ArticleFrontiers in public health2026
Cost-effectiveness of single-dose versus two-dose HPV vaccination: a Markov cohort modelling analysis of a Kenya-India LMIC composite.
Article in Frontiers in public health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Cervical cancer imposes a disproportionate burden in low- and middle-income countries (LMICs), where second-dose dropout substantially limits the real-world effectiveness of two-dose HPV vaccination programmes. Single-dose schedules eliminate dropout but provide shorter-duration protection. Whether single-dose vaccination is economically preferred to two-dose vaccination, and under what conditions the two strategies yield divergent recommendations depending on the health outcome metric used, has received limited attention in published cost-effectiveness analyses, particularly for the direct head-to-head schedule comparison. Methods: We developed a static Markov cohort model, assessed for face validity against observed incidence data, tracking 100,000 girls aged 9 years through a lifetime horizon (to age 99) within an LMIC composite derived from Kenya (low-income) and India (lower-middle-income). Three strategies were compared: no vaccination (reference), 1-dose HPV vaccination (efficacy 87% against HPV 16/18-attributable CIN2+; 20-year base-case protection duration), and 2-dose vaccination (efficacy 93%; lifetime protection). Programme coverage was 49% for both strategies; a 15% second-dose dropout rate reduced 2-dose effective coverage to 41.7%. Costs (2024 USD), disability-adjusted life years (DALYs) averted, and incremental cost-effectiveness ratios (ICERs) were estimated from a healthcare payer perspective with 3% annual discounting, within a static direct-effect framework that does not capture herd immunity. Willingness-to-pay thresholds of USD 200/DALY (low-income) and USD 500/DALY (lower-middle-income) were applied from Disease Control Priorities, 3rd edition. Uncertainty was characterised through 10,000-simulation probabilistic sensitivity analysis (PSA) and pre-specified scenario analyses examining second-dose dropout rates from 5 to 45% and 1-dose protection durations of 10 years, 20 years (base-case), and lifetime. Results: Both strategies were dominant (cost-saving and more effective) versus no vaccination. Per 100,000 girls, 1-dose prevented 64 invasive cervical cancer (ICC) cases and 77 deaths, averting 5,545 DALYs with a net cost saving of USD 1,233,242 (ICER: -USD 222/DALY). Two-dose prevented more cases (87) and deaths (95) but, under the base-case 20-year protection assumption, averted fewer DALYs (5,149) and saved less (USD 980,690). This divergence reflects the age-concentration of 1-dose protection in women aged 15-29 years (86.4 DALYs per averted case vs. 59.2 for 2-dose) and is structurally dependent on the 20-year protection duration assumption; at lifetime protection, this DALY efficiency difference diminishes. In PSA, 1-dose was dominant in 99.3% of simulations (mean ICER: -USD 195/DALY; 95% credible interval [CrI]: -USD 315 to -USD 64) and cost-effective at both thresholds in 100% of simulations. Two-dose was dominant in 91.8% of simulations (mean ICER: -USD 133/DALY; 95% CrI: -USD 284 to +USD 136). The 1-dose ICER was invariant to second-dose dropout rate; the 2-dose ICER deteriorated from -USD 141/DALY at 5% dropout to -USD 105/DALY at 45% dropout. Conclusion: The finding that the single-dose strategy achieves greater DALY efficiency per dollar is structurally dependent on the base-case assumption of 20-year single-dose protection duration and should not be interpreted as a general empirical finding. Under this specific assumption, elimination of second-dose dropout raised effective coverage from 41.7 to 49.0% and concentrated protection in women aged 15-29 where each averted case contributes more years of life lost. Sensitivity analyses show this DALY efficiency advantage narrows or reverses if single-dose protection is shorter (10 years) or extends to lifetime. Across all scenarios examined, the two-dose strategy prevented more absolute cancer cases and deaths than single-dose. These are scenario-specific, exploratory findings generated within a Kenya-India composite under a static direct-effect framework; national programme decisions should incorporate country-specific dropout rates, emerging long-term evidence on single-dose protection duration, locally applicable outcome metrics, and country-calibrated modelling before drawing policy conclusions.
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