The economic burden of HPVrelated diseases: Mainland China
3.2.
3.2.1.
3.2.1.1.
3.2.1.2.
3.2.2.
3.3.1.
Abbreviations
Abbreviation Definition
CC Cervical cancer
CIN Cervical intraepithelial neoplasia
HPV Human Papillomavirus
NIP National Immunization Program
UEBMI Urban Employee Basic Medical Insurance
at first sexual intercourse ranges between 17 and 23 years (5) Given that 82.4% of the population is aged 15 and older, a substantial portion of the Chinese population is at risk of HPV infection and, consequently, HPV-related diseases (5)
Cervical cancer (CC) is the most prevalent HPV-related cancer in China and the third most common female cancer in women aged 15 to 44 in the country. It has an incidence rate of approximately 11.3 cases per 100,000 women per year, leading to about 109,741 new CC cases being diagnosed annually in China (estimations for 2020). Moreover, CC ranks as the seventh leading cause of female cancer death in China, with a crude mortality rate of 8.37 deaths per 100,000 women per year, leading to about 59,060 death cases annually (estimations for 2020) (5)
Other HPV-related cancers in China include cancers of the oral cavity, vulva, vagina, anus, penis, and oropharynx, which are also often consequences of HPV infection After CC, the second most frequent HPV-related cancer is oral cavity cancer, with a crude incidence rate of 2.50 per 100,000 individuals for males and 1.64 for females However, it is important to note that, unlike CC, not all cases of oral cavity cancer are directly associated with HPV. A summary of the annual number of cases and deaths for cervical and other HPV-related diseases is presented in Table 1
Anal Cancer M: 2,498, W: 2,351 M: 1,331, W: 1,080
Oropharyngeal Cancer M: 4,372, W: 1,232 M: 2,385, W: 520
Oral Cavity Cancer M: 18,546, W: 11,571 M: 9,338, W: 5,447 2.2%
Laryngeal Cancer M: 25,871, W: 3,264 M: 13,471, W: 2,343 2.4% Vulvar Cancer 3,323 1,228 24.9%
Vaginal Cancer 1,640 682 78.0%
Abbreviations: HPV, Human Papilloma Virus
HPV-related diseases other than cancer include cervical intraepithelial neoplasia (CIN), which is a precursor to CC. It is graded based on the extent of abnormal cell changes and can be detected through regular screening, enabling timely intervention to prevent progression to invasive cancer. The standardized prevalence rates for CIN1, CIN2 and CIN3 and above in China were 3.1%, 1.3%, and 1.2% in 2022, respectively (7). More details regarding the differences between the rural and urban prevalences among the general population and HPVpositive women can be found on Table 2.
Table1. Estimated annual number of new cases and annual number of new deaths per cancer type in China in 2020
Table2. Age-standardized prevalence of HPV infection and CINs by areas among all women and HPV-positive women in 2012 (7)
The prevalence of genital warts is not usually found in literature. However, according to a study from 2017, the incidence rates of anogenital warts may vary from 0.18 to 1.26 per 1000 person-years, whereas the reported prevalence of anogenital warts in the general population in China was ~0.1–0.2% (8) Taking the Chinese population into account, around 1.4 million–2.8 million people have anogenital warts in the country
3.2. Socioeconomic burden of HPV-related diseases in China
HPV-related diseases are not only associated with increased mortality but also impose significant costs on individuals and society. The socioeconomic burden of these diseases was estimated using available data that we obtained from the literature. This involved extracting reported healthcare costs incurred by both the healthcare system and patients for each HPVrelated disease. Whenever possible, we also extracted societal costs, which include, for instance, productivity losses due to absenteeism or mortality, informal care costs, and productivity losses related to caregiving.
