“Have you had the HPV vaccine?” Many people will talk about this topic.
As the first cancer vaccine in human history, the birth of HPV (human papillomavirus) vaccine makes cervical cancer the first malignant tumor that can be “eliminated” .
It has been nearly 6 years since my country approved the first HPV vaccine in July 2016. At present, there are three HPV vaccines available on the domestic market: bivalent, quadrivalent, and nine-valent.
“It takes two or three years to make an appointment, and it is not impossible for more than three years.” “We have more than 10,000 people in the queue now.” It has not been vaccinated yet” “I’m not sure when the seedlings will come, even if they come, there will be hundreds of seedlings, and the second and third injections must be given first”…
< p>Why is the HPV vaccine still in short supply in my country even though it has been on the market for several years and there are a variety of products to choose from? With the relay research and development and approval of domestic vaccines, when will the majority of school-aged people realize “HPV vaccine freedom”?
Text| “(ID: ENNWEEKLY), the original text was first published on May 2, 2022, with the original title “The appointment will be scheduled for two or three years, why is this anti-cancer product “hard to get a dose”? “”Two prices, four prices, nine prices? One stitch, two stitches, three stitches? How to choose? “.
1
First Cancer Vaccine
When it comes to the HPV vaccine, we must first talk about cervical cancer.
Cervical cancer is one of the common gynecological malignancies. According to the “Global Cancer Statistical Report” released by the International Agency for Research on Cancer (IARC), a subsidiary of the World Health Organization, in 2020, the number of new cervical cancer cases in my country will be nearly 110,000, and the number of deaths will be about 59,000.
In other words, every 10 minutes on average, a woman in our country is killed by cervical cancer.
The data is brutal, but people are not helpless. Cervical cancer is currently the only tumor disease with a clear etiology and a slow onset process. More than 95% of cervical cancers are caused by HPV (human papillomavirus), and are mainly persistently infected by several high-risk HPV types (HPV16, HPV18, etc.). caused.
Moreover, from HPV infection to cervical cancer is a gradual development process, which generally takes several years or even ten years. This provides sufficient time for early detection, early prevention and early intervention of cervical cancer, which is beneficial to reduce morbidity and mortality.
At present, in addition to the promotion and popularization of cervical cancer early screening to help early detection and early intervention, human beings also have a powerful defense weapon – HPV vaccine. For cervical cancer and other lesions caused by HPV virus infection, HPV vaccination is the best known prevention method.
In countries and regions with high HPV vaccination coverage, the incidence of HPV infection and cervical cancer decreased significantly.
For example, the United Kingdom has included the HPV vaccine into the National Immunization Program (NIP) since 2008, providing routine vaccination of bivalent HPV vaccine to girls aged 12-13. , and provide replanting for women aged 14-18. In November 2021, the authoritative medical journal The Lancet published a study based on diagnostic data on cervical cancer and cervical precancerous lesions in women aged 20-64 living in England during the 13 years from 2006-2019, and found that , Cervical cancer rates plummeted among women who received the HPV vaccine. Researchers say the HPV vaccination program has reduced the incidence of cervical cancer in women born after September 1, 1995, to 3 in 1 million people, almost eliminating the possibility of cervical cancer in these people.
The World Health Organization also launched the “Global Strategy to Accelerate Cervical Cancer Elimination” in 2020, announcing that 194 countries, including China, will jointly seek to achieve 90% by 2030. % of girls complete HPV vaccination by age 15. According to the World Health Organization, 117 countries have included HPV vaccines in their national immunization programs.
my country approved the first HPV vaccine in July 2016. Currently, there are three HPV vaccines available on the domestic market: bivalent, quadrivalent and nine-valent. for selection. The “Outline for the Development of Chinese Women (2021-2030)” issued in September 2021 proposes to promote the pilot work of HPV vaccination for women of appropriate age.
▲The strategy of HPV vaccination of school-age women is gradually promoted in many places across the country. Source: Guosen Securities Research Report
At present, many regions in China have started free HPV vaccination for school-age women or Provide vaccination subsidies.
For example, as the first city in the country to start free vaccination of HPV vaccines for school-aged people, Xiamen will start free vaccination of domestically produced HPV vaccines for girls aged 13 to 14 and a half years old in 2020. price vaccine.
