Abstract
Introduction
Low- and Middle-Income Countries (LMICs), burdened with a high incidence of cervical cancer, often face challenges in implementing National Immunization Programs (NIP) or Provincial Immunization Programs (PIP) of Human Papillomavirus (HPV) vaccines. In the context of limited resources, the economic evidence provided by Budget Impact Analysis (BIA) becomes crucial for the inclusion of vaccines in the NIP and PIP.
Methods
This study adopted the perspective of the Basic Medical Insurance System (BMIS) payer, took the imported and domestic bivalent HPV vaccines as the target vaccines. We estimated the effect of HPV vaccines on burden of cervical cancer in China from 2019 to 2110, assuming that there were different reimbursement rates and market substitution rates for the vaccines. This study aimed to establish a comprehensive and standardized BIA framework that can be referenced to promote HPV vaccination in LMICs. Input parameters included vaccine efficacy vs. HPV 16/18, target age group, cancer treatment cost (per episode, over lifetime), discount rate, cohort size at 9 years old and etc., which were mainly derived from public sources, published literature, and a database of field surveys on treatment costs for patients of cervical cancer in China. Main outcomes encompassed incidence and treatment costs of cervical cancer, vaccination costs.
Results
The proposed BIA framework included the target population, BIA, and uncertainty analysis across three scenarios based on origin. In the case of China, without immunization program, the average yearly spent on cervical cancer treatment throughout the country amounts to $6,736,507.32. Upon the execution of the immunization program (2019–2025), this expenditure reduced to $6,645,564.95 each year. Under Scenario 1–3, the vaccine reimbursement costs were $62,513,268.73, $44,927,307.37, and $58,916,163.27, respectively. During the period of immunization program, annual vaccination costs constituted a range of 0.05 to 1.08 parts per million relative to the current expenditure of BMIS fund and 2.68 and 14.12 parts per million relative to current balance of BMIS fund.
Conclusion
The BIA framework provided a valuable reference for policy formulation in other LMICs with a high burden of cervical cancer that have not yet included the vaccine in their NIPs.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-026-26216-8.
Keywords: Cervical cancer, HPV vaccine, Immunization program, LMICs, Budget impact analysis
Introduction
Cervical cancer is one of the most common cancers in women globally [1]. According to GLOBOCAN2020 statistics, the global number of incidence and mortality cases of cervical cancer amounted to 604,127 and 341,831, respectively, constituting 6.5% of all female cancer incidence cases and 7.7% of all female cancer mortality cases worldwide [2]. The burden of cervical cancer globally is notably pronounced in Low- and Middle-Income Countries (LMICs), where the number of incidence and mortality cases stand at 532,239 and 312,373, representing 88.10% of all female cancer incidence cases and 91.38% of all female cervical cancer mortality cases globally [2].
The World Health Organization (WHO) emphasizes that Human Papillomavirus (HPV) vaccination is a key measure for cervical cancer elimination [3]. As of November 2022, 89.83% (53/59) of High-Income Countries (HICs) have introduced the HPV vaccine into National Immunization Programs (NIP) to leverage its public health benefits. In contrast, only 55.74% (68/122) of LMICs have introduced the HPV vaccine into NIP [4].
Economic evaluations are essential for rational resource allocation and efficiency enhancement in vaccination strategies. Evaluations are divided into Cost-Effectiveness Analysis (CEA), Cost-Utility Analysis, Cost-Benefit Analysis, and other approaches for strategies (or interventions) selection and Budget Impact Analysis (BIA) for assessing financial feasibility. The former approaches prioritise comparisons of interventions or medicines, without considering the potential implications for healthcare resource affordability. BIA specifically evaluates budgetary or resource changes caused by strategies (or interventions) [5], to assist budget holders in formulating efficient budgetary programs that promote rational healthcare resource allocation, and it must be grounded in the evidence from the former that interventions are cost-effective.
Substantial evidence supports HPV vaccination as an effective cervical cancer prevention strategy. Incorporating CEA studies from 195 countries, Rosettie et al. indicates that the pooled Incremental Cost-Effectiveness Ratios highlight the cost-effectiveness of vaccine administration in regions such as South Asia, Southeast Asia, East Asia, and Sub-Saharan Africa [6]. Burger and colleagues simulated the impact of bivalent and 9-valent HPV vaccine administration on 48 Gavi-eligible LMICs and found that implementing NIP of bivalent HPV vaccination in around 50% of LMICs is cost-effective [7]. Only two studies have assessed the affordability of HPV vaccination programs, both indicating that NIP would reduce costs for budget holders [8, 9].
