Informing HPV vaccine pricing for government-funded vaccination in mainland China: a modelling study

Abstract

Background: The high price of HPV vaccines remains a significant barrier to vaccine accessibility in China, hindering the country's efforts toward cervical cancer elimination and exacerbating health inequity. We aimed to inform HPV vaccine price negotiations by identifying threshold prices that ensure that a government-funded HPV vaccination programme is cost-effective or cost-saving.

Methods: We used a previously validated transmission model to estimate the health and economic impact of HPV vaccination over a 100-year time horizon from a healthcare payer perspective. Threshold analysis was conducted considering different settings (national, rural, and urban), cervical cancer screening scenarios (cytology-based or HPV DNA-based, with different paces of scale-up), vaccine types (four types available in China), vaccine schedules (two-dose or one-dose), mode of vaccination (routine vaccination with or without later switching to high-valency vaccines), willingness-to-pay thresholds, and decision-making criteria (cost-effective or cost-saving). Furthermore, we examined the budget impact of introducing nationwide vaccination at the identified threshold prices.

Findings: Using the current market price, national routine HPV vaccination with any currently available vaccine is unlikely cost-effective. Under a two-dose schedule, the prices of the four available HPV vaccine types cannot exceed $26-$36 per dose (44.1%-80.2% reduction from current market prices) depending on vaccine type to ensure the cost-effectiveness of the national programme. Adopting vaccination at threshold prices would require an annual increase of 72.18%-96.95% of the total annual National Immunization Programme (NIP) budget in China. A cost-saving routine vaccination programme requires vaccine prices of $5-$10 per dose (depending on vaccine type), producing a 21.38%-34.23% increase in the annual NIP budget. Adding the second dose is unlikely to be cost-effective compared to a one-dose schedule, with the threshold price approaching or even falling below zero. Rural pilot vaccination programmes require lower threshold prices compared with a national programme.

Interpretation: Our study could inform vaccine price negotiation and thus facilitate nationwide scale-up of current HPV vaccination pilot programmes in China. The evidence may potentially be valuable to other countries facing HPV introduction barriers due to high costs. This approach may also be adapted for other contexts that involve the introduction of a pricy vaccine.

Funding: CAMS Innovation Fund for Medical Sciences (CIFMS); Bill & Melinda Gates Foundation.

Keywords: Budget impact; Cost-effective; HPV vaccination programme; Pricing; Threshold price.

Fig. 1

Cost-effectiveness acceptability curves for nationwide routine HPV vaccination at current market prices (compared with no vaccination). The figure illustrates the probability of cost-effectiveness compared to no vaccination for nationwide routine HPV vaccination at current market prices, across various willingness-to-pay (WTP) thresholds. Panels A–D in the left display results for the two-dose schedule, while panels E–H in the right present results for the one-dose schedule. Results under HPV DNA-based screening scenarios are depicted in blue, while Liquid-based cytology-based (LBC-based) screening scenarios are shown in green. Under two screening strategies, different screening scale-up rates were set according to the year achieving 70% coverage, depicted by varying line styles in the figure. Consequently, the figure illustrates a total of six screening scenarios, each denoted by distinct abbreviations. For example, HPV 2030 represents HPV DNA-based screening reaching 70% coverage by the year 2030. These probabilities were calculated based on 500 Monte Carlo simulations. Domestic HPV-2 = domestically produced bivalent HPV vaccine (Cecolin®); Imported HPV-2 = imported bivalent HPV vaccine (Cervarix®); HPV-4 = quadrivalent HPV vaccine (Gardasil®); HPV-9 = nonavalent HPV vaccine (Gardasil-9®); WTP = willingness-to-pay; HPV 2030 = HPV DNA-based screening reaching 70% coverage by the year 2030; HPV 2050 = HPV DNA-based screening reaching 70% coverage by the year 2050; HPV 2070 = HPV DNA-based screening reaching 70% coverage by the year 2070; LBC 2030 = LBC-based screening reaching 70% coverage by the year 2030; LBC 2050 = LBC-based screening reaching 70% coverage by the year 2050; LBC 2070 = LBC-based screening reaching 70% coverage by the year 2070.

