British Medical Journal – 10 January 2015 (vol 350, issue 7990)

British Medical Journal
10 January 2015 (vol 350, issue 7990)
http://www.bmj.com/content/350/7990

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Editorials
Two or three doses of human papillomavirus vaccine?
Julia Brotherton, medical director
Author affiliations
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.g7778 (Published 07 January 2015) Cite this as: BMJ 2015;350:g7778
Switching to two doses looks feasible, but only with careful monitoring
Human papillomavirus (HPV) vaccines have the potential to prevent the considerable morbidity and mortality caused by oncogenic HPV types. In the eight years since the vaccines were first licensed, we have seen remarkable reductions in genital warts, HPV infections, and pre-cancerous cervical lesions in vaccinated populations.1 2 3 4 5 6 7 8 However, achieving high coverage with three doses of vaccine is challenging in many populations, and the cost of the vaccine has kept it out of reach for many countries. In a linked paper (doi:10.1136/bmj.g7584), Jit and colleagues explore, through modelling, the potential cost effectiveness of a two dose HPV vaccination schedule.9
Both the bivalent and quadrivalent HPV vaccines were initially registered for use as three dose courses given over six months, using the model of subunit vaccines for which multiple doses are needed to generate a sufficient immune response. However, HPV vaccines are notably immunogenic, producing very high and durable antibody responses, and the virus-like particle structure of the vaccines, with their repetitive antigen display, may be stimulating immunity that is more akin to the response generated by viral infections or live vaccines.10 …

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Research
Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model
Mark Jit, mathematical modeller and health economist12, Marc Brisson, associate professor of mathematical epidemiology and health economics345, Jean-François Laprise, mathematical modeller3, Yoon Hong Choi, mathematical modeller16
Author affiliations
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.g7584 (Published 07 January 2015) Cite this as: BMJ 2015;350:g7584
Abstract
Objective
To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose.
Design
Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years’ vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection.
Setting
United Kingdom.
Population
Males and females aged 12-74 years.
Interventions
No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years.
Main outcome measure
Costs (from the healthcare provider’s perspective), health related utilities, and incremental cost effectiveness ratios.
Results
Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years’ protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17 000, interquartile range £11 700-£25 800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom.
Conclusions
Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely monitored