Cost-effectiveness of single-dose versus two-dose HPV vaccination: a Markov cohort modelling analysis of a Kenya-India LMIC composite.
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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.