In 2022, China’s share of global population was approximately 18%. China reported 150,659 new cases and 55,694 fatalities attributed to cervical cancer [10]. The aforementioned statistics represented 25.32% of the overall new cases and 17.43% of the fatalities in LMICs; simultaneously, on a global scale, China contributed to 22.76% of the overall new cases and 16.96% of the fatalities attributable to cervical cancer [10]. Despite the substantial burden of cervical cancer in China, the HPV vaccine has yet to be introduced into the NIP. Multiple studies indicate that introducing the HPV vaccine in China is cost-effective [11–13]. Regarding affordability evidence, only one study has estimated the budgetary impact of introducing the 9-valent HPV vaccine into NIP on the national Basic Medical Insurance System (BMIS) [14]. This study conducted a BIA at the national level, considering only the vaccine with the highest efficacy and cost. However, this study ignored provincial socioeconomic variations that affect vaccination coverage. Moreover, the Vaccine Administration Law of the People’s Republic of China mandated in 2019 that regions may expand their immunization programs to introduce more kinds of vaccines based on local disease prevention needs [15]. Certain regions along the southeastern coast of China have initiated the Provincial-Level Immunization Program (PIP), with part of funding being covered by the local BMIS [16]. Current research, however, has not yet focused on the potential cost savings for the BMIS fund resulting from the introduction of the bivalent HPV vaccine into both the NIP and PIP.
Given resource constraints in LMICs, economic evidence from BIA regarding vaccine inclusion in NIPs and PIPs is particularly valuable. This study aims to establish a standardized BIA framework for LMICs, using China as a case study to evaluate the the inclusion of the bivalent HPV vaccination in immunization programs at both national and provincial levels.
Materials and methods
BIA framework
This study developed a BIA framework (Fig. 1) for introducing vaccines into immunization programs, following the BIA checklist developed by Carvalho et al. [5] (Additional file 1). The framework comprised the target population, BIA, and uncertainty analysis. The target population was determined using target age population statistics and epidemiology data of cervical cancer. The BIA compared the impact of the cost of NIP and PIP on BMIS fund and the treatment cost for cervical cancer before and after the implementation of NIP and PIP. The cost of NIP and PIP was determined by size of target population, coverage, BMIS enrollment and reimbursement rates. The treatment cost of cervical cancer covered by BMIS fund was estimated using consultation, diagnostic, treatment acceptance rate, BMIS enrollment and reimbursement rates. Microsoft Excel 2021 was employed in the development of the BIA model.
Fig. 1.
BIA framework for the inclusion of HPV vaccine in immunization programs. Note: The incidence and mortality in this figure referred to incidence and mortality of cervical cancer
By adopting the perspective of a medical insurance payer, this study calculated the budget impact on China’s BMIS fund over a ninety-year span (2019–2110) of introducing the HPV vaccine into the immunization program. Immunization program in China are typically financed through public fiscal allocations or BMIS fund. As a fundamental component of China’s medical insurance system, BMIS is composed of the Urban Employee Basic Medical Insurance (UEBMI) and the Urban and Rural Resident Basic Medical Insurance (URRBMI). These two schemes vary in their benefit coverage levels and reimbursement rates for medical services. From the BMIS perspective, HPV vaccination prevents cervical cancer, thereby reducing the expenditure on reimbursing cervical cancer -related costs.
The target vaccines in this study were the imported and domestic HPV bivalent vaccines, administered in a two dose-schedule. Currently available bivalent HPV vaccines in China include the imported Cervarix® (GlaxoSmithKline Biologicals) and domestic alternatives—Cecolin® (Xiamen Innovax Biotech) and Wozehui® (Walvax Biotechnology). Both vaccine types target HPV types 16/18, which are responsible for 69.1% of cervical cancer cases, and are considered therapeutically interchangeable. The market price of the imported vaccine (¥580/US$84.10 per dose) is approximately twice that of the domestic vaccine (¥329/US$47.70 per dose, ¥319/US$46.25 per dose). In China, the economic outcomes for preventing cervical cancer with these vaccines are similar. Our earlier CEA demonstrated cost-effectiveness for the implementation of bivalent imported and domestic vaccines in China and its 31 provincial-level administrative regions when the vaccination coverage is 80% [17].
