Health economic impact and cost threshold for switching from bivalent to nonavalent HPV vaccination for preadolescent girls in KwaZulu Natal, South Africa: A mathematical modeling analysis accounting for the HIV epidemic.
BACKGROUND Human papillomavirus bivalent (2vHPV) and nonavalent (9vHPV) vaccines protect against HPV types causing 70% and 90% of cervical cancers, respectively. South African guidelines recommend vaccinating girls ages 9-14 with one dose of 2vHPV. Switching recommendations to 9vHPV could avert more cervical cancer burden, but the cost-effectiveness and cost-threshold of 9vHPV in South Africa is unknown. METHODS Using a validated compartmental HPV and HIV transmission model parameterized to KwaZulu-Natal, South Africa, we simulated scenarios of 2vHPV and 9vHPV implementation over 100 years with two doses (72% coverage) and one dose (80% and 90% coverage) with lifelong or waning single-dose vaccine efficacy. We evaluated cervical cancer cases and deaths averted. We also estimated the maximum cost/dose for 9vHPV to be cost-effective using willingness-to-pay thresholds from $500/DALY averted to $3,015/DALY averted (2023 USD). We also assessed the incremental cost-effectiveness ratios (ICERs) of 9vHPV at current costs ($110/dose) compared to 2vHPV ($9.23/dose). RESULTS Single-dose 9vHPV at 80% coverage could avert 7.9% more cervical cancer cases and 6.4% more deaths than 2vHPV (lifelong efficacy). The maximum 9vHPV price to be cost-effective (lifelong efficacy, 80% coverage) ranged from $15 ($500/DALY averted threshold) to $45/dose ($3,015/DALY averted threshold). At current market costs, single-dose 9vHPV at 90% coverage exceeds commonly used cost-effective thresholds with ICERs of $10,480/DALY averted (lifelong efficacy) and $8,806/DALY averted (waning efficacy). CONCLUSION Implementing 9vHPV can result in a greater reduction in cervical cancer burden than 2vHPV, but vaccine costs need to be reduced for 9vHPV to be cost-effective in KwaZulu-Natal.