3.2.1. Healthcare costs
3.2.1.1. Cervical intraepithelial neoplasia (CIN) and cervical cancer
A study by Ding et al. explored healthcare costs related to CIN and CC in China from 2012 to 2019, estimating the lifetime costs associated with HPV-related diseases (9). The analysis included both outpatient and inpatient expenses, with a distinction made between costs incurred in the first year following diagnosis and those during subsequent follow-up years. The first-year costs refer to the initial treatment expenses upon diagnosis, while subsequent costs represent the average annual treatment expenses during follow-up care. Table 3 demonstrates the yearly treatment costs for different stages of CIN and CC, adjusted for 2024 inflation. The data show that treatment costs increase with disease severity, ranging from USD 444 (CNY 3,187) per year for CIN1 to USD 14,341 (CNY 102,959) per year for CC with
burden HPV-related diseases (CHI)
- Distant metastasis / distant 12,505
The lifetime treatment cost per person can reach up to USD 56,881 (CNY 408,354) for oropharyngeal cancer, USD 53,914 (CNY 387,051) for laryngeal cancer and USD 52,695 (CNY 378,299) for anal cancer (9). A full distribution of lifetime costs per cancer type and stage can be found in Table 6. As for CC, there is a decreasing trend in lifetime costs as the disease stage advances, which is attributed to the long-term maintenance treatment required for patients diagnosed with early-stage carcinoma in situ due to extended survival periods.
Table6. Lifetime treatment costs per case of HPV-related diseases according to disease stage in USD, adjusted to the year 2024 (9)
Disease (a)
Penile cancer (d)
-
intraepithelial neoplasia
Vulvar cancer
Anal cancer
Oral cavity cancer -
Oropharyngeal cancer
Laryngeal cancer
- In situ / localized
- Local metastasis/regional
- Distant metastasis/distant
- Weighted average
Unstaged cancer (b): 6.8%
Note: (a) Disease stages can be related to the traditional Tumour-Node-Metastasis (TNM) classification system as follows: “Local disease” corresponds to stages I and II TNM classification, i.e., localized primary tumour; “Regional disease” corresponds to stage III TNM classification system, i.e., metastasis to regional lymph nodes; “Distant disease” corresponds to stage IV TNM classification system, i.e., distant metastatic disease (b) As the costs for unstage cancer are unknown, the percentage of unstaged cancer cases were added to the portion of local disease stage to maintain a conservative estimation of the costs. (c) United States-based database. (d) As data for penile cancer was not available in the database, it was assumed to be the same as for vulvar cancer, as this is the most conservative value
Genital warts are another common HPV-related disease. Even though genital warts are less invasive than CC, they are the most frequent sexually transmitted viral infection in the world (11), which can lead to an economic burden within the broader context of HPV-related diseases. The lifetime treatment costs of genital warts per person adjusted to 2024 amounts to USD 322 (CNY 2,311), considering that the annual cost is used as the lifetime cost (9)
3.2.2. Indirect costs
Reported indirect costs associated with HPV-related diseases are almost absent in the literature on China. However, these costs can be substantial, particularly in the case of cancer, and consist primarily of productivity losses. They arise from absenteeism due to cancer treatment, premature death, and the caregiving responsibilities shouldered by family members or other caregivers. Additionally, there are emotional and psychological impacts on patients and their families, which may lead to further mental health care costs.
Only one estimation of indirect costs due to CC in China was reported. The potential burden was estimated based on the population of the Urban Employee Basic Medical Insurance (UEBMI) plan in a provincial capital in eastern China, which is a more economically advanced region. The potential years of life lost due to CC between 2010 and 2014 averaged around 27 years per case, with total indirect costs of USD 12.2 million (USD 16.1 million in 2024, CNY 115.5 million) and an average economic loss per case of USD 95,200 (USD 126,300 in 2024, CNY 906,645) (12).
A rough estimation of the indirect losses arising from premature death due to CC can be calculated by considering the indirect cost per case and the annual incidence of deaths due to CC (Table 7).
National indirect costs due to premature death
USD 7.4 billion (CNY 53.1 billion)
Based on current data and assuming a similar incidence for 2024, indirect total lifetime costs from premature death due to CC for that year were estimated at USD 7.4 billion (CNY 53.1 billion). These estimates can vary by region in China due to significant heterogeneity in health infrastructure and investments across the country. The total indirect costs are even higher when also considering short- and long-term work absence and caregiver absenteeism. Moreover, similar estimates can also be attributed to other HPV-related cancers.
