How can China achieve WHO’s 2030 targets for eliminating cervical cancer?
BMJ 2024; 386 doi: https://doi.org/10.1136/bmj-2023-078641 (Published 30 August 2024) Cite this as: BMJ 2024;386:e078641Read the collection: Promoting women's health in China
- 1Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- 2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynaecological Diseases, State Key Laboratory of Common Mechanism Research for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- 3Department of Global Health, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Correspondence to: L Zhu zhu_julie{at}vip.sina.com
As a preventable disease, cervical cancer remains a major global public health problem, ranking as the fourth most common cause of cancer in women worldwide in 2022.1 In 2018, the World Health Organization’s director general called for all nations to mobilise resources to eliminate cervical cancer (reduce incidence below 4/100 000 women years). In November 2020, WHO launched the global strategy to accelerate the elimination of cervical cancer.2 The strategy includes achieving 90% coverage of the human papillomavirus (HPV) vaccine among girls by the age of 15 years, 70% coverage of twice lifetime cervical screening with a high performance test by age 45 years, and 90% delivery of treatment needed for cervical cancer and precancer by 2030. After the initial enthusiasm, the challenges of meeting these targets in all settings have become clear. Moreover, the effect of the covid-19 pandemic on delivery of health services delayed the implementation of cervical cancer elimination for three years. How to accelerate the cervical cancer elimination goal in the post-pandemic era is a pressing global concern.
China has made considerable efforts in cervical cancer prevention since the late 1990s (fig 1). In 2023, the central government put forward the Action Plan for Accelerating Elimination of Cervical Cancer (2023-2030).3 As part of the Healthy China Initiative, a nationwide campaign launched by authorities in 2019 to promote overall national health, several pilot healthy cities have initiated demonstration programmes for eliminating cervical cancer, including health education and local government funded HPV vaccination for girls aged 9 to 14 years. By the end of 2022, 8 of 11 pilot cities (including Ordos, Chengdu, and Jinan) with free or financial compensation policies for HPV vaccination had achieved vaccination coverage of 80% or higher among targeted girls.4
However, great challenges remain to achieve the elimination goal for the whole country, considering its vast size, large population, and disequilibrium in health and economic development. For regions or populations with low health resources (including underprivileged groups in both urban and rural areas), imposing elimination targets without appropriately coordinated management and government support could lead to local confusion or absence of motivation. Such outcomes could worsen health inequities within the country and impede cervical cancer elimination.
China’s cancer burden is severe. The “two cancers” (cervical and breast cancer) screening programme is the only nationwide government led cancer screening initiative, with other cancer screening programmes still in the small scale exploration stage. Although including HPV vaccination in the national immunisation programme and scaling up screening requires substantial financial investment in the short term, in the longer term an effective elimination programme could be cost saving because of reductions in expenditure on treating invasive cervical cancer.5 Accelerating the elimination of cervical cancer can free up financial resources earlier for tackling other cancers, and serve as a model for broader cancer prevention efforts in China.
Expanding HPV vaccination
HPV vaccination is not only an efficient measure to prevent cervical cancer but also an important supplemental strategy to enhance health equity in low resource settings, where access and affordability of screening and treatment services are usually poor. To date, 139 countries out of 194 have introduced HPV vaccination into their national immunisation programmes, but China is not one of them.6 Leaving HPV vaccination uptake purely to market forces decreases vaccine accessibility for women in low resource settings. According to a recent study, the coverage of all marketed vaccines not included in the national immunisation programme was 41.2% among local urban children (excluding urban children in migrant families) but only 5.7% among children whose migrant parents left them behind in rural areas.7 The striking disparity in vaccination uptake exacerbates existing health inequities.
