STI journal issues of nearly a decade ago, when HPV vaccination was a relatively new thing, hosted a discussion on the issue of which vaccine to choose. The choice at that time, readers will remember, was between GSK’s Cervarix 2vHPV and Merck’s Gardasil 4vHPV (Morris/STIs)*.  Now, the introduction of a third alternative, Gardasil (9vHPV), seems to have fuelled a similar burst of activity amongst mathematical modellers – at least in the US, where the new vaccine was licensed in 2014.

Gardasil 9vHPV elicits immunity to nine oncogenic (i.e. associated with cancer) serotypes – i.e. five more serotypes than Gardasil 4vHPV, and seven more than Cervatrix 2vHPV.  The nonavalent vaccine (9vHPV) is expected to extend protection from >66% to 80% of cervical cancers.  It will also, it should not be forgotten, have some benefit in preventing HPV-related oropharygneal cancers (Field and Lechner/STIs).  However, Gardasil 9vHPV is approximately $13 per dose more expensive than Gardasil 4vHPV, and $18 more expensive than Cervatrix 2vHPV.  In 2015 the US Centers for Disease Control and Prevention (CDC) recommended vaccination with any of the three alternatives for females aged 9-26yrs, and with 4vHPV or 9vHPV for males aged 11-21yrs.

Once again, then, the question of the relative cost-effectiveness of HPV vaccines raises its head – this time in the US, and in connection with a possible switch from 4vHPV and 2vHPV to 9HPV as the vaccine of choice. Mathematical modellers in the US have risen to the challenge in at least two recent studies.  Brisson & Markowitz conclude that making the switch would be cost-effective ‘under most scenarios’ (Chesson & Saraiya/STIs; Brisson & Markowitz).  Now, Durham and Galvani (D&G), in another US modelling study, have reached the same conclusion.  Not content, however, with a response for current levels of vaccination coverage, they also consider the impact on cost-effectiveness of raising national coverage with 9vHPV to higher levels.  This requires them to take into account the effect of herd-immunity, which ensures that returns on investment diminish to the extent that higher levels of coverage have already been achieved.  They also consider the relative cost-effectiveness of distributing the investment in 9vHPV vaccination in such a way as to bring up the vaccination levels in states where it is low (e.g. Arkansas, Missisipi, Missouri, Kansas) towards the levels already achieved in other states (e.g. Illinois, Montana, N. Carolina, Washington DC), as against that of an even distribution.  (At present, state vaccination rates vary between 20-57% for females, and between 9-43% for males – though inter-state migration rates are such that 29-84% of the long-term health benefits of vaccination will be realized by beyond the boundaries of the state where vaccination took place).

The findings of the study are as follows.  9vHPV is cost-effective – as compared with the alternatives – at any level of coverage.  Comprehensively switching to 9vHPV would yield the same benefit as raising levels of coverage with existing vaccines across the population of the US by 11%.  Second, assuming a comprehensive switch to 9vHPV: a national increase in coverage of 10% would show an incremental cost-effectiveness ratio (ICER) corresponding to a willingness to pay (WTP) of $40,000 per QALY, and increases of 20%, or 40%, ICERs equivalent to WTPs of $53,000 and $106,000, respectively.  Finally, the figure of $40,000 WPT per QALY given above represents only an average, since, in practice, the cost-benefit of an increase of 10% in coverage would differ widely between states with low current levels of coverage, like Arkansas, where the cost-benefit would be around $13,500, and states with high levels, like California, where it would be around $56,400. The authors therefore advocate focussing the investment needed to achieve increases in coverage on states that currently have low levels of coverage.

• a previous version of this blog mistakenly mistakenly gave the names of the manufacturers of Gardasil and Cervarix as GSK and Merck respectively.  The mistake has recently been brought to our attention, and the manufacturers as given in the emended blog (23.6.16) are the correct ones. (Blogmaster)