"One dose of HPV vaccine is effective in preventing cervical cancer, which is comparable to two or three injections." This is the latest recommendation from the World Health Organization's (WHO) Strategic Advisory Group on Immunization (SAGE).
As a female malignancy with an incidence second only to breast cancer, cervical cancer is the only cancer with a clear cause in humans - a lesion caused by human papillomavirus (HPV); and the only cancer that humans can currently prevent - HPV vaccination.
However, due to the low production capacity and insufficient supply, many people have not yet applied this vaccine. #Produce HPV vaccine anxiety # and other HPV vaccines are difficult to find a topic that has repeatedly become a hot search.
Can SAGE's latest assessment change that?
What does it mean that the HPV vaccine works with a single shot
At present, a total of 5 HPV vaccines have been approved for marketing worldwide, requiring 2 or 3 injections. The recommendation that one injection can be given means that the HPV vaccine will be more than twice as fast as it is now under the premise of constant production capacity.
However, SAGE's recommendations are not final. The WHO said it would hold a meeting to discuss the stakes before the position paper on the HPV vaccine was formally revised.
Even if the WHO later revises the vaccination procedure proposal and adopts it in China, it will take a long time. According to the policy of the State Food and Drug Administration, if the vaccine is to be changed in the number of doses, a series of clinical data support needs to be fulfilled to ensure that the vaccine is effective for the local population in China. This process is often calculated in years.
And although studies have shown that the protection effect of a single dose of HPV vaccine is indeed good, so far, a single dose of HPV vaccine still lacks clinical data support. SAGE's "quick" recommendation also takes into account the current shortage of HPV vaccines. WHO Assistant Director-General Nothemba (Nono) Simelela said: "This single-dose recommendation is likely to enable us to achieve our goal of eliminating cervical cancer faster. ”
The WHO's global strategy to accelerate the elimination of cervical cancer proposes that by 2030, 90% of girls will be vaccinated against HPV by the age of 15. However, due to vaccine shortages, this figure reached 13% in 2020.
China faces similar challenges.
According to the estimation of Song Yifan and others of the Immunization Program Center of the Chinese Center for Disease Control and Prevention, from July 2016, when GlaxoSmithKline became the first HPV vaccine approved for marketing in China, by the end of 2020, the HPV vaccination rate of women of appropriate age in China was 2.24%. Although the vaccination rate in Beijing, Shanghai and other cities ranks among the highest in China, it has only reached 7 or 8 percent.
The new crown vaccine from research and development to marketing to a large number of vaccinations, only a few years, compared with the HPV vaccine vaccination rate can be described as a slow growth, why is this so? The answer is that capacity can't keep up.
Although HPV vaccines have been developed for more than 30 years, to date, only 4 vaccine manufacturers in the world are producing HPV vaccines. And before the domestic divalent vaccines of Wantai Bio and Watson Bio were listed, for a long time, the world relied on two multinational pharmaceutical companies, GlaxoSmithKline and Merck, to provide vaccines.
As the world's only supplier of quadrivalent and nine-valent HPV vaccines, Merck pledged in early 2022 to significantly increase its supply of HPV vaccines to China. But compared with the hundreds of millions of women of school age in China, the increased supply of the Merck family may be "a drop in the bucket".
In the end, it may be The Chinese vaccine companies that can finally solve this supply and demand problem.
Domestic HPV vaccine, production capacity soared
On the last day of 2019, the domestic bivalent HPV vaccine Xinkening developed by Wantai Biotech was approved for listing, priced at 329 yuan / needle, and women aged 9 to 45 can be vaccinated. At that time, the imported Cirishi, which was also a bivalent HPV vaccine, cost 580 yuan for one injection, and under 20 years old could not be vaccinated.
Cheaper prices and a wider range of vaccination age groups allowed Xinkoning to surpass Xi Ruishi in the first year of listing, quickly seizing the domestic market for divalent HPV vaccines. By 2021, Wantai Bio will issue 10.66 million bivalent HPV vaccines in one year.
With the recent listing of the second domestic bivalent HPV vaccine Wozehui, the shortage of HPV vaccines is expected to be further alleviated. Watson Biologics, which is responsible for the production of Wolzerhui, said that "a modern production base with a production capacity of 30 million doses of HPV divalent vaccine has been built."
However, compared with the bivalent HPV vaccine, which is becoming more and more easy to get, many people hope to get a quadrivalent or even a nine-valent HPV vaccine.
The so-called "valence" refers to the number of HPV virus models prevented by the vaccine. At present, more than 200 HPV models have been found in humans, not all of which are carcinogenic, and the vast majority of cervical cancer cases are due to infection with one of 14 high-risk HPV types. Bivalent HPV vaccines cover the two most common of these, while nine-valent vaccines cover 7 and 2 of these low-risk hpvies.
Because the higher the price, the more HPV virus species can be prevented, which makes the nine-valent HPV vaccine the most popular at present.
How hard is it to grab the nine price? Let's take a look at Shenzhen, which uses the lottery method to determine the vaccination opportunity: the results of the third phase of the nine-valent HPV vaccine lottery in 2022 show that a total of 527,000 people applied for this period, while the indicator was only 21,000, and the winning rate was only 4%.
