Cervical cancer prevention in China: a key to cancer control

Saturday, March 9, 2019

With two powerful weapons—human papillomavirus (HPV) vaccine and screening—cervical cancer has become an important preventable cancer success story. In May, 2018, the Director-General of WHO called for action towards the elimination of cervical cancer.1 China, however, as one of the top contributors to the global burden of cervical cancer, still has a long way to go before elimination.2 Since the world’s first HPV vaccine became available in 2006, the authorities in China finally approved Cervarix (GlaxoSmithKline Biologicals SA, Rixensart, Belgium) in 2016, Gardasil 4 (Merck & Co, Inc, Kenilworth, NJ, USA) in 2017, and Gardasil 9 (Merck & Co, Inc) in 2018 in mainland China.3 Despite the government’s enormous investment in cervical cancer screening since 2009, China’s national screening system still needs substantial improvement in health service capacities; optimising screening strategies; prioritising health investment; and engaging a wide range of stakeholders. Hence, for China, the goal of cervical cancer elimination seems tantalisingly within sight yet beyond reach.

That China is now shifting its focus away from its previous pursuit of rapid economic growth towards coordinated development of a health-based economy is commendable. Healthy China 2030, a wide-sweeping declaration announced by the Chinese Government in 2016, established public health as a precondition for all future economic and social development. The review by WHO of this plan indicated that “this document is the first medium to long-term strategic plan in the health sector developed at the national level since the founding of China in 1949”.4 Recently unveiled policies and actions also signal the government’s growing commitment to investing in health. Noteworthy examples include fasttracking conditional approval of the nine-valent HPV vaccine; removing import tariffs on cancer drugs and lowering value added tax; and reforming the evaluation and approval system for drugs and medical devices to streamline the China Food and Drug Administration (CFDA) regulatory process.

The outlook seems rosy. However, several major challenges remain. Scrapping the tariffs on some anticancer drugs has not relieved much of the financial burden on patients that is a consequence of the multilayered distribution system, which benefits intermediaries rather than patients; and policies for
medical insurance reimbursement that limit patients, access to medicines if the anticancer drugs are not included in the directory of health insurance in all regions of China. Likewise, the price of the HPV vaccine, ranging from ¥1740 to ¥3954 (US$254 to $576) for three doses, is a substantial obstacle for vaccine roll-out in China. Most citizens in rural China, where the disease burden is highest, are unable to afford thousands of yuan for vaccination. Moreover, vaccine supplies are far behind in meeting the demand. So far, 7 million doses of HPV vaccines have been released to mainland China’s target market—the female population aged 9–45 years.5 Yet, even when population projections are restricted to WHO’s recommended primary target group—aged 9–14 years—there are at least 41 million girls in need of vaccination in China.

A 2013 report from China predicted that if girls aged 9–15 years are left unvaccinated, approximately 381 000 preventable cases of cervical cancer and 212 000 related deaths would occur in this cohort.6 A lack of public awareness (about 16%) and low acceptability (about 67%), particularly among parents (about 30%), are also greatly hampering the uptake of the HPV vaccine in China.7 Concern about vaccine efficacy and safety, one of the most commonly raised health issues by the Chinese public, has been exacerbated by the latest vaccine scandal of a key manufacturer fabricating records regarding rabies vaccine in China.8 Although the Chinese Government has taken corrective legal action, including a record-setting corporate fine, the erosion of public trust in the vaccine system sparked by this crisis might not easily be repaired. Consequently, the available HPV vaccine is not yet affordable, accessible, or acceptable by the majority of the female population in China, especially those in rural areas. Challenges and gaps in the roll-out of HPV vaccine in China might persist for years unless corrective action is taken.

In response to these challenges, it is imperative for high-tech enterprises to tap into their capacities for innovation to supply affordable but quality-assured health-related products. careHPV Test (QIAGEN, Shenzhen, China), which gained WHO prequalification status for cervical cancer screening in July, 2018,9 might be a successful model for the high-tech sector as an easy-to-use, accurate, and affordable test. Besides, after a 6-year clinical trial, a Chinese domestic HPV vaccine (Cecolin, Xiamen Innovax Biotech Co, Ltd, Xiamen, China) has entered the CFDA’s review process, with promising results. If successfully approved, it could considerably reduce the cost of vaccination, benefiting not only China but also other low-income and middleincome countries, and thereby advancing the prevention of cervical cancer worldwide. While committed to innovation, high-tech enterprises must be strictly compliant with standard regulations and production protocols. Meanwhile, supervision authorities should strictly adhere to the quality-control standards and inspection criteria to avoid the recurrence of vaccine scandals and any other health-related tragedies.

Policy orientation holds great potential to influence decisions about health services across many sectors. Therefore, of great importance is that the Chinese Government should exert its leadership role and integrate various social resources by encouraging closer ties between key stakeholders, including those in industry, the health-care sector, and academia. Chinese research institutes or universities should translate their scientific discoveries into clinical application and public health service, thereby boosting the number and quality of innovative products entering the health market. The ultimate success of China’s cervical cancer prevention is not only an accelerator to achieve the global goal of preventing cervical cancer but also a key to unlocking full cancer control in China.

*Fanghui Zhao, Youlin Qiao

National Cancer Center & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China (FZ, YQ); and Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China (YQ)

YQ and FZ have received grants through their institution from GlaxoSmithKline Biologicals SA, Merck & Co, Inc, and Xiamen Innovax Biotech Co, Ltd to undertake clinical trials on HPV vaccine. YQ served as the principal investigator for the Cecolin (Xiamen Innovax Biotech Co, Ltd) clinical trial and co-principal investigator for Gardasil (Merck & Co, Inc), and FZ was the clinical principal investigator for Cervarix (GlaxoSmithKline Biologicals SA). YQ and FZ have received travel grants for conferences from GlaxoSmithKline or Merck in the past few years but not any from Xiamen Innovax Biotech Co. Neither YQ nor FZ have received any royalties and do not have intellectual property, patent, or stock holdings with vaccine or drug companies.

1  WHO. WHO Director-General calls for all countries to take action to help end the suffering caused by cervical cancer. reproductivehealth/call-to-action-elimination-cervical-cancer/en/ (accessed Sept 8, 2018).

2  Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394–424.

3  Pan XF, Li R, Pan A, Larson H. Human papillomavirus vaccine approval in China: a major step forward but challenges  ahead. Lancet Infect Dis 2016; 16: 1322–23.

4  WHO. Healthy China 2030 (from vision to action). healthpromotion/conferences/9gchp/healthy- china/en/ (accessed Sept 11, 2018).

5  National Institutes for Food and Drug Control. China National Institutes for Food and Drug Control Report.           (accessed Feb 27, 2019).

6  Colombara DV, Wang SM. The impact of HPV vaccination delays in China: lessons from HBV control programs. Vaccine  2013; 31: 4057–59.

7  Zhang Y, Wang Y, Liu L, et al. Awareness and knowledge about human papillomavirus vaccination and its acceptance in  China: a meta-analysis of 58 observational studies. BMC Public Health 2016; 16: 216–40.

8  The Lancet. Vaccine scandal and confidence crisis in China. Lancet 2018; 392: 360.

9  WHO. WHO prequalification of in vitro diagnostics public report.                                                                     report_hpv/en (accessed Sept 15, 2018).