Fig. 2

Threshold vaccine price per dose for routine vaccination by setting, screening scenario, and vaccine type (one-dose schedule). Threshold vaccine prices are estimated across various settings (national, urban, and rural), screening scenarios (LBC-based or HPV DNA-based, with varying rates of scale-up), and vaccine types (domestically produced HPV-2, imported HPV-2, HPV-4, and HPV-9). The threshold prices for one-dose HPV vaccination (vs no vaccination) as well as the threshold prices for the second dose (vs maintaining the one-dose schedule) are included. Panels A–C display results for the cost-effective threshold prices, while panels D–F display results for the cost-saving threshold prices. The points in various colours represent the median values of Monte Carlo simulations corresponding to different screening scenarios, while error bars indicate the 80% uncertainty intervals (i.e., 10th–90th percentiles). Negative values are displayed as 0 in the figure. Domestic HPV-2 = domestically produced bivalent HPV vaccine (Cecolin®); Imported HPV-2 = imported bivalent HPV vaccine (Cervarix®); HPV-4 = quadrivalent HPV vaccine (Gardasil®); HPV-9 = nonavalent HPV vaccine (Gardasil-9®); HPV 2030 = HPV DNA-based screening reaching 70% coverage by the year 2030; HPV 2050 = HPV DNA-based screening reaching 70% coverage by the year 2050; HPV 2070 = HPV DNA-based screening reaching 70% coverage by the year 2070; LBC 2030 = LBC-based screening reaching 70% coverage by the year 2030; LBC 2050 = LBC-based screening reaching 70% coverage by the year 2050; LBC 2070 = LBC-based screening reaching 70% coverage by the year 2070.

Fig. 3

Budget impact of introducing nationwide HPV vaccination at identified threshold prices, offset by reduced cervical cancer screening and treatment costs in China. Average annual costs paid or saved over the first five years and over 100 years are represented by solid colour blocks and colour blocks with grids, respectively. Bars in green and red with negative values indicate average cost savings attributed to reductions in cervical cancer treatment, and in screening and CIN treatment costs, respectively. Bars in dark blue represent the annual HPV vaccination budget at cost-saving threshold prices. The incremental vaccination costs at cost-effective threshold prices, compared with the vaccination budget at cost-saving prices, are presented as bars in light blue. Dots of different colours denote the proportion of the budget allocated for HPV vaccination within the current National Immunization Programme (NIP) budget at varying threshold prices (red for cost-saving threshold price, yellow for cost-effective threshold price). All values are undiscounted and depicted as the median of Monte Carlo simulations, and error bars indicate the 80% uncertainty intervals. CIN = Cervical Intraepithelial Neoplasia; CC = cervical cancer; Domestic HPV-2 = domestically produced bivalent HPV vaccine (Cecolin®); Imported HPV-2 = imported bivalent HPV vaccine (Cervarix®); HPV-4 = quadrivalent HPV vaccine (Gardasil®); HPV-9 = nonavalent HPV vaccine (Gardasil-9®); HPV 2030 = HPV DNA-based screening reaching 70% coverage by the year 2030; HPV 2050 = HPV DNA-based screening reaching 70% coverage by the year 2050; HPV 2070 = HPV DNA-based screening reaching 70% coverage by the year 2070; LBC 2030 = LBC-based screening reaching 70% coverage by the year 2030; LBC 2050 = LBC-based screening reaching 70% coverage by the year 2050; LBC 2070 = LBC-based screening reaching 70% coverage by the year 2070.

Fig. 4

Average annual budget impact of HPV vaccination over first 5 years: proportion of total cervical cancer prevention budget at different threshold prices. The dark blue bars represent the average annual budget proportion allocated to HPV vaccination at cost-saving threshold prices within the annual cervical cancer prevention budget. The light blue bars represent the incremental proportion of the vaccination budget at cost-effective threshold prices compared to cost-saving threshold prices. The cervical cancer prevention budget encompasses the budget for HPV vaccination, cervical cancer screening, and treatment for cervical intraepithelial neoplasias (CINs) and cervical cancer cases. All values are undiscounted and presented as the median of Monte Carlo simulations. Domestic HPV-2 = domestically produced bivalent HPV vaccine (Cecolin®); Imported HPV-2 = imported bivalent HPV vaccine (Cervarix®); HPV-4 = quadrivalent HPV vaccine (Gardasil®); HPV-9 = nonavalent HPV vaccine (Gardasil-9®); HPV 2030 = HPV DNA-based screening reaching 70% coverage by the year 2030; HPV 2050 = HPV DNA-based screening reaching 70% coverage by the year 2050; HPV 2070 = HPV DNA-based screening reaching 70% coverage by the year 2070; LBC 2030 = LBC-based screening reaching 70% coverage by the year 2030; LBC 2050 = LBC-based screening reaching 70% coverage by the year 2050; LBC 2070 = LBC-based screening reaching 70% coverage by the year 2070.