The first HPV vaccine was licensed by China’s National Medical Products Administration in 2016, 10 years after the first global licensing. With the recent licensing of two domestic bivalent HPV vaccines, there are now five types of HPV vaccines available in the country: Cervarix, Gardasil, Gardasil 9, Cecolin, and Walrinvax. The domestic bivalent HPV vaccines are highly effective against high grade genital lesions and persistent infection related to HPV16 and HPV18.8 Moreover, they are cheaper than imported vaccines. The cost of domestic HPV vaccines was about $46 (£36; €43) per dose in 2023, compared with $82.86-$185.43 per dose for imported vaccines. Notably, tender prices in government funded HPV vaccination programmes have decreased to $9.39-$21.79 per dose for domestic bivalent vaccines.
Both domestic vaccine companies have also recently announced an annual vaccine production capacity of 30 million doses each. According to the latest census data there are around 7.5 million 14 year old girls in China,9 representing a basic demand of 13.5 million vaccine doses a year to achieve a 90% coverage in the two dose schedule. Moreover, new generation vaccine candidates are under development. As such, the vaccine supply should meet the demand of the national immunisation programme in the foreseeable future. The effective and affordable vaccine resources from China will also provide high quality vaccine options for other middle and low income countries that have not yet included HPV vaccines in their immunisation programmes.
China has a relatively comprehensive vaccine service infrastructure, encompassing well developed information systems, robust hardware facilities for cold chain transportation, and adequately matched human resources. It therefore has the flexibility to include a new vaccine for nationwide immunisation. Moreover, the covid-19 pandemic pushed the country to enhance its capacity in vaccine delivery and increased the public awareness and acceptability of vaccination. Nevertheless, several studies indicate that rural areas, which bear a heavier burden of cervical cancer, have lower levels of awareness regarding HPV infection and vaccination.10 This may affect the implementation of comprehensive cervical cancer prevention and control strategies in these areas. To address this issue, China has promoted interventions such as HPV awareness day events and group educational interventions in recent years.
Increased availability of domestic advances and improved awareness pave the way for achieving the 90% HPV vaccination coverage goal, even for low health resource regions. However, inclusion of HPV vaccination in the national immunisation programme is a long term plan. The current high price of HPV vaccines would create a large annual financial burden and challenge the financial sustainability of the programme. China needs to negotiate a reasonable and affordable price for bulk purchase and to establish a sustainability mechanism involving multiple stakeholders, including governments at different levels, HPV vaccine manufacturers, and non-governmental organisations. Moreover, policy incentives and financial support are needed for low health resource settings.
Emerging global evidence from immunogenicity trials, efficacy trials, and post-licensing observational studies has indicated that one dose of vaccine could be as effective as two or three doses in protecting against infection and clinical endpoints over more than 10 years.11 In 2022, a WHO position paper recommended one or two doses in females aged 9-20 years,12 which could expedite progress towards scaling up HPV vaccination in settings with limited supply and budget. Adopting a one dose schedule in China would reduce the costs and free up doses to allow more rapid scale-up of vaccination.13 However, population based evidence on the effectiveness of the one dose schedule is lacking in the country. More robust evidence is required before national approval of a one dose schedule.
Public health authorities have a moral obligation to assess prospective immunisation initiatives and deliver essential basic health services for the overall wellbeing of the nation. Besides negotiating lower prices and exploring options tailored to low resource settings, the government must bolster political determination to implement the HPV immunisation programme. This could ensure full resource integration, directing policy makers towards more effective and efficient actions, and equally benefiting all eligible girls regardless of their economic status.
Cervical cancer screening coverage
Cervical screening aims to find and treat precancerous cervical cell changes to prevent cervical cancer from developing. The National Cervical Cancer Screening Programme in Rural Areas was launched in 2009 to provide free cervical examinations for rural women.14 Since then, the coverage of cervical cancer screening has gradually expanded, with an estimated 85 million examinations up to 2018. However, the number of rural women participating in screening during 2016-18 accounted for only 26% of the rural women of appropriate age in the same period.15 Screening coverage was also low at the national level (both urban and rural areas), with the lifetime screening coverage for women aged 35-64 years in China was reported to be 36.8% in 2018-19.16 This is substantially below WHO’s goal of 70% coverage with at least two lifetime screenings.
