Furthermore,

two-dose girls & boys is likely to provide similar or less QALYs-gained and to be more expensive than three-dose girls-only strategy, unless the third dose gives no added value or the price for boys is substantially less than the price for girls. Hence, the key question is: how long does two-dose protection have to be in order for the third dose to be cost-ineffective among girls? Our results suggest this threshold duration of protection for two doses is about 30 years. Hence, if two doses protect for more than 30 years, then the third dose will have to be priced substantially below $85 to be cost-effective. Finally, three-dose girls & boys HPV vaccination is unlikely to be cost-effective compared to three-dose girls-only vaccination, as shown by most modelling studies, unless the cost of the vaccine is substantially reduced [49], [50], [51], [52], [53] and [54]. Our results suggest that a two-dose schedule that provides HA-1077 manufacturer protection for more than 30 years would likely prevent the majority of preventable

vaccine-type AZD6244 nmr HPV infections and diseases, which entails that the added value of the third dose would be limited. This is because, at 30 years duration of protection, two-dose vaccination would confer protection during a significant proportion of the peak years of sexual activity and HPV infection (18–35 years). Our results also indicate that two-dose girls & boys vaccination is likely dominated by a three-dose girls-only strategy, because adding two doses among boys costs twice as much as adding a third dose among girls. However, because these two strategies result in comparable QALYs-gained, the price for boys would need to be reduced by more than half (60%-90% depending on duration of below protection, and assuming cost for girls ≥$30) to make a two-dose girls & boys strategy cost-effective vs. three-dose girls-only. Two key issues must be considered when using these results for decision-making. First, the policy decisions regarding alternative HPV vaccine schedules will depend on the evaluation of risks and uncertainties related to the duration of protection of two and three doses. Policy-makers could decide that

evidence is sufficient for the implementation of two-dose girls-only vaccination based on the following observations: (i) three doses in young women 16–26 years of age has shown sustained efficacy for almost 10 years [39], (ii) two doses in girls aged 9–13 years have shown noninferior immunogenicity compared to three doses in young women aged 16–26 years [14] and (iii) our results indicate that two-dose girls-only vaccination is cost-effective if the vaccine protects for longer than 10 years. On the other hand, the duration of vaccine protection with two doses remains uncertain. Should this duration be less than 20 years, a third dose extending the duration of protection (≥5 years) would likely produce substantial additional benefits.