This situation is also expected to be solved by domestic vaccines in the future.
At present, at least 14 HPV vaccines in Chinese pharmaceutical companies have entered the clinical research stage or been approved in clinical trials, nearly half of which are 9-valent HPV vaccines. Among them, several of the fastest-advancing nine-valent vaccines have entered the clinical phase III, which means that domestic nine-valent vaccines are getting closer and closer to the end of the market.
In addition to the nine-valent, higher-priced HPV vaccine has also entered clinical trials. According to the data released by Shenzhou Cells, the fourteen-valent HPV vaccine they developed covered all 12 high-risk HPV subtypes of cancer released by WHO, and the cervical cancer prevention rate increased from 90% of the nine-valent to 96%.
So many companies scrambling to develop HPV vaccines are also related to the profit potential of this market. With a bivalent HPV vaccine, Wantai Bio's vaccine business revenue in 2021 increased by 360.75% year-on-year.
The more intense the domestic vaccine "roll", the higher the chance that ordinary people will get the HPV vaccine in the future.
Universal hpvide vaccine, price is the key
In addition to increasing the production of HPV vaccines, the entry of domestic vaccines will also have a significant impact, that is, to reduce the price of HPV vaccines.
The price of a single bottle of Xinkonin is 43.3% lower than that of imported divalent HPV vaccines, and Wo zehui, which was listed in March 2022, further reduces the purchase cost of bivalent, with each priced at 319 yuan.
The reason why SAGE recommends a single dose of HPV vaccine is not only to consider the problem of vaccine production capacity is too low, but also to solve the high cost of vaccination.
A survey published in China Public Health last December showed that in Guangzhou, three-quarters of the women surveyed were willing to get the HPV vaccine, but more than 70 percent could not accept spending more than 1,000 yuan on the HPV vaccine.
This means that in addition to the domestic bivalent HPV vaccine, the current imported quadrivalent and nine-valent vaccines are too expensive for most people.
If you don't want to wait for a long time, the cost will be higher. Due to the current domestic 9-valent HPV vaccine has an age limit of 26 years old, many girls are worried that the queue time is too long to reach the end of the overage, and they do not hesitate to add money to private hospitals to play the spot nine price, and the final cost is often twice the guidance price.
However, the strange availability of HPV vaccines will not last forever. Zhang Jun, deputy dean of the School of Public Health of Xiamen University, said that the domestic HPV vaccine is expected to have a shortage of about 3 years, after which it will be oversupplied, the price will fall sharply, and enter the era of national immunization planning.
Although the HPV vaccine has not yet been included in the national immunization program or medical insurance coverage, the National Health Commission encourages areas with conditions to pilot hpvide vaccine free vaccination first and gradually promote it.
At present, dozens of cities in China have begun to pilot free HPV vaccination projects, and the primary target group of vaccinations is mostly girls around 14 years old.
And this is also the best age for HPV vaccination. After analyzing the effect of HPV vaccination in the United Kingdom from 2006 to 2019, some scholars found that the incidence of cervical cancer in women vaccinated with HPV vaccine at the age of 12 to 13 years old would be 87% lower than that of unvaccinated people; the incidence rate was reduced by 62% at 14 to 16 years old; and the incidence was only 34% lower when vaccinated at 16 to 18 years old.
But missing the best age doesn't mean it's ineffective. And even if the age is more than 26 years old, it is still possible to hit the nine price in the future. Merck has initiated Phase III clinical trials of the nine-valent HPV vaccine in the 9-19-year-old and 27-45-year-old female age groups in China, and the nine-valent appropriate age group is expected to be relaxed to 9-45 years old.
Perhaps, the post-90s generation will be the only generation in China that has age anxiety because it cannot play the nine-valent HPV vaccine.
bibliography:
1.WHO-《One-dose Human Papillomavirus (HPV) vaccine offers solid protection against cervical cancer》，https://www.who.int/news/item/11-04-2022-one-dose-human-papillomavirus-(hpv)-vaccine-offers-solid-protection-against-cervical-cancer
2. State Drug Administration - HPV vaccine and cervical cancer prevention, https://www.nmpa.gov.cn/directory/web/nmpa/yaopin/ypjgdt/20190722080001877.html
3. Song Yifan et al. - Estimated VACCINATION Rate of HPV Vaccine for Women Aged 9-45 in China from 2018 to 2020
4. China News Network - "The Urgent Demand for HPV Vaccination in China Multinational Enterprises: Will Significantly Increase Supply", https://www.chinanews.com.cn/cj/2022/01-11/9649162.shtml
5. Beijing News - "After 17 years of research and development, the second domestic HPV vaccine was approved, will there be a shortage of seedlings in the future?" 》，https://www.bjnews.com.cn/
6. Shenzhen Health Commission - "1564 little sisters are in! In March, Shenzhen nine-valent HPV vaccine lottery results were released! 》，https://mp.weixin.qq.com/s/
7. The Paper- "The world's first 14-valent HPV vaccine entered the second phase of clinical practice in China, is it safe after "increasing the amount"? 》，https://m.thepaper.cn/
8. Wantai Biology - Wantai Biology 2021 Annual Report
9.Milena Falcaro等-《The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study》