The lack of reported indirect costs means that the true socioeconomic burden of HPVrelated diseases in China is likely underestimated. This can lead to insufficient resource allocation for prevention and treatment programs. Recognizing and addressing these hidden costs is crucial for a comprehensive understanding of the impact of HPV-related diseases on individuals and society, ultimately guiding more effective public health policies and interventions.
3.2.3. Total costs
A rough estimation of the total annual healthcare-related costs of various HPV-related cancers is provided in Table 8. This estimation was derived by taking into account the annual incidences of cases in 2020, as well as the percentage attribution to HPV multiplied by the respective costs which were reported in the previous section.
Notes: (a) For a more conservative estimation, the values were taken for in situ cancer that is not in the first year of treatment.
The total annual healthcare-related economic burden of CC in 2024 is approximately USD 926.2 million (CNY 6.7 billion), which is the highest of all types of HPV-related cancers The total annual healthcare-related economic burden for all other HPV-related cancers in 2024 is approximately USD 88.5 million (CNY 6.4 billion) This corresponds to a total annual healthcare-related economic burden of HPV-related cancers in 2024 of approximately USD
Table8 Estimated total annual costs per HPV-related cancer type taking
1.0 billion (CNY 7.3 billion) for all cancer cases These costs exclude indirect societal costs such as productivity losses due to absenteeism, disability, and premature mortality, as well as intangible costs, such as psychological distress and reduced quality of life, which further compound the economic impact. Table 9 provides a rough estimation of the healthcarerelated total lifetime economic burden of the newly diagnosed HPV-related cancer cases in China in 2024
Table9. Estimated total lifetime burden per HPV-related cancer type into account lifetime costs per incidence case, the number of these events, and the percentage of events attributable to HPV Cancer type
Notes: (a) Weighted average of lifetime costs of all cancer stages, considering the stage distribution for each cancer type
The healthcare-related total lifetime economic burden of the newly diagnosed CC cases in China in 2024 is approximately 2.9 billion (CNY 21.1 billion), which is considerably higher than the economic burden of other HPV-related cancers. The healthcare-related total lifetime economic burden of the newly diagnosed cases of other HPV-related cancers in China in 2024 is approximately USD 528 8 million (CNY 3.8 billion). The total healthcare-related economic lifetime burden of the newly diagnosed cases for all HPV-related cancers in China in 2024 is projected to reach USD 3.4 billion (CNY 24.7 billion), based on the most recent data Again, these costs exclude indirect societal costs such as productivity losses due to absenteeism, disability, and premature mortality, as well as intangible costs, such as psychological distress and reduced quality of life, which further compound the economic impact.
Even though genital warts are less invasive than cancer and require less expensive treatments, they still contribute significantly to the overall economic burden. Taking into account a conservative estimation of genital warts prevalence in China (1.4 million) and the annual average costs per genital warts of USD 322 (CNY 2,311), the costs of genital warts for China in 2024 are projected to amount to USD 450.8 million (CNY 3.3 billion)
3.3. Economic benefits of HPV-related preventive measures
HPV vaccines to adolescent girls (Figure 3) However, economically less developed areas unable to offer free HPV vaccinations have been overlooked. To support the HPV vaccination rollout, resources and funding should be directed to these regions.
Figure3. The number of areas providing free or subsidized HPV vaccination.