Research assumptions
Within the specified timeframe (2019–2110): (1) The constancy of the HPV vaccines’ efficacy was assumed. (2) The techniques and coverage of cervical cancer screening remained unaltered. (3) The reimbursement rates of BMIS were assumed to remain consistent. (4) Upon inclusion in the cohort in 2019, individuals were in good health and had no prior record of HPV infection. (5) Population in the cohort received a complete immunization schedule within one year.
Target population
The target population was defined as a specific age cohort - girls who were 9 years old in China in 2019 (Hereinafter, “cohort size at 9 years old”). This age threshold aligns with the minimum vaccination age for bivalent HPV vaccines established by China’s National Medical Products Administration [18]. The Action Plan to Accelerate the Elimination of Cervical Cancer in China (2023–2030) proposed by the National Health Commission of the People’s Republic of China and other relevant departments, aims to initiate pilot HPV vaccine programs for eligible girls by 2025 [19]. Consequently, this study designated the implementation period of the immunization program from 2019 to 2025.
Vaccination coverage was categorized into the initial coverage in 2019 and the predicted coverage from 2020 to 2025. The data was sourced from the National Institutes for Food and Drug Control in China, comprising 168 batches of biological product release announcements [20] and the National Immunization Program Information System [21] (Additional file 2). The statistical timeframe for the former was from December 21, 2017, to April 18, 2021 (information post-April 18, 2021, lacked specific details). Detailed national and provincial coverage rates following program implementation were provided in Additional file 2.
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, market share of imported bivalent vaccines; 
, total number of doses of imported bivalent vaccines approved and issued by biological products of the China Academy of Food and Drug Administration and Research from December 21, 2017 to April 18, 2021; 
, market share of domestic bivalent vaccines; 
, total number of doses of domestic bivalent vaccines approved and issued by biological products of the China Academy of Food and Drug Administration and Research from December 21, 2017 to April 18, 2021; 
, coverage of imported bivalent vaccine at place 
in 2019; 
, coverage of bivalent vaccine at place 
in 2019; 
, coverage of domestic bivalent vaccine at place 
in 2019; 
, average annual growth rate of coverage at place 
; 
, coverage of bivalent vaccine at place 
in 2020; 
, coverage of bivalent vaccine at place 
in 2018.
BMIS enrollment and reimbursement rates
Cost of vaccination and cancer treatment were estimated using BMIS enrollment and reimbursement rates. The former was sourced from the National Bureau of Statistics in China [22]. The latter was from a Database of field surveys of Treatment Costs for Cervical Cancer patients in China (DTCCC), encompassing outpatient and inpatient expenses, insurance information, and other data for patients of cervical cancer in the western, eastern, central, and northeastern regions of China. Provincial reimbursement ratios were adjusted based on the per capita GDP in 2019 (Additional file 2).
Scenario analysis of the bivalent HPV vaccine immunization program from the perspective of BMIS
A scenario analysis was conducted based on vaccine origin (Fig. 2), with the following design: (1) The BMIS reimbursement rate for domestic vaccines remained constant at 100% across all scenarios; (2) The BMIS reimbursement rate for imported vaccines was determined based on the Real Market Price (RMP) of domestic vaccines: 50% in Scenario 1 (equal to the RMP of domestic vaccines), 25% in Scenario 2 (125% of the RMP of domestic vaccines), and 0% in Scenario 3 (200% of the RMP of domestic vaccines); (3) The market substitution rates in each scenario were determined based on the reimbursement rates: the market substitution rate for domestic vaccines remained at 0%, while for imported vaccines, it was set at 10%, 20%, and 60% in Scenarios 1, 2, and 3, respectively.
Fig. 2.
Scenario analysis of immunization program from the BMIS perspective
Reimbursement costs for immunization program and treatment of cervical cancer
The total vaccination cost per Fully Immunized Girl (FIG) was the sum of the vaccine price per FIG and vaccine delivery costs per FIG (including costs of transportation, administration, and service). The BMIS reimbursement cost for immunization program was estimated based on the number of people vaccinated and coverage of BMIS, the total vaccination cost per FIG, and the reimbursement rate for the total vaccination cost per FIG. Data sources for these parameters were provided in Table 1.
