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Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model

BMJ 2011; 343 doi: (Published 27 September 2011) Cite this as: BMJ 2011;343:d5775
  1. Mark Jit, mathematical modeller1,
  2. Ruth Chapman, mathematical modeller1,
  3. Owain Hughes, clinical research fellow2,
  4. Yoon Hong Choi, mathematical modeller1
  1. 1Health Protection Agency, London NW9 6BT, UK
  2. 2Institute of Child Health, London WC1N 1EH
  1. Correspondence to: M Jit mark.jit{at}
  • Accepted 26 August 2011


Objectives To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity.

Design A model of HPV transmission and disease previously used to inform UK vaccination policy, updated with recent evidence and expanded to include scenarios where the two vaccines differ in duration of protection, cross protection, and end points prevented.

Setting United Kingdom.

Population Males and females aged 12–75 years.

Main outcome measure Incremental cost effectiveness ratios for both vaccines and additional cost per dose for the quadrivalent vaccine to be equally cost effective as the bivalent vaccine.

Results The bivalent vaccine needs to be cheaper than the quadrivalent vaccine to be equally cost effective, mainly because of its lack of protection against anogenital warts. The price difference per dose ranges from a median of £19 (interquartile range £12–£27) to £35 (£27–£44) across scenarios about vaccine duration, cross protection, and end points prevented (assuming one quality adjusted life year (QALY) is valued at £30 000 and both vaccines can prevent all types of HPV related cancers).

Conclusions The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost. The bivalent vaccine may have an advantage in preventing death due to cancer. However, considerable uncertainty remains about the differential benefit of the two vaccines.


  • We thank Sarika Desai and Colin Campbell for conducting the analyses on the costs of cancer, Sarika Desai and Sarah Woodhall for providing results of the burden of anogenital warts, Kate Soldan and Peter White for many helpful comments, Alan Sheridan and Joanne White for information on HPV vaccine coverage, June Boggis and Stephen Robinson for information about the cost of vaccine delivery in the UK, members of the BAPO-ENT-UK survey team (individual names listed in Hughes et al20) for information on the burden of recurrent respiratory papillomatoses, and Joakim Dillner for helpful discussions about HPV type distribution in anogenital warts.

  • Contributors: MJ designed the study; MJ, YHC, and RC carried out the computer simulations and analysis; OH carried out the survey of recurrent respiratory papillomatoses and analysed the results; RC reviewed the literature on non-cervical cancers; MJ drafted the manuscript with input from the other authors; all authors approved the final version to be published. MJ is the guarantor.

  • Funding: RC was funded by a grant from the Policy Research Programme of the Department of Health, England (reference DOH 039/0031). OH was funded by a Medical Research Council Clinical Research Training Fellowship (reference G0900348). The authors’ work was independent of the funders, who had no role in the study design, analysis of data, writing of the manuscript, or decision to submit for publication.

  • Sponsorship: None

  • All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author). OH has received unrestricted funding from Sanofi Pasteur to investigate the potential benefits of the quadrivalent L1 vaccine as therapy for recurrent respiratory papillomatoses. The other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required

  • Data sharing: No additional data available.

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