dynamic population. The model compared three vaccination scenarios against screening only (no-vaccination) for three doses of HPV4 vaccine among individuals aged 11–15 years in Puerto Rico: 1) 34% for females and 13% for males (34%F/13%M), 2) 50% for females and 40% for males (50%F/40%M), and 3) 80% for female and 64% for male (80%F/64%M). Data specific to Puerto Rico was used. When not available, values from the United States were used. Input data consisted of demographic, behavioral, epidemiological, screening, and economic parameters.</p><p>Results</p><p>The model predicted decreases in: 1) HPV infection prevalence for females and males, 2) cervical intraepithelial neoplasia and cervical cancer incidence for females, 3) genital warts incidence for females and males, and 4) cervical cancer deaths among females, when various vaccination program scenarios were considered. In addition, when the vaccination percentage was increased in every scenario, the reduction was greater and began earlier. The analysis also evidenced an incremental cost effectiveness ratio (ICER) of $1,964 per quality–adjusted life year gained for the 80%F/64%M uptake scenario.</p><p>Conclusions</p><p>HPV vaccine can prove its cost effectiveness and substantially reduce the burden and costs associated to various HPV-related conditions when targeted to the adequate population together with an organized HPV vaccination program.</p></div

Estimated HPV 16/18 related cervical cancer deaths among females over 100 years, by vaccination scenario.

<p>Estimated HPV 16/18 related cervical cancer deaths among females over 100 years, by vaccination scenario.</p

Estimated HPV 6/11 related incidence of genital warts among males over 100 years, by vaccination scenario.

<p>Estimated HPV 6/11 related incidence of genital warts among males over 100 years, by vaccination scenario.</p

Estimated cumulative incidence costs avoided since HPV4 vaccination program started, by vaccination scenario.

<p>Estimated cumulative incidence costs avoided since HPV4 vaccination program started, by vaccination scenario.</p

Estimated HPV 16/18 related incidence of CIN 2/3 among females over 100 years, by vaccination scenario.

<p>Estimated HPV 16/18 related incidence of CIN 2/3 among females over 100 years, by vaccination scenario.</p

Estimated HPV 6/11 related incidence of genital warts among females over 100 years, by vaccination scenario.

<p>Estimated HPV 6/11 related incidence of genital warts among females over 100 years, by vaccination scenario.</p

Expression eQTL underlying Asthma GWAS hits.

*<p>Beneath the SNP ID in column 1, the reference allele and risk allele are shown (e.g. for rs7216389, C is the reference allele and T the risk allele).</p>**<p>Moffatt et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003029#pgen.1003029-Moffatt1" target="_blank">[9]</a> reported that rs3859192 in the 17q region was associated with asthma (<i>P</i> = 1.12×10⁻¹²). SNP rs3859192 was the most significant eSNP at this locus – strongly associated with GSDMA levels (<i>P</i> = 3.55×10⁻¹⁵¹) but weakly associated with GSDMB levels (<i>P</i> = 3.86×10⁻⁵).</p>***<p>Moffatt et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003029#pgen.1003029-Moffatt1" target="_blank">[9]</a> reported that SNPs at the IL1RL1 locus were associated with asthma and the GWAS peak was located at rs3771166. The latter SNP was not a strong lung eSNP (failed to pass 10% FDR). Another SNP at the IL1RL1 locus, rs13431828, was strongly associated with asthma (Moffatt et al. <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003029#pgen.1003029-Moffatt1" target="_blank">[9]</a>, <i>P</i> = 1×10⁻¹⁰) and IL1RL1 expression level (<i>P</i> = 7.48×10⁻⁸).</p

Relative expression of <i>GSDMA</i> and <i>GSDMB</i>.

<p>Primary human airway epithelial cells in monolayer culture were analyzed for; (a) the relative abundance of mRNA for <i>GSDMA</i> and <i>GSDMB</i> (n = 7) and (b) Protein expression of <i>GSDMA</i> and <i>GSDMB</i> by Western blot normalized to expression of β-tubulin (n = 10). (c) Representative image of <i>GSDMA</i> expression in human conducting airway by immunohistochemistry, which shows expression of <i>GSDMA</i> in both basal and apical cells within the airway epithelium.</p

Lung eQTLs found on chromosome 17q21.

<p>(a) The upper panel is a region of chromosome 17q21 from the UCSC browser showing the genes located in this region. The next panel shows the results from the GABRIEL consortium <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003029#pgen.1003029-Moffatt1" target="_blank">[9]</a> (each bar represents a SNP and the y-axis shows −log₁₀<i>P</i> values for association with asthma). The following three panels show the lung eQTL results for expression levels of <i>ORMDL3</i> (blue bars), <i>GSDMB</i> (green bars), and <i>GSDMA</i> (red bars), respectively. The y-axis represents −log₁₀<i>P</i> values derived from the meta-analysis of gene expression. The black horizontal lines are drawn at <i>P</i> = 0.05. (b) Boxplots of lung gene expression levels for GSDMA according to genotype groups for SNPs rs3859192 and rs7216389 in 1,111 subjects.</p

Overall study design and analysis workflow.

<p>Overall study design and analysis workflow.</p