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Table 1.
BIA input parameters for bivalent HPV immunization programs in baseline analysis in three scenarios
| Parameters | Base-case value | Source | |
|---|---|---|---|
| Vaccine efficacy vs. HPV 16/18 | 100% | [25, 26] | |
| Target age group | 9 | [18] | |
| Cancer treatment cost (per episode, over lifetime) (USD) | 7547 | [27] | |
| Discount rate | 3% | [24] | |
| Proportion of cervical cancer cases that are due to HPV 16/18 | 69.10% | [23] | |
| Standardised cohort size (disc) | Additional file 2 | [28] | |
| CeCx-16/18 incidence (disc) | |||
| Cancer care costs (disc) (USD) | |||
| Cohort size at 9 years old | Additional file 2 | [29] | |
| Market share | Additional file 2 | [20] | |
| Coverage | Additional file 2 | [21] | |
| Screening Consultation rate | 90.00% | Authors’ assumption | |
| Diagnosis rate | 81.00% | [30] | |
| Treatment acceptance rate | 90.00% | [19, 31] | |
| Vaccine price per FIG (USD) | Additional file 4 | [17] | |
| Vaccine delivery cost per FIG (USD) | |||
| Reimbursement of UEBMI | Additional file 2 | DTCCC | |
| Reimbursement of URRBMI | |||
| Coverage of UEBMI | Additional file 2 | [22] | |
| Coverage of URRBMI | |||
| Current income, current expenditure, current balance and accumulated balance of BMIS fund from 2019 to 2022 (USD) | Additional file 6 | [32–35] | |
Disc discounted, FIG Fully Immunized Girl, UEBMI Urban Employee Basic Medical Insurance, URRBMI Urban and Rural Resident Basic Medical Insurance, DTCCC Database of field surveys of Treatment Costs for Cervical Cancer patients in China, BMIS Basic Medical Insurance System
, BMIS reimbursement cost of vaccination at place 
in 
at scenario
; 
, the price of imported vaccines at place 
per FIG (Full Immunized Girl); 
, the delivery cost of vaccines at place 
per FIG; 
, BMIS reimbursement rate of imported vaccine in 
at scenario
; 
, the price of domestic vaccine at place 
per FIG; 
, BMIS reimbursement rate of imported vaccine in 
at scenario
.
The number of cervical cancer cases was calculated from the number of vaccinations and annual incidence rates. Incidence rates were obtained from the International Agency for Research on Cancer HPV Information Center [23]. The cost of cervical cancer treatment before and after vaccination were calculated based on consultation, diagnosis and treatment acceptance rates. The BMIS reimbursement cost of cervical cancer treatment before and after the implementation of the immunization program was calculated by the BMIS coverage and the reimbursement rate for treatment cost of cervical cancer.
Costs and health outcomes were discounted at 3% with reference to the Chinese Guidelines for Evaluating the Economics of Vaccines [24]. Costs were converted to U.S. dollars using the 2019 exchange rate (1 USD = 6.8967 CNY).
Affordability analysis of BMIS
BMIS fund affordability referred to the fiscal sustainability of the BMIS fund after implementing immunization program. It is primarily assessed by analyzing the proportion of the program’s expenses relative to the current expenditure of the BMIS fund, as well as proportion of the program’s expenses relative to the current balance of the BMIS fund.
 |
 |
, Indicators to assess the affordability of the BMIS fund under scenario 
for year 
;
, the current expenditure of BMIS fund for year 
; 
, the current income of BMIS fund for year 
; 
, the current balance of BMIS fund for year 
.
Sensitivity analysis
The model accounted for the uncertainty of factors such as the cost of cervical cancer treatment, vaccine prices, delivery costs, discount rate, and reimbursement rates, which fluctuated over the range presented in Table 2. Tornado charts, presented in Fig. 5, showed factors that strongly affected the increments of BMIS fund and tested the model’s robustness. The central vertical line in each hurricane plot serves as a visual guide, representing the baseline result for that specific scenario. The length of each bar showed the parameter’s effect on the change in the increments. Stronger parameter effects resulted in longer bars and higher graphic positions.
Table 2.