Chengdu has adopted a more flexible subsidy policy, that is, for “female students aged 13-14 years old”, financial funds will be given to 600 yuan/person for vaccination Subsidies, parents of students can choose between domestic/imported bivalent and imported quadrivalent HPV vaccines.
Guangdong Province proposes that about 600 million yuan will be added for free HPV vaccination in 2022-2024, and the 14 students who have a student status in Guangdong Province, who have entered the first grade of junior high school from September and have not been vaccinated against HPV vaccine Girls under the age of one year are free to receive the domestic bivalent HPV vaccine.
▲A promotional poster for free HPV vaccination for school-age girls in Guangdong.
Wang Linhong, chief expert on chronic diseases of the Chinese Center for Disease Control and Prevention, believes that with the application of HPV vaccine in China, from the perspective of national prevention and control strategies, cervical cancer prevention will be Secondary prevention, which focuses on early screening, has been transformed into HPV vaccine application of both etiological prevention and early screening, and a qualitative leap has taken place in prevention and control methods.
2
It’s not easy to make an appointment< /span>
The benefits of HPV vaccination come from Needless to say, but the problem faced by many people at present is that it is not easy to make an appointment for a dose of vaccine.
According to the reporter’s understanding, the imbalance between supply and demand of domestic HPV vaccine is prominent, and the situation of “difficulty in making an appointment” is common. The price of HPV vaccine is even more difficult to get one dose. According to reporters’ interviews with vaccination sites in various places, at present, imported HPV vaccines are generally out of stock and in short supply. Among them, the quadrivalent HPV vaccine is the most “scarce”, and the vaccine cycle is uncertain.
“It may be once a month, it may be once every 2 months, or even once every six months. I can’t promise.” A community health service in Nankai District, Tianjin Center said.
▲Imported quadrivalent “HPV vaccines” in multiple cities across the country Out of Stock” or “Subscription Paused”.
At present, there are thousands or even tens of thousands of people queuing up at many vaccination sites. It said that “it will take at least two or three years”, and some said that “the first appointment is not accepted for the time being” and “the appointment is also a blank check”.
For example, a person from a community health service center in Jiangbei District, Chongqing told reporters, “Since the end of last year to the present, our center has not visited the four-price seedlings.”
Nine-valent HPV vaccine is also in short supply. Some community health service centers can come to the seedlings every two or three months, but every time after the seedlings arrive, the number source released by the reservation platform almost disappears in seconds.
It is understood that the quadrivalent HPV vaccine is suitable for women aged 20-45, and the nine-valent HPV vaccine is suitable for 16-26 aged female. From the perspective of age span, the quadrivalent includes more people, which may be an important reason for its popularity.
In addition, every time the inoculation site arrives at the seedling, it will generally give priority to those who have received the first or second injection in the previous sequence. That is to say, after a successful appointment, three injections are guaranteed by default, and the next two injections are directly arranged by the vaccination clinic. In this case, it is even more difficult to make an appointment for the first vaccination.
The imported bivalent HPV vaccine is also out of stock. However, people from multiple vaccination sites told reporters that there were not many people who made appointments to import bivalent seedlings.
▲On the vaccine reservation platform “About Vaccine”, the imported two-valent and nine-valent HPV vaccines are also “one dose” Hard to find”.
Faced with the phenomenon of “more monks and less porridge” in imported HPV vaccines, in order to ensure fairness , Shenzhen, Hangzhou and other cities use the “lottery” method to make an appointment.
From the public data of a set of lottery numbers disclosed by the Shenzhen Municipal Health Commission on March 8, it can be seen how difficult it is to obtain the nine-valent HPV vaccine: a total of 527,121 people participated and 21,170 people were acceptedThis kind of opportunity, the winning rate is only 4%.
It is not easy to get an appointment for an imported vaccine in a public medical institution, and some people choose to go to a private hospital to try their luck.
The reporter saw on the e-commerce platform that many private hospitals provide quadrivalent and nine-valent HPV vaccination services, and some areas have stock.
However, not always available after purchase. “The number of people vaccinated by the hospital is limited every day. If the vaccine is in stock, it is estimated that the first dose of vaccination can be arranged in 1-2 months. The specific time depends on the hospital’s schedule.” A private medical institution Agency staff told reporters.