The Chinese government integrated cervical cancer screening into the basic public health services in 2019. However, this created challenges for budget allocation. Although the per capita fiscal subsidy for basic public health services increased from ¥69 (£7.50; €8.90; $9.50) in 2019 to ¥89 in 2023, it is still hard to cover the 19 basic public health service projects. Without specific allocations from local governments, it is challenging to achieve improvements in screening coverage and screening quality, especially in low health resource settings. A stepwise approach assigning pragmatic, time bound, local targets might be useful to encourage developed regions to innovate in the resource allocation and financing of cervical cancer screening. Alternatively, the central government could adjust the proportion of financial support to low resource regions according to the local economic situation.
Applying new technology
China needs to improve not only the coverage but also the screening technology. In 2020, WHO recommended the HPV nucleic acid test as the primary screening tool for cervical cancer because of its high sensitivity and performance. However, the most widely used screening tools in China are the Pap smear test and visual inspection with acetic acid or Lugol iodine (82.28% and 13.75%, respectively, of the total screened population in 2009-18).15 Because of the complicated approval process and other restrictions, only two of more than 100 HPV nucleic acid test products were approved by the National Medical Products Administration for primary cervical cancer screening by 2023.
Another major barrier to cervical cancer screening is the lack of qualified staff. According to the 2019 national pathology quality report, 48% of the pathology departments had two or fewer pathologists.17 As a result of insufficient colposcopy and histopathology capacity, some regions mainly rely on specialist hospitals or third party agencies for their screening tests and pathological diagnosis. Greater use of simple screening approaches such as self-sampling testing, point-of-care screening, and artificial intelligence (AI) based diagnostic technology could help overcome capacity problems and improve screening efficiency.
Appropriate screening strategy
Taking into account the unbalanced economic development of countries around the world, WHO recommends a minimum of two lifetime screens with a high performance HPV test, one by age 35 and another by age 45 years.2 The incidence of cervical cancer in China significantly increases with age and peaks at 50-54 years.18 The national cervical cancer screening protocol issued in 2021 recommends screening every three years with a cytology test or five years with HPV test for women aged 35-64 years, which fits well with the age trend of cervical cancer in China.19 However, use of the traditional cytology test in national screening programmes is not sustainable because of its low sensitivity and high dependence on the medical workforce and diagnostic services. There were more than 296 million women aged 35-64 in China in 2020, and a cytological examination every three years for these women would require a lot of labour and resources. China should therefore accelerate the switch from cytology testing to HPV testing to save screening costs and improve screening efficiency.
In most regions of China, a five yearly HPV test should be feasible and appropriate. However, it could create financial and workforce challenges in low resource settings. A Chinese study based on the cervical cancer screening cohort among Chinese women showed that the probability of transitioning from normal cells to CIN2 or CIN3+ over 10 years was ≤0.01.20 Given this extremely low transition probability, extending the screening interval (to 10 years or more) based on health service capacity and health budget assessments is also acceptable in settings with extremely low health resources.
Effective integration of information and data
Currently, China lacks an information system to effectively manage screening invitations and follow-up, which is critical to improving screening compliance. Cervical cancer screening data are derived from screening programmes organised by governments and opportunistic screening in hospitals or medical examination centres, and the collection and reporting of screening data also vary by institution type. By the end of 2022, China had more than 36 000 hospitals, 970 000 primary care institutions, and 3000 maternal and child health institutions. The lack of a standardised data collection platform poses a major challenge to the management of screening information from multiple sources and could lead to overscreening, which wastes health resources and results in unnecessary diagnosis and treatment because of false positive results. Therefore, there is an urgent need to establish an information sharing network for cervical cancer screening to track and monitor screening, online follow-up, and referral appointments.
