Free HPV vaccination in many places: why choose the bivalent seedling, is the production capacity sufficient?

Author: Wu Simin

"Free HPV vaccination for women of appropriate age" adds another province, this time Jiangsu, which has the fourth largest permanent population in the country in 2022.

"Jiangsu Disease Control" WeChat public account news on the evening of March 3 said that in order to implement the "Healthy China 22" strategy, promote the comprehensive prevention and treatment of cervical cancer, and promote the construction of a healthy Jiangsu, the Provincial Health Commission, the Provincial Department of Education, and the Provincial Women's Federation jointly held a kick-off meeting in Nanjing on March 2030 to deploy the free HPV vaccine for school-age girls in the province in 3.

Cervical cancer is the fourth largest malignant tumor affecting women's health worldwide, and it is also the second largest female malignant tumor in China. Human papillomavirus (HPV) vaccination is an effective means of preventing cervical cancer. According to the Notice on Printing and Distributing the Action Plan for Accelerating the Elimination of Cervical Cancer (1-2023) issued by the National Health Commission in January this year, by 2030, HPV vaccination services for girls of appropriate age will be promoted on a pilot basis; 2025% cervical cancer screening rate among women of appropriate age; The treatment rate of patients with cervical cancer and precancerous lesions has reached 50%.

Since the launch of the first government-led HPV free vaccination program in Ordos City three years ago, Guangdong, Hainan, Jiangxi, Fujian, Tibet and Chongqing provinces have also launched or announced that they will launch a region-wide HPV vaccine free vaccination program.

Many industry experts believe that since the launch of HPV vaccine in China, the vaccination volume has increased year by year, but there are still problems such as limited vaccination coverage, uneven distribution, and the market chasing high-priced vaccines. Globally, more than 70% of cervical cancer cases are associated with infections with the high-risk HPV16 and HPV18 subtypes, and bivalent vaccination is sufficient to effectively prevent these two infections. Due to China's large population, the government must be careful in order to use limited vaccine resources and local finances to the people who need to be protected the most, which requires accelerating the government-led HPV vaccination project to guide the vaccine market to develop in a more benign direction.

HPV publicly-funded vaccines are gradually rolled out

Throughout last year, four cities in Jiangsu, Wuxi, Lianyungang, Nanjing and Yangzhou, have successively carried out the pilot work of free HPV vaccination for school-age girls, with a total of 4,6 people vaccinated.

According to Jiangsu Province's "Work Plan for Free HPV Vaccination for School-age Girls", in 2023, the province will provide free vaccination of domestic bivalent HPV vaccine for at least 24,67 girls born after September 2009, 9 and in the first half of the year. In order to ensure the smooth implementation of the project, the province's finances at all levels will invest 1 million yuan.

Yicai noted that as early as December last year, Jiangsu Province issued the "12th Five-Year Plan" for the development of women and children, which proposed to "encourage areas with conditions to promote HPV vaccination with a focus on 9~15-year-old girls".

In January this year, Jiangsu Province released the "1 List of 2023 Facts on Ensuring and Improving People's Livelihood in 13 Categories", and "Free HPV Vaccination for School-age Girls" was included, which means that the vaccination project will be promoted in the province.

"The project is led by the Provincial Health Commission and launched in conjunction with the Provincial Department of Education and the Provincial Women's Federation in the province, aiming to enhance the public's awareness of cervical cancer prevention and treatment through HPV vaccination, and prevent and reduce the occurrence of cervical cancer." Jiangsu Provincial Health Commission said.

In addition to Jiangsu, according to this year's Hainan Provincial Government Work Report, "HPV vaccination for women of appropriate age" is also included in the 2023 practical matters identified by the provincial party committee and provincial government in 10.

The official website of the People's Government of Hainan Province released news in early February, further clarifying the vaccination plan: this year's project implementation scope is 2 cities and counties in the province (except Sansha City), and the vaccination target in 18 is girls aged 2023~1 and a half years old for the first dose, and girls who have contraindications to vaccination or girls who have been vaccinated with HPV vaccine are not included in the scope of vaccination. In 13, it is planned to vaccinate 14,2023 girls, according to the "5-58" two-dose immunization procedure, and complete the two doses of vaccination that year to ensure that "all should be received". At the same time, the project will also vaccinate female servicemen of appropriate age who need it with the domestic bivalent HPV vaccine.

Up to now, according to incomplete statistics, in less than three years, Hainan, Jiangxi, Tibet, Fujian, Jiangsu, Guangdong, Chongqing and other provinces, as well as Ordos, Linxia Hui Autonomous Prefecture, Qingdao, Jinan, Dezhou, Jiaozhou, Yantai, Shijiazhuang, Handan, Tangshan, Chengdu, Mianyang, Aba Tibetan and Qiang Autonomous Prefecture, Zhengzhou, Ningbo and other places are promoting publicly-funded HPV vaccination projects.

Looking back at the promotion process of HPV vaccine, in August 2020, China's first government-led free HPV vaccine vaccination project was launched in Junger Banner, Ordos City, Inner Mongolia.

Six months later, China launched the Healthy City Innovation Pilot in March 2021, encouraging participating cities to study and carry out government-led HPV vaccination according to their own circumstances. Up to now, among the first batch of 3 healthy cities, 15 cities, including Shenzhen, Xiamen, Chongqing, Ordos, Jinan, Chengdu and Wuxi, have officially launched HPV vaccine immunization programs.