Among females aged 9 to 45, since the introduction of the HPV vaccine in China, there has been a consistent increase in the number of administered doses and vaccination coverage each year. However, despite this upward trend, by 2022, the first-dose coverage was only 10.15%, and the third-dose coverage was just 6.21% (4). Figure 4 provides an overview of the coverage rates from 2017 to 2022 on a provincial level
Different age groups also present different coverage rates in China. Considering all types of vaccine among the population aged 15 to 45, the highest coverage of the third dose of the vaccine was among females aged 25 to 29 years with 9.39% while girls aged 15 to 19 presented the lowest coverage, with only 2.21% of them reaching the third dose of the vaccine in 2022 (Figure 5). The HPV vaccine coverage for girls between 9 and 14 years varied across vaccine types. The cumulative coverage rate for this age group was 4.00% for the first
Figure 4. HPV vaccination coverage among females aged 9–45 years in China, 2017–2022 (%) (4)
the cost-effectiveness of HPV vaccines in China generally support their value, consistently identifying the cost of vaccination as a key factor influencing the overall cost-effectiveness of HPV vaccination programs. A series of studies conducted between 2011 and 2020 evaluated the impact and cost-effectiveness of HPV vaccination programs when added to existing screening programs, opportunistic vaccination programs, or implemented independently. They showed that, while HPV vaccination alone is valuable, combining it with expanded cervical cancer screening would enhance the overall impact on public health (19). The introduction of lower-cost domestic vaccines also offers significant potential for broader public vaccination programs, further improving cost-effectiveness (19)
In 2022, another evaluation of the cost-effectiveness of incorporating different HPV vaccines into immunization programs at a provincial and national level in China was conducted. Among all considered vaccines (domestic bivalent, imported bivalent, imported quadrivalent, imported 9-valent), the cost of the domestic bivalent HPV vaccine was the lowest, and the cost of the imported 9-valent HPV vaccine was the highest. At a national level, the treatment cost savings from implementing the vaccines ranged from USD 103 million (USD 126 million in 2024) for the domestic, imported bivalent and imported quadrivalent vaccines to USD 188 million (USD 231 million in 2024) for the 9-valent vaccine (20). The domestic bivalent, imported bivalent and imported quadrivalent HPV vaccines also averted a total of 12,545 CC cases and 5,109 deaths, while the 9-valent vaccine averted 28,140 cases and 11,459 deaths. It can be seen that the number of CC cases, deaths averted, and life-years saved by the imported 9-valent HPV vaccine was higher than the other vaccines. There are also provincial differences in the economics of HPV vaccination. Guangdong province, China’s most populous province, had the most prevented cases, and deaths, and saved the most life-years, followed by Shandong and Henan provinces. As there is a significant disparity in the ability to afford HPV vaccines across various provinces, a greater focus should be placed on economically disadvantaged areas to enhance vaccine accessibility.
Delaying the implementation of large-scale vaccination programs in China results in increased disease burden and net costs for the country, as well as a delay in CC elimination. As the HPV vaccine prices are high and only available on the private market, the uptake remains low. A large-scale state vaccination program could change this scenario, as the vaccines would be purchased by the government and provided to the target populations, likely increasing their uptake. If such a program had started in 2022, along with different screening scenarios such as lower vaccine prices compared to the current private market prices, around 15 million CC cases and 6 million deaths could have been averted by 2030, saving around USD27.7 billion (USD 32.1 billion in 2024) net costs (18). Additionally, it would allow China to eliminate CC by around 2060. On the other hand, delaying the vaccination by eight years would result in approximately 543,000 CC cases, 178,000 deaths and USD 4,4 billion (USD 4.7 billion in 2024)
16. Keane A, Shi JF, Simms KT, Liu YJ, Lew JB, Mazariego C, et al. Health economic evaluation of primary human papillomavirus screening in urban populations in China. Cancer Epidemiol. 2021;70:101861.
17. Ma L, Wang Y, Gao X, Dai Y, Zhang Y, Wang Z, et al. Economic evaluation of cervical cancer screening strategies in urban China. Chin J Cancer Res. 2019;31(6):974-83.
18. Gao M, Hu S, Zhao X, You T, Jit M, Liu Y, et al. Health and economic impact of delaying large-scale HPV vaccination and screening implementation on cervical cancer in China: a modelling study. Lancet Reg Health West Pac. 2023;36:100768.
19. Shi W, Cheng X, Wang H, Zang X, Chen T. Cost-effectiveness of human papillomavirus vaccine in China: a systematic review of modelling studies. BMJ Open. 2021;11(12):e052682.