▲Private hospitals can also make appointments for four-price and nine-price HPV vaccines, but the queue time is shorter than that of public institutions. The price is higher.
In addition, the price of vaccination in private hospitals is much higher than that in public medical institutions. It is understood that the price of HPV vaccination in public medical institutions is the delivery price of the vaccine plus an inoculation service fee of about 25 yuan. For example, the cost of a single injection of the quadrivalent vaccine is about 823 yuan, and the nine-price vaccine is about 1323 yuan per injection. Private hospitals generally cost more than 1,200 yuan per injection for a four-price injection, while a nine-price injection costs more than 2,000 yuan per injection, and the total cost of three injections needs to be paid at one time.
“Scalpers” are also eyeing this business. According to Xinhua Viewpoint, there are a large number of nine-valent HPV vaccine appointment advertisements on the online platform, and the cost of appointment and snatch ranges from a few hundred yuan to several thousand yuan. The business of vaccine “scalpers” covers major cities across the country, and some “scalpers” claim to “call at any time within a week after making an appointment.”
“We will help you submit an appointment with the internal vaccine quota, and you can make an appointment in the near future.” A vaccine “scalper” told reporters.
▲There are “scalpers” claiming that the nine-price HPV vaccine is ready to be administered on social platforms.
It is worth noting that due to the difficulty in obtaining one dose of imported quadrivalent and nine-valent HPV vaccines, many people have Hope to get vaccinated before the age limit, which also gives crooks the “opportunity” to fish in troubled waters.
In recent years, quadrivalent and nine-valent HPV vaccine scams have occurred from time to time. For example, according to a report from the Jiangbei District Health and Health Commission of Chongqing City, some people privately charged other people’s fees for helping to make an appointment for cervical cancer vaccine, and pretended to be quadrivalent and nine-valent HPV vaccine with normal saline and bivalent HPV vaccine; Fraudulent transactions for HPV vaccines to defraud money.
▲According to the fourth price of HPV vaccine in Jiangbei District, Chongqing , Nine-valent HPV vaccine.
In this regard, the police in many places reminded that the appointment of the nine-valent cervical cancer vaccine must be made through official channels. You can’t buy the so-called “special vaccine” just because you are greedy for cheap.
3
Supply gap in the hundreds of millions
< p> “The shortage of quadrivalent and nine-valent HPV vaccines is not a matter of one or two years. It has been in short supply since its launch.” A person from the CDC in Jizhou District, Tianjin told reporters.
The quadrivalent and nine-valent HPV vaccines were approved and marketed in China in May 2017 and April 2018, respectively, and they have been available for several years. Medicines are hard to find”?
A person from the Anqing Center for Disease Control and Prevention pointed out the contradiction between the supply and demand of imported vaccines: “There are very few vaccines, but those who want to fight are not There are too many.”
From the perspective of overall supply, there are currently 5 HPV vaccines in the domestic market, namely LanxoSmithKline, Wantai Bio and Watson Bio’s bivalent HPV vaccine, as well as Merck’s quadrivalent HPV vaccine and nine-valent HPV vaccine.
Among them, GlaxoSmithKline was first approved in China in July 2016. Subsequently, in May 2017 and April 2018, two of Merck’s vaccines were approved.
Xinke Ning, a subsidiary of Wantai Bio, was approved in December 2019 as the first domestic HPV vaccine. A bivalent HPV vaccine developed by Shanghai Zerun, a subsidiary of Watson Bio, was approved for marketing in March this year, but it has not yet been sold.
Therefore, only Merck is the only supplier of quadrivalent and nine-valent HPV vaccines in China. It is also the only manufacturer of quadrivalent and nine-valent HPV vaccines in the world.
According to the batch issuance of biological products by the China National Institute for Food and Drug Control, since its launch, the number of HPV vaccines in my country has increased. The number of batches issued has increased significantly. But relative to the demand of the crowd, it is far from enough.
▲The number of batches issued since the domestic HPV vaccine was launched, unit: ten thousand. (From the research report of West China Securities. Then update the specific data of vaccine batch issuance, so the batch issuance volume in 2021 is the estimated data.)