Parameters for univariate sensitivity analysis
| Variation range | Discount rate | Vaccine price per FIG (USD) | Vaccine delivery cost per FIG (USD) | Coverage of UEBMI | Coverage of URRBMI | Reimbursement of UEBMI | Reimbursement of URRBMI | Cancer treatment cost (per episode, over lifetime) (USD) | Cohort size at 9 years old | Initial coverage (all vaccine valences, 2019) |
|---|---|---|---|---|---|---|---|---|---|---|
| Base-case value | 3% | 102.13 | 6.73 | 23.38% | 72.78% | 62.11% | 50.41% | 7,547 | 6,860,245 | 0.97% |
| Decrease in base-case value | 0% | 20% | 20% | 16% | 5% | 10% | 10% | 20% | 10% | 0% |
| Lower bound | 3% | 81.71 | 5.38 | 19.64% | 69.14% | 55.90% | 45.37% | 6,038 | 6,174,221 | 0.97% |
| Increase in base-case value | 67% | 20% | 20% | 16% | 5% | 10% | 10% | 20% | 10% | 20% |
| Upper bound | 5% | 122.56 | 8.07 | 27.22% | 76.62% | 68.32% | 55.45% | 9,056 | 7,546,270 | 1.16% |
FIG Fully Immunized Girl, UEBMI Urban Employee Basic Medical Insurance, URRBMI Urban and Rural Resident Basic Medical Insurance
Fig. 5.
Univariate sensitivity analysis of incremental BMIS fund for domestic bivalent HPV vaccine in China. Note: This figure showed the impact of changes in the main parameters on the increment of BMIS funds under the three scenarios. The dark green bar represented the magnitude of change in the outcome measure (incremental BMIS fund) from the baseline when the parameter was increased, while the light green bar represented the magnitude of change when the parameter was decreased. The currency units for all monetary values were US dollars
Results
Baseline results
Epidemiological impact of immunization program
In Scenarios 1–3, the national coverages from 2019 to 2025 were 10.76%, with municipal coverages ranging from 0.38% to 50.49%. Incidence cases of cervical cancer began to emerge in the target cohort during 2030–2040, when populations were 20–30 years of age. The incidence trend exhibited five inflection points (2034, 2039, 2044, 2049, 2054), peaked in 2055, and then generally declined from 2056 onward, with a slight uptick observed around 2060 (Fig. 3). In comparison to the pre-vaccination period, the number of cervical cancer cases decreased by 0 to 5.28% both nationally and in 31 provincial-level administrative regions (Additional file 3).
Fig. 3.
Comparison of number of cervical cancer cases before and after the implementation of NIP in China
Affordability analysis of BMIS
The reimbursement costs of BMIS for immunization program were illustrated in Fig. 4. In Scenario 1, the total cost of immunization program reimbursed by BMIS was $62,513,268.73. Scenario 2 exhibited a decreased total cost of $44,927,307.37, representing a 28.13% reduction compared to Scenario 1. For Scenario 3, the total cost was $58,916,163.27, indicating a 31.14% increase compared to Scenario 2 and a 5.75% decrease compared to Scenario 1. Detailed results for each provincial-level administrative regions were provided in Additional file 4.
Fig. 4.
Scenario analysis of NIP costs (USD) covered by BMIS. Note: This figure depicted the cost of NIP reimbursed by BMIS in three scenarios. In each scenario, the BMIS reimbursement rate for domestic vaccines remained constant at 100%; the BMIS reimbursement rate for imported vaccines were 50%, 25%, 0% in scenarios 1, 2, 3, respectively
Without immunization program, the average yearly spent on cancer treatment covered throughout the country was $6,736,507.32. Upon the execution of the immunization program, this expenditure was reduced to $6,645,564.95. Comprehensive outcomes for each provincial-level administrative region were available in Additional file 5.
The annual vaccination cost during the implementation period of the NIP accounted for 0.05 to 1.08 parts per million of current expenditure of BMIS fund and 2.68 to 14.12 parts per million of current balance of BMIS fund. The current expenditure in each scenario covered by the current balance of BMIS fund without the need for compensation through accumulated balance of BMIS fund (Table 3).
Table 3.