Optimising linkage between screening and treatment
WHO recommends that anyone who tests positive for HPV DNA on screening should be treated without histopathological confirmation.21 However, Chinese guidelines still require histopathological confirmation before treatment. Limited diagnostic resources and lack of easy-to-use screening resources have resulted in poor treatment coverage in low resource areas. A survey reported that almost all hospitals carrying out cervical cancer screening could provide colposcopy examination, but only 40% of rural clinics were able to do pathology diagnosis.22
An alternative approach using well established electronic colposcopy technologies has been proposed in China. This approach involves immediate thermocoagulation to treat suspected high grade lesions identified during colposcopy, which is performed concurrently with biopsy. Colposcopy and thermal ablation have been shown to be effective in one large scale study in rural China.23 A “screen and treat” approach with a self-sampling HPV test linked to thermal ablation was shown to be the most cost effective approach for cervical cancer prevention in China.24 In addition, it is critical to develop simpler and more suitable technologies such as therapeutic HPV vaccines that can be easily used in primary healthcare facilities.
Recommendations
If China is to reach WHO’s target’s for cervical cancer screening and elimination it will need to adopt approaches that are adapted to local settings. The most effective measures to ensure equal and accessible healthcare services for eligible women are adding HPV vaccination to the national immunisation programme, encouraging developed regions to innovate in the resource allocation and financing of cervical cancer screening, and providing more central financial support to low resource regions (table 1).
A one dose vaccination schedule or screening with extended interval might be helpful in the transition period. However, more evidence is required to carefully evaluate the trade-offs. Moreover, it is also crucial to establish an efficient mechanism to incorporate evidence into policy decisions.
Robust policies are essential to foster technological breakthroughs. Streamlining evaluation processes, optimising systems, and expediting approvals for cutting edge innovations, including HPV therapeutic vaccines, point-of-care tests, and AI assisted screening, diagnosis, and treatment technologies, will significantly bolster China’s ability to control cervical cancer.
Achieving cervical cancer elimination demands the engagement of diverse stakeholders. Capacity building is essential not only in the health service sector but also in community engagement and the development of information platforms. Bolstering the government’s moral and political commitment to conduct national interventions is key for adequate resource mobilisation, effective actions, and the expedited elimination of cervical cancer throughout China.
Key messages
Five years after the launch of the cervical cancer elimination initiative, China still faces implementation challenges
Accelerating the inclusion of the HPV vaccine in the national immunisation programme is essential, prioritising areas with low health resources to reduce health inequities
Meeting the screening target requires greater use of HPV tests, locally appropriate screening strategies, expanded population coverage, and a comprehensive information platform
Accelerating approval process of regulatory authorities, developing tailored strategies for local settings, fostering collaborative platforms, and enhancing capacity building are recommended
Additionally, strong political will is essential to meet the established goal
Acknowledgments
We thank Tingting You, Huan Yang, and Huijiao Yan for help with the literature review, data preparation, and analysis, and Partha Basu for constructive comments and insightful discussions. We acknowledge support from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-004), Bill and Melinda Gates Foundation (INV-031449), and National High Level Hospital Clinical Research Funding (2022-PUMCH-D-003).
Footnotes
Contributors and sources: FZ’s research focuses on cervical cancer comprehensive prevention including screening, HPV vaccination, and health economic evaluation. YQ specialises in public health and population medicine research. LZ has been engaged in clinical and scientific research in difficult critical diseases and rare diseases in obstetrics and gynaecology for more than 30 years. JL is a leading expert in obstetrics and gynaecology in China, with extensive clinical experience and comprehensive knowledge. All authors contributed to writing and revising the article. FZ and LZ contributed equally and are the guarantors.
Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: YLQ and FHZ have received grants through their institution from GlaxoSmithKline Biologicals, Merck and Co, and Xiamen Innovax Biotech Co to undertake clinical trials on the HPV vaccine.
Provenance and peer review: Commissioned; externally peer reviewed.
This article is part of a collection proposed by the Peking University, led by Jie Qiao. Open access fees were funded by individual institutions. The BMJ commissioned, peer reviewed, edited, and made the decision to publish. Jin-Ling Tang and Jocalyn Clark were the lead editors for The BMJ.
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