The data from the Huaxia Securities Research Report shows that by the end of 2021, four The total number of HPV vaccines issued in batches is about 22.91 million, and the nine-valent HPV vaccine is 18.61 million.
However, according to three doses per person, the two imported vaccines are only enough for 13.84 million Even if the two bivalent vaccines are included, from the launch of the first HPV vaccine to the end of 2021, the total batch issued is 61.9 million, which can only satisfy more than 20 million people to complete the whole course of vaccination.
So, how big is the gap?
The research report of Huaxi Securities estimates that the current number of females aged 9-45 in China is about 381 million. According to the current 20 million people who have completed the vaccination, the penetration rate of HPV vaccination in domestic women of school age is only about 5%. If the penetration rate of women of school age is 30%, 45% and 60%, the domestic HPV vaccine needs 2.8% respectively. If you want to achieve 100% penetration, the gap will exceed 1 billion.
It is worth mentioning that since the approval, Merck has almost The supply in China will increase every year. For example, in 2018, the batch issuance of the nine-valent HPV vaccine was only 1.216 million, but by 2020, the batch of the nine-valent vaccine has reached 5.066 million. In 2021 In the first half of the year, the batch issuance of the 9-valent vaccine further increased to 11.097 million.
However, due to the need for Merck to supply the global market , even if the production capacity is increased, the share of the domestic market that can be increased is still limited.And compared with the hundreds of millions of females of school age in China, the supply of imported vaccines can be said to be a drop in the bucket.” I’m afraid it will continue for some time.
4
p>
Compared with imported vaccines that usually have to wait for two or three years, domestic bivalent HPV vaccines are much more “friendly” to book. Most of the vaccination sites can arrange the first vaccination within 1 month. However, many people who are willing to be vaccinated still prefer imported quadrivalent or nine-valent vaccines with higher prices and higher prices.
What does the higher price mean?
As mentioned above, more than 95% of cervical cancers are caused by HPV, and there are more than 200 known HPV types. All types are immunized, and only a few of them can be selected.
Different types of viruses have different health risks. According to whether they are carcinogenic or not, HPV is divided into high-risk and low-risk types. According to the recommendations of the World Health Organization International Agency for Research on Cancer, the State Food and Drug Administration defines HPV16/18/31/33/35/39/45/51/52/56/58/59/68 as high-risk types.
Among them, HPV16/18 had the highest risk of carcinogenesis. Studies have shown that among cervical cancer patients, the infection rate of HPV16 is 55.2%, and the infection rate of HPV18 is 14.2%. In other words, about 70% of cervical cancers are caused by these two high-risk types.
The currently available bivalent, quadrivalent and nine-valent HPV vaccines have good protective effects on these two high-risk types. In terms of the preventive effect on cervical cancer, there is almost no difference between bivalent and quadrivalent vaccines, and the protective efficacy is about 70%. However, the quadrivalent HPV vaccine has two more low-risk types, HPV6 and HPV11, which are more effective than bivalent HPV. The vaccine has added indications for the prevention of condyloma acuminatum. On the basis of the quadrivalent HPV vaccine, 5 new high-risk types have been added. Compared with the bivalent and quadrivalent vaccines, the preventive and protective effect on cervical cancer is increased by about 20%.
▲This publication makes a list. Data sources: vaccine instructions, announcements of listed companies, official website of the State Food and Drug Administration, etc.
Different vaccine prices do mean different protective effects. However, the effect of vaccine protection is also affected by the age of vaccination.
Simply put, the earlier the age-appropriate population is vaccinated, the better the effect of preventing cancer.
Cervical cancer and precancerous lesions among the youngest vaccinated women, according to the above-mentioned Lancet study on women vaccinated against HPV in the UK The rate dropped the most. Specifically, the incidence of cervical cancer was reduced by 87% in the vaccinated group aged 12-13 years and by 62% in the group vaccinated at 14-16 years of age compared with the control cohort not vaccinated against HPV In terms of cervical precancerous lesions (CIN3), the incidence of vaccination at the age of 12-13 was reduced by 97%, the incidence of vaccination at the age of 14-16 was reduced by 75%, and the incidence of vaccination at the age of 16-18 was reduced by 75%. Vaccination incidence was reduced by 39%.