In addition to Jiangsu, among the provinces where the above-mentioned cities have launched the HPV vaccine immunization program, Fujian and Guangdong provinces have also expanded the coverage of the project to the whole province, while Shijiazhuang, Tangshan, Zhengzhou and Hainan, Jiangxi, Tibet and other places not included in the aforementioned pilot list have also announced free HPV vaccination worldwide.

For example, Guangdong proposed that in 2022~2024, the financial plan will add about 6 million yuan for free HPV vaccination, and from 2022, free vaccination will be implemented for girls under the age of 9 who have Guangdong Province student status and have newly entered the first grade of junior high school from September and have not been vaccinated with HPV vaccine.

Why bivalent seedlings are critical

At present, HPV vaccine has not been included in medical insurance in China, and with the expansion of vaccination in many places, the three-dose nine-valent vaccine vaccinated at self-pay has become a tight existence in the market. However, in the view of industry insiders, if China wants to achieve the "2030-90-70" goal proposed by the WHO by 90, it is urgent to promote the government-led bivalent vaccination program.

The so-called "90-70-90", that is, 90% of girls complete HPV vaccination before the age of 15; 70% of women are screened by 35 and 45 years of age with highly effective testing methods; Ninety per cent of women diagnosed with cervical disease receive treatment. In 90, China had 2020,10 new cases of cervical cancer and 9,5 deaths, accounting for one-fifth of the global total.

Currently, HPV vaccines are divided into bivalent, quadrivalent and nine-valent. All HPV vaccines contain VLPs (virus-like particles) against high-risk HPV16 and 18; Among them, the nine-valent vaccine contains VLPs against high-risk HPV31, 33, 45, 52 and 58.

According to the WHO's Human Papillomavirus Vaccine: WHO Position Paper, updated last year, it is estimated that HPV16 and HPV18 together cause 71% of cervical cancer cases worldwide. Of the remaining 29% of cervical cancer cases, HPV45 accounted for 6%, HPV31 4%, HPV33 4%, HPV52 3%, and HPV58 2%.

The WHO cited research in the document to say that the bivalent (Cervarix) vaccine is also highly effective against infections and cervical lesions associated with HPV16 and HPV18. "A study looking at population-based cancer registry data in women under 30 years of age found that after the bivalent (Cervarix) HPV vaccine was included in the national immunization program, cervical cancer could be nearly eliminated in women who were vaccinated at the age of 12~13."

For why the public-funded vaccination plan chose domestic bivalent HPV vaccine, Jiangsu CDC also gave an explanation: in China, about 70% of cervical cancer cases are related to high-risk HPV16 and HPV18 two subtypes of infection. The HPV vaccine project for girls of appropriate age uses domestic bivalent HPV vaccine, and 9~14-year-old subjects need to receive 2 doses, which can effectively prevent the infection of the above two subtypes and is the most cost-effective vaccine.

Du Heng, senior project officer of the Beijing Representative Office of the Bill & Melinda Gates Foundation, believes that enterprises will make capacity layout and arrangements according to market demand. If the government does not guide, enterprises will only focus on the commercial market, leaving production capacity to high-priced vaccines and people with higher ability to pay, and will not give priority to key 9~15-year-olds.

However, the reporter noted that the main target group of HPV vaccination recommended by WHO includes girls aged 9~14 years who have not had sex. However, in Jiangsu, Hainan and other places, the age range of the first dose of the first dose of women who are included in the HPV vaccine at public expense is about 1~13 years old.

For this phenomenon, the team of Zhao Fanghui, director of the Epidemiology Research Office of the National Cancer Center and Cancer Hospital of the Chinese Academy of Medical Sciences, found that considering the limited vaccine and financial resources, the first two doses of vaccination to 9-year-old girls will benefit more than other age groups first. "The key point of optimizing the prevention and control strategy of cervical cancer in China is to change from 'treatment-oriented' to 'prevention-oriented', increase the initial investment, and introduce vaccines in the small age group of 14~14 years old as soon as possible."

As more provinces include bivalent HPV vaccines in the scope of public vaccination, can China's production capacity be covered?

Chai Yan, director of IQVIA Management Consulting, said that there are two domestic companies that can produce HPV vaccines, each with a total production capacity of up to 3000 million / year, but the current production capacity of both companies is not full. According to preliminary forecasts, in 2023, the demand for bivalent seedlings in China will be 1 million. In theory, if the two manufacturers operate at full power, they can meet the demand of most consumers for bivalent vaccines in recent years.

"Based on this, it is expected that after 2025, China will usher in a new stage of HPV vaccine development." At that time, a number of domestic vaccines will be launched one after another, greatly improving the overall supply of HPV vaccines in China and improving the accessibility of vaccines. Chai Yan said.

Du Heng also believes that promoting the inclusion of HPV vaccine in immunization programs can fundamentally solve the problem of vaccine quality, supply and price. The government's dominance of the vaccine public market allows enterprises to have a stable source of bulk orders, and then have the confidence to expand production capacity, and in order to ensure large-scale production supply, they are more willing to invest more R&D and human resources in quality control to improve product efficiency. Governments and the public can also benefit from access to high-quality and affordable cervical cancer vaccines.