Abstract / Summary
Abstract Introduction Mathematical modelling has informed the WHO cervical cancer elimination strategy, predicting elimination by 2120 through the 90-70-90 targets. However, those models did not account for the effect of HIV on cervical cancer. A 2022 modelling study found that even with those targets met, elimination would not be achieved among women living with HIV (WLHIV) without additional interventions. This study investigates therapeutic vaccine (TxV) impact and cost-effectiveness in the high-HIV burden setting of South Africa, where cervical cancer remains the leading cause of cancer deaths among women. Methods A microsimulation model, MicroCOSM-HPV, was adapted to project cervical cancer incidence and costs under four TxV implementation strategies in South Africa: mass vaccination, vaccination at screening, vaccination of HPV-positive women at screening, and vaccination of WLHIV receiving antiretroviral therapy (ART). TxV implementation assumed a two-dose schedule starting from 2030. Three efficacy scenarios (high: 90% against HPV infection/CIN1 and 50% against CIN2/3; medium: 70%/30%; low: 50%/0%) were investigated. A threshold price analysis estimated the maximum price per dose to remain cost-effective over the 2026–2080 period, using an opportunity cost of $3015 per disability-adjusted life year averted. Results Vaccination of WLHIV on ART averted 18.4% (95% UI: 16.2–20.8%) of cases and was cost-effective at a maximum price of $35.2 (95% UI: $19.7–52.5) per dose (high efficacy). Vaccinating HPV-positive women at screening achieved the highest maximum price of $110.5 (95% UI: $74-171.8) (high efficacy) but averted fewer cases (5.8%, 95% UI: 4.6–7.6%). No TxV strategy reduced incidence below 4 per 100,000 women by 2120. Conclusions TxV could be cost-effective in South Africa, with the maximum price per dose ranging widely for different efficacy levels and implementation strategies. TxV delivery to WLHIV on ART and/or HPV-positive women at screening should be prioritised over mass vaccination campaigns. However, even with TxV, strengthening screening, treatment, and prophylactic vaccination delivery remains necessary to achieve elimination.