At noon on April 19, staff from the private hospital United Family sent out a snap-up link in the vaccine reservation group. The quantity of about 50 vaccines was available at 13:30.

Category：hotcomm

2024-12-17

Behind the shortage of vaccine supply

Involving the business of manufacturers and the revision of vaccination standards

The extent to which the HPV vaccine can truly prevent cervical cancer is also doubtful

The 24-year-old Shanghai girl Wang Han did not expect that the rush to grab concert tickets would be in the reservation HPV nine-valent vaccine reappeared.

At noon on April 19, staff from the private hospital United Family sent out a snap-up link in the vaccine reservation group. The quantity of about 50 vaccines was available at 13:30. Wang Han opened the purchase page 5 minutes in advance and purchased an additional nine-price package for 5,000 yuan. When the time comes, the payment page immediately becomes a blank while loading. After a few seconds, the word "out of stock" pops up. Wang Han refused to give up and continued to refresh the page. After more than ten minutes, she found a "leak". The moment he paid the bill, Wang Han felt that he had "completed a major event in his life."

In April last year, Ordos, Inner Mongolia, became the first city in the mainland to vaccinate girls aged 13 to 18 against HPV for free. Today, more than 12 provinces and municipalities in China have invited bids and procurements to vaccinate the public with the bivalent HPV vaccine for free.

On May 30, the National Health Commission held a press conference. Wang Linhong, chairman of the Women's Health Branch of the Chinese Society of Preventive Medicine and chief expert on chronic diseases at the Chinese Center for Disease Control and Prevention, said, "The country will promote the free HPV vaccination policy to cover more people. At the same time, it will increase multi-sector collaboration to gradually solve the problem of HPV vaccine supply. "Insufficient vaccine supply and other issues, and efforts to meet the demand for vaccination."

Behind the insufficient supply of vaccines, there are many issues related to the business of manufacturers, revisions to vaccination standards, and changes in prevention concepts.

On March 12, 2022, some school-age girls received the first dose of the bivalent HPV vaccine for free at the Changchuang Central Health Center in Haikou, Hainan Province. Picture/China-Singapore

The rule of 3 doses of vaccination is being revised

In early April, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) announced the results of a meeting saying: "A single dose of HPV vaccine can provide reliable protection, and it is equivalent to 2 doses or 3 doses." "The vaccine regimen is equally effective." At the same time, SAGE recommended that countries can choose a 1-dose or 2-dose vaccination regimen for girls aged 9 to 14 years old and women aged 15 to 20 years old.

HPV vaccine is an important measure to prevent cervical cancer caused by persistent infection with high-risk human papillomavirus (HPV). The valence of the HPV vaccine refers to the types of HPV virus subtypes that the vaccine can prevent. There are three types of HPV vaccines currently on the market: bivalent, quadrivalent and nine-valent. Typically, the number of doses given for HPV vaccination is 3. The

bivalent vaccine can prevent nearly 70% of cervical cancers caused by HPV types 16 and 18. On this basis, the quadrivalent vaccine adds protection against HPV types 6 and 11. Based on the quadrivalent vaccine, the nine-valent vaccine adds protection against five virus subtypes that can cause 20% of cervical cancer. It is currently the vaccine with the widest protection against HPV viruses in the world.

The domestic HPV vaccine market has long been monopolized by the British GlaxoSmithKline and the American Merck & Co. In March this year, Watson's Pichia pastoris recombinant protein cervical cancer bivalent vaccine "Wozehui" was approved for marketing. Prior to this, on New Year's Day 2020, the E. coli recombinant protein cervical cancer bivalent vaccine "Xingconin" jointly developed by Wantai and Xiamen University was approved for marketing by the State Food and Drug Administration, and a single dose was issued The price is 329 yuan.

After the WHO announced a one-to-two-dose vaccination plan, Wantai’s stock price fell by 20% from April 14 to April 25, Merck’s Chinese agent Zhifei Biotech’s stock price fell by 31%. Watson was also implicated. From April 19th to 25th, the stock price continued to fall for five trading days.