Affordability analysis of immunization programs covered in BMIS fund
| Indicators | 2019 | 2020 | 2021 | 2022 | |
|---|---|---|---|---|---|
|
Program expenditure/ Current expenditure of BMIS fund |
Scenario 1 | 0.0000001076 | 0.0000000767 | 0.0000000458 | 0.0000001076 |
| Scenario 2 | 0.0000000929 | 0.0000000663 | 0.0000000838 | 0.0000000929 | |
| Scenario 3 | 0.0000001601 | 0.0000001143 | 0.0000002751 | 0.0000001601 | |
|
Program expenditure/ Current balance of BMIS fund |
Scenario 1 | 0.0000006288 | 0.0000004484 | 0.0000002680 | 0.0000006288 |
| Scenario 2 | 0.0000005122 | 0.0000003655 | 0.0000004622 | 0.0000005122 | |
| Scenario 3 | 0.0000008218 | 0.0000005865 | 0.0000014119 | 0.0000008218 | |
|
Program expenditure/ Accumulated balance of BMIS fund |
Scenario 1 | 0.0000000833 | 0.0000000594 | 0.0000000355 | 0.0000000833 |
| Scenario 2 | 0.0000000620 | 0.0000000442 | 0.0000000560 | 0.0000000620 | |
| Scenario 3 | 0.0000001065 | 0.0000000760 | 0.0000001829 | 0.0000001065 | |
BMIS Basic Medical Insurance System
This table reported the share of NIP costs in current expenditure of BMIS fund, current balance of BMIS fund, and accumulated balance of BMIS fund for each scenario
Sensitivity analysis
In each scenario, the variation in BMIS fund increment was sensitive to changes in the initial coverage (all vaccine valences, 2019), cohort size at 9 years old, and vaccine price per FIG. Variations in parameters within the specified ranges did not alter the basic conclusion, indicating robustness of the basic results. The initial coverage (all vaccine valences, 2019) impacted most on the increment in Scenario 1, while vaccine price per FIG had the greatest influence on Scenarios 2 and 3 (Fig. 5).
Discussion
This study built the framework for evaluating the affordability in LMICs by introducing vaccines into immunization programs. Using China as a case study, the framework was appied to assess the affordability of BMIS fund for bivalent HPV vaccines over a 90-year period following their inclusion in the NIP and PIP. The results revealed that China and 31 provincial-level administrative regions saved BMIS fund to pay for treatment of cervical cancer after including bivalent HPV vaccination into the immunization program. Implementing the HPV vaccine immunization program would lead to a rise in the budget of BMIS fund, while expenses for treatment of cervical cancer would gradually decline, aligning with the conclusions of Zhou and Ma (2022) [14].
In resource-limited LMICs, selecting a more affordable vaccine can ensure coverage for a larger population, effectively reducing cervical cancer incidence. In countries with sufficient budgets, vaccine valences in the BIA framework can be replaced based on the local conditions. Given the relatively lower cost of bivalent HPV vaccines compared to those of the quadrivalent or 9-valent vaccines, this study selected bivalent HPV vaccines for the immunization program. In China, the domestically produced bivalent vaccines offer a substantial price advantage. This not only supports higher vaccination coverage, but also enables a more financially sensible execution of the immunization program. To further enhance the cost-saving potential for the BMIS fund, government could adopt strategies such as subsidizing vaccine manufacturers and implementing centralized procurement to lower vaccine costs.
This BIA was a multi-scenario analytical tool that aided policy decision makers in assessing the effects of various reimbursement strategies (domestic vaccines only, joint reimbursement of domestic and imported vaccines), and varying reimbursement rates of imported vaccines (50%, 25%, and 0%) on budget holders. Based on China’s national BMIS current balance from 2019 to 2022, the results indicated that the program expenses covered by the BMIS fund in all scenarios could be entirely covered by the current balance without the requirement of using cumulative balance, demonstrating strong financial feasibility. The BMIS paid the lowest cost of vaccination in Scenario 2, saving more than Scenario 3 (reimbursement of only domestic vaccine) and Scenario 1 (higher reimbursement rate for imported vaccines). This showed BMIS fund would save the most in the scenario with a 25% reimbursement rate for imported bivalent vaccines alongside full reimbursement of domestic bivalent vaccines.
Sensitivity analysis supported policymakers in conducting a thorough evaluation of the risks and consequences associated with choices. It allowed them to identify which factors had the strongest impact on outcomes. Consequently, sensitivity analysis provided a scientific foundation for the development of policies. The results of the univariate sensitivity analysis showed that vaccine price per FIG and initial coverage (all vaccine valences, 2019) affected the incremental BMIS fund to a greater extent, and the larger the value of the parameter, the larger the incremental BMIS fund. Parameter variations did not alter the fundamental conclusion, and the findings were robust.