The World Health Organization recommends that the main target population for HPV vaccine vaccination is adolescent women who have not been exposed to vaccine-related HPV genotypes. Both the U.S. Advisory Committee on Vaccination and Immunization Practices and the U.S. Centers for Disease Control and Prevention recommend HPV vaccination starting at age 11 or 12, or starting at age 9.
Chinese Experts on Clinical Application of Human Papillomavirus Vaccine issued by Chinese Medical Association Gynecological Oncology Branch and Chinese Eugenics Association Colposcopy and Cervical Pathology Branch Consensus” mentioned that the benefits of HPV vaccination for 13-15-year-old women before their first sexual activity can be maximized, and HPV vaccine is recommended for 9-26-year-old women, especially women before the age of 17; at the same time, 27-45 Conditional females are vaccinated against HPV. It is precisely because of this that many experts call for people of appropriate age to be vaccinated as soon as possible, and not to blindly wait for “high” price vaccines and miss the best time for vaccination.
“Compared with the expensive and insufficient supply of the quadrivalent and nine-valent HPV vaccines, the bivalent vaccine is more cost-effective in preventing cervical cancer.” Guiyang CDC said.
5
How close is HPV vaccine freedom
< p>The reporter learned that the domestic bivalent HPV vaccine can be vaccinated at any time at the vaccination sites in many cities across the country, and some vaccination sites need to be booked in advance, and most of them can start the first shot within a month.
▲A nurse injects a girl from Wuhan with domestic HPV vaccine. Photo by Xinhua News Agency reporter Xiong Qi
From the perspective of price, the domestic bivalent HPV vaccine is more friendly to the people. Wantai Bio’s Xinkening single injection price is 329 yuan, plus the inoculation service fee, the total cost of 3 injections is over 1,000 yuan. Not only the price is favorable, but the advantages of domestic vaccines are also reflected in the vaccination procedures. For women aged 9-14, only two injections are required, which costs about 600 yuan, which greatly reduces the vaccination time and economic cost.
Following Wantai Bio, Watson Bio, a domestic company, has also approved a bivalent HPV vaccine this year, but it has not yet launched. It is understood that the company has started the production of the vaccine in early April, and vaccination can be carried out after the batch is issued.
In terms of production capacity, the supply potential of the two domestic HPV vaccines is also considerable. According to the company’s announcement, the annual production capacity of Wantai Bio’s bivalent HPV vaccine is 30 million, while the designed annual production capacity of the bivalent HPV vaccine production workshop of Yuxi Zerun, a subsidiary of Watson Bio, is also 30 million.
However, even so, the two production lines are running at full capacity and can only satisfy more than 20 million people each year to complete the whole course of vaccination.
Moreover, considering the differences in vaccines at different prices, as well as the diversified and multi-level needs of domestic consumers, it is still There needs to be more “higher priced” vaccines.
As mentioned above, the current domestic quadrivalent and nine-valent HPV vaccines are only supplied by a single manufacturer of Merck & Co. Even if its production capacity is increased, it cannot meet the vaccination needs of the large domestic population of appropriate age .
In the end, it is hoped that the “HPV vaccine freedom” for the majority of school-aged people will ultimately depend on domestic vaccine manufacturers.
Faced with the huge supply gap, many companies have joined the HPV vaccine research and development queue. According to the reporter’s incomplete statistics, as of now, there are at least 17 HPV vaccines under development in China, of which 8 have entered the phase III clinical trial stage, including 4 9-valent vaccines, 2 quadrivalent vaccines, and 1 11-valent vaccine and a trivalent vaccine.
▲Basic situation of HPV vaccines under research in China. This publication is tabulated
However, from clinical trials to actual approval for marketing, it still needs to go through many tests.
In terms of development time alone, Watson’s bivalent HPV vaccine has been developed for 17 years. The product was approved for clinical trials in June 2011. The marketing application was accepted in January, and the entire clinical cycle lasted about 9 years; the bivalent HPV vaccine under Wantai Bio started the Phase I clinical trial in 2010, and submitted the application for marketing registration in 2018. The whole process lasted more than 8 years.
It can be seen that it will take some time before the vaccines in the research stage are finally approved to enter the market.
