**2.1 Health economics results of adopting different HPV vaccination strategies**

Assuming that the target population for HPV vaccine in Zhejiang Province is 13-year-old eligible female children and the full-course coverage rate is 80%, custom modifications were made to the birth cohort population, the target population for vaccination, the cost of HPV vaccine, the treatment expenditure for cervical cancer, and the per capita GDP of Zhejiang Province. PRIME tools were used to calculate the health economics results of different HPV vaccine vaccination strategies (Table 1).

**2.1.1 Cost-benefit analysis**

The effectiveness of bivalent and quadrivalent HPV vaccines in preventing cervical cancer caused by HPV16/18 is comparable[16], so the number of cases of cervical cancer prevented by administering bivalent or quadrivalent HPV vaccines is the same. Based on the results obtained from the PRIME tool, we found that when 13-year-old eligible female children are vaccinated with HPV vaccines and the full-course coverage rate is 80% per year, the domestic bivalent, imported bivalent, and imported quadrivalent HPV vaccines can prevent 1273 cases of cervical cancer in the target population, and the imported ninevalent HPV vaccine can prevent 1637 cases of cervical cancer. When the discount rate is 3%, the bivalent, quadrivalent, and ninevalent HPV vaccines can reduce the treatment costs of cervical cancer by 0.24 and 0.30 billion yuan, respectively. At the same time, the net cost of using domestic bivalent, imported bivalent, imported quadrivalent, and imported ninevalent HPV vaccine vaccination strategies is 1.53, 4.33, 5.97, and 9.67 billion yuan, respectively, per year.

**2.1.2 Cost-effectiveness analysis**

"Compared to not being vaccinated, vaccinating 13-year-old girls with the HPV vaccine and achieving a coverage rate of 80% can significantly reduce the incidence of cervical cancer in the target population across all age groups. With a discount rate of 3%, the cost of reducing one case of cervical cancer using domestically produced bivalent, imported bivalent, imported quadrivalent, and imported ninevalent HPV vaccines is 333,100, 939,700, 1,297,600, and 1,636,600 yuan, respectively. On the other hand, with a discount rate of 3%, the cost of reducing one death from cervical cancer using domestically produced bivalent, imported bivalent, imported quadrivelnt, and imported ninevalent HPV vaccines is 786,500, 2,218,500, 3,063,500, and 3,863,900 yuan, respectively."

**2.1.3 Cost-utility analysis**

The output of PRIME model results showed that when the discount rate was 3%, and the full coverage rate of 13-year-old eligible female children was 80%, compared to the un-implemented HPV vaccine vaccination strategy, vaccinating with bivalent or quadrivalent HPV vaccines can save the lives of 4,130 person-years of target vaccination population due to deaths caused by cervical cancer. Vaccinating with ninevalent HPV vaccines can save the lives of 5,310 person-years. At the same time, vaccinating with bivalent or quadrivalent HPV vaccines can reduce non-DALY by 293 person-years caused by cervical cancer, and vaccinating with ninevalent HPV vaccines can reduce non-DALY by 377 person-years. The CER of the immunization programs of domestically produced bivalent, imported bivalent, imported quadrivalent, and imported ninevalent HPV vaccines are 34,700, 97,800, 135,000, and 170,300 yuan, respectively. Compared with the per capita GDP of Zhejiang Province at the same time, the ratios of ICER/per capita GDP for the immunization programs of domestically produced bivalent, imported bivalent, imported quadrivalent, and imported ninevalent HPV vaccines are 0.31, 0.87, 1.19, and 1.51, respectively. The immunization program using domestically produced bivalent HPV vaccines can make the incremental cost of saving one DALY caused by cervical cancer only 0.31 of the per capita gross domestic product, which is lower than one healthy person's annual labor production value. The immunization program using imported bivalent HPV vaccines can make the incremental cost of saving one DALY caused by cervical cancer 0.87 of the per capita gross domestic product, which is also lower than one healthy person's annual labor production value.

**2.2 Sensitivity analysis**

Considering the longer cycle of HPV vaccine administration, for different immunization regimens, this study assumes that the discount rate, vaccine cost, treatment cost, target vaccination age group, and overall vaccine coverage rate are adjusted for single factors, and performs single factor sensitivity analysis when the discount rate (1%-5%), vaccine cost (original vaccine cost ± 20%), treatment cost (original treatment cost ± 20%), target vaccination age group (12-14 years old), and overall vaccine coverage rate (70%-90%) fluctuate up and down, with other factors remaining unchanged.

When administering the domestic bivalent HPV vaccine, the ICER/per capita GDP ratio is relatively stable when a single factor is adjusted and the vaccine cost fluctuates the most, followed by the treatment cost, with the target vaccination age group and overall vaccine coverage rate having a smaller impact (Figure 1). When administering the imported bivalent HPV vaccine, when the discount rate is 5%, the ICER/per capita GDP ratio is 1.69 > 1, and the discount rate has a significant impact on the ICER/per capita GDP ratio (Figure 2). Additionally, when administering imported quadrivalent and ninevalent HPV vaccines, the ICER/per capita GDP ratio is > 1 when the discount rate, vaccine cost, treatment cost, and target vaccination age group change, and there is a clear impact (Figure 3 and 4). The ICER/per capita GDP ratio increases with the increase of the discount rate and vaccine cost and decreases with the increase of the treatment cost and target vaccination age group, with no impact on the overall vaccine coverage rate.

**2.3 Recommended solution**

The results of the economic evaluation and sensitivity analysis of the four HPV vaccine immunization schemes output by the PRIME tool show that the recommended HPV vaccine immunization scheme in Zhejiang Province is to use domestic bivalent HPV vaccine, set 13-year-old eligible female children as the target vaccination group, with a vaccination coverage rate of 90%, and the net cost required is 134 million yuan. The ICER/per capita GDP ratio is 0.23, which is the optimal choice and has high economic viability (Table 2).

Implementing the HPV vaccine according to the optimal choice, using domestic bivalent HPV vaccine, from 2023, continuously vaccinate 13-year-old eligible female children in Zhejiang Province every year. As the coverage rate of the target group continues to increase, the incidence rate of cervical cancer in the target group continues to decrease. Compared with unvaccinated HPV vaccine, regardless of 70%, 80%, or 90% coverage rate, the incidence rate of cervical cancer in the target population is significantly lower than that of the non-vaccinated population. When the coverage rate of the target population is 80%, the incidence rate of cervical cancer in the target population is below 3/100,000 in all age groups. When the coverage rate of the target population is 90%, the incidence rate of cervical cancer in the target population throughout their lifetime is below 2/100,000 in all age groups (Figure 5).