Reducing the financial burden on HPV vaccine recipients was just one aspect of enhancing vaccine coverage. A more essential factor was cultivating vaccine recipients’ willingness and attitudes to actively vaccinate. To achieve an effective increase in coverage, multi-party collaboration was required, including measures to expand health education and public awareness campaigns, improve immunization services, and enhance the socio-cultural environment.
This research has several limitations. First, this static analytical model did not account for indirect effects like herd immunity, potentially leading to an underestimation of BMIS fund savings. Second, the growth rate of coverage throughout the immunization program was calculated as a geometric mean of the 2018–2020 data and did not account for the effect of vaccination incentives. Immunization efforts could cause non-linear increases in coverage. Thirdly, the timeframe of this study was 90 years, during which the development of medical technology may have a greater impact on the cost of cervical cancer prevention and treatment, and the reimbursement rate of BMIS for cervical cancer treatment cost may also change. However, this study considered the risk of cervical cancer and the cost of treatment for almost the entire life cycle of the study population, and chose a longer timeframe. Fourth, the immunization schedule for this study was two doses, and the WHO currently recommends a single dose of HPV vaccine for girls aged 9–14 years. The option for a single dose of the vaccine is less costly, less resource intensive and easier to administer [36]. Fifth, the sensitivity analysis in this study was univariate sensitivity analysis, and the correlation between the parameters was not considered. In the end, future studies should account for the incidence of HIV in simulations of disease burden of cervical cancer since it increases the risk of developing cervical cancer.
In conclusion, the BIA framework we developed to assess the inclusion of the HPV vaccination in immunization program provided a reference for policy evaluation and formulation in LMICs with a high burden of cervical cancer that have not yet included the vaccines in immunization program. In the case study of China, the implementation of bivalent HPV vaccines NIP and PIP in China was financially affordable for the BMIS fund. NIP and PIP would reduce the disease burden of cervical cancer and save BMIS fund for treatment of cervical cancer. Combined reimbursement of imported and domestic HPV vaccines would realize optimal savings for BMIS fund compared to reimbursement of only domestic HPV vaccines.
Supplementary Information
Acknowledgements
The authors would be grateful to Fundamental Research Funds for the Central Universities, Open Project of Think Tanks of Universities in Heilongjiang of China, Ministry of Education Humanities and Social Sciences Research Project in China.
Abbreviations
- LMICs
Low- and Middle-Income Countries
- HPV
Human Papillomavirus
- HICs
High-Income Countries
- NIP
National Immunization Program
- CEA
Cost-Effectiveness Analysis
- BIA
Budget Impact Analysis
- BMIS
Basic Medical Insurance System
- PIP
Provincial-Level Immunization Program
- UEBMI
Urban Employee Basic Medical Insurance
- URRBMI
Urban and Rural Resident Basic Medical Insurance
- DTCCC
Database of field surveys of Treatment Costs for Cervical Cancer patients in China
- RMP
Real Market Price
- CeCx-16/18 incidence
Incidence of HPV 16/18 genotypes in cervical cancer
- FIG
Fully Immunized Girl
- PRIME
Papillomavirus Rapid Interface for Modelling and Economics
Authors’ contributions
L.Z. and Y.L. designed the project and oversaw the analysis. Y.L. did the analyses for budget impact analysis and wrote the first draft of the manuscript. Y.L., R.X., P.C., B.L. and L.Z. prepared data used in study. L.Z. and X.Z. supervised the entire project and acquired funding. All coauthors provided feedback during the design and interpretation of the project. All authors read and approved the final manuscript.
Funding
Fundamental Research Funds for the Central Universities (2024-JYB-XJSJJ019); Open Project of Think Tanks of Universities in Heilongjiang of China (ZKKF2022089); and Ministry of Education Humanities and Social Sciences Research Project in China (25YJAZH247).
Data availability
Data are available on additional file 1-6.
Declarations
Ethics approval and consent to participate
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Liangru Zhou, Email: zlr1220@126.com.
Xin Zhang, Email: zhangxinzhx0801@126.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data are available on additional file 1-6.