Take Wantai Bio’s nine-valent HPV vaccine as an example, which completed the first subject enrollment in September 2020. According to the company’s estimate The clinical program is designed to complete the entire phase III clinical trial cycle in about 66-78 months, which is about 5.5-6.5 years.
This means that if all goes well, we are expected to have a domestic nine-valent HPV vaccine by the end of 2024 or early 2025.
The Guosen Securities Research Report believes that several domestic HPV vaccines in phase III clinical trials are expected to be launched around 2025. At that time, a product pattern of “2 imported + 6 domestic” products may be formed.
In addition, it is worth mentioning that although many products are in the process of research and development, some companies have begun to expand production in order to shorten the production time after the vaccine is approved.
“If the production capacity under construction is successfully put into production as planned, the production capacity of HPV vaccine will be greatly increased from 2025.” Guosen Securities Research Report is the judgment.
At that time, for many people, it may be much easier to get about one shot of the quadrivalent or nine-valent HPV vaccine.
6
One shot, will it work?
< /p>
Recently, many people have also paid attention to the single-dose vaccination recommendation of the HPV vaccine proposed by the World Health Organization on its official website.
Specifically, the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) meeting reviewed the evidence for single-dose HPV vaccination and concluded that a single-dose HPV vaccination regimen is effective in preventing Cervical cancer caused by persistent HPV infection and is comparable to two- or three-dose regimens.
To this,different
strong>The response of the crowd varies greatly. Those who have just finished the first injection may be more happy and feel that the money for the next two injections has been saved;Cheng’s may feel that he is at a loss, and the last two shots are in vain; for those who have not yet made an appointment, I hope that it will be easier to make an appointment later.
What are the facts? What is the basis for this discussion by the World Health Organization? Will my country’s HPV vaccination schedule change next?
First of all, many people interpret this news as “one needle is enough”, which in fact greatly simplifies the recommendations of the World Health Organization.
On the official website of the World Health Organization, the immunization program recommended for HPV vaccine is listed in detail, and it is divided into the following situations: Women aged 9-14 are the highest priority group and receive one or two doses. Dosage; young women 15-20 years old, can use a single-dose or two-dose regimen; women over 21 years old, should use a two-dose regimen with an interval of 6 months; HIV-infected people and other immunocompromised people should be Three doses or at least two doses.
In other words, except for women aged 9-20 who do not have low immunity problems, they can choose a one-dose vaccination plan, and the others still need to be vaccinated with two or three doses.
An expert from the Guangdong Provincial Center for Disease Control and Prevention told reporters that the more consideration behind the World Health Organization’s proposal is that due to the impact of the new crown pneumonia epidemic and insufficient vaccine supply, the rate of HPV vaccination in many countries has slowed down , and single-dose vaccination can effectively increase HPV vaccination rates, especially in low-income countries.
The Guoxin Pharmaceutical Research Report believes that most of the research results reviewed by this SAGE use persistent infection/immunogenicity in the young age group as a surrogate endpoint. The peak dose of vaccination and the long-term antibody titer were both lower than the 2/3 doses of the immunization program. More data and continuous tracking in a longer time dimension are still needed for the long-term protection efficacy of cervical cancer.
In my country, a series of clinical studies, data support and marketing registration procedures are required to determine the vaccination procedure for vaccines. At present, for several HPV vaccines that have been approved in China, the immunization procedures of imported bivalent, quadrivalent and 9-valent vaccines are all three doses, and the two domestic bivalent HPV vaccines are also immunized with three doses, but for women aged 9 to 14 years old The population can take two doses.
In other words, at present, this discussion proposed by the World Health Organization will not change my country’s HPV vaccination program for the time being, and everyone should still follow the vaccine instructions approved by the regulatory authorities.
Uncle Ku Welfare
< p>Uncle Ku’s book donation activity is always on! Renmin University of China Press provided Uncle Ku with 25 copies of The Seven Business Giants Affecting American History For avid readers. This book tells the stories of seven of the great entrepreneurs in American history. The author puts the entrepreneurial process of seven entrepreneurs in the context of the times, reflecting the process of the United States surpassing the United Kingdom through industrial innovation and achieving economic rise. Looking back on this history, it is a must-read business classic for today’s China. Please leave a comment under the article, and the top 3 likes (more than 50) will get a free book.
< /img>