Judging from clinical trials, it is well documented that a single dose of vaccination has the same protective effect. Zhang Jun, dean of the School of Public Health of Xiamen University and a member of the "Xinconing" R&D team, said in an interview with " China News Weekly ": "The current experimental results show to a large extent that the protective effect of a single dose of vaccination is In the short term, it is equivalent to two or three doses. "

Behind the shortage of vaccine supply

Involving the business of manufacturers and the revision of vaccination standards

The extent to which the HPV vaccine can truly prevent cervical cancer is also doubtful

The 24-year-old Shanghai girl Wang Han did not expect that the rush to grab concert tickets would be in the reservation HPV nine-valent vaccine reappeared.

Behind the insufficient supply of vaccines, there are many issues related to the business of manufacturers, revisions to vaccination standards, and changes in prevention concepts.

On March 12, 2022, some school-age girls received the first dose of the bivalent HPV vaccine for free at the Changchuang Central Health Center in Haikou, Hainan Province. Picture/China-Singapore

The rule of 3 doses of vaccination is being revised

In June 2018, a study funded by the National Institutes of Health and led by a professor at the University of Washington in Seattle tracked 2,275 women who received a single dose of HPV vaccine. The results of the study showed that after two and a half years, HPV antibody retention rate was 98%.Another follow-up study published in the "Journal of the National Cancer Institute" in February 2020 showed that after a single vaccination of 134 people with GlaxoSmithKline's bivalent vaccine Cervarix, the preventive effect of HPV infection on was similar to that of . Two or three doses are equivalent and last for at least 7 years. When receiving the HPV vaccine, the interval between the first and second shots is usually 1 to 2 months, and the interval between the second and third shots is 6 months.

However, the ideal time for the HPV vaccine to last is no less than 40 years. Zhang Jun made a hypothesis: "If the vaccine is vaccinated at the age of 10, it must ensure that it still has a protective effect from the first sexual intercourse to the period of frequent HPV infection around the age of 50." However, the current research cannot prove that a single dose The long-term effective protection period of vaccination is comparable to that of multi-dose vaccination. Aimée Kreimer, a senior researcher in the epidemiology of infection and immunity at the National Cancer Institute , also pointed out that the duration of the sustainable effect of a single dose of vaccination requires more research to support.

As far as mainland China is concerned, domestically produced vaccines can partially alleviate the tight supply situation. However, the "Guangdong Expert Consensus on the Application of HPV Vaccine to Eliminate Cervical Cancer" released in September 2021 mentioned that the current domestic HPV vaccine immunity coverage rate is low. The vaccination rate among adolescents is less than 3%, and the vaccination rate among the entire population is less than 6%. Because supply exceeds demand, situations like Wang Han's need to rely on rush and luck to get the vaccine often happen. Last year, 420,000 people participated in the second nine-price HPV vaccine lottery in Shenzhen, and only 7,093 people won the lottery, with a chance of less than 1.7%.

Behind the "26-year-old panic"

"If you don't hit the nine-price mark before the age of 26, you will never have the chance again." Liu Si, a Shanghai girl who will turn 26 in November, keeps seeing similar messages on social media. However, due to the epidemic, her community has been under lockdown for nearly two months since March 24. "If I don't get vaccinated, I will have regrets in my life." During those two months, she was often surrounded by the anxiety of vaccination as she approached the age of 26.

html On June 1, Shanghai officially resumed work and production. Liu Si immediately made an appointment call to Wusong Hospital, Zhongshan Hospital Affiliated to Fudan University. But the other party told her that if she wanted to hit the nine-price mark, she would have to wait in line for 1 to 2 years.

For domestic women, the fear of vaccination with the nine-valent vaccine mostly occurs when they are close to 26 years old. Merck is the global exclusive manufacturer of the nine-valent HPV vaccine. In 2018, Merck's nine-valent HPV vaccine was approved in mainland China, and the vaccination scope is for women aged 16 to 26 years old.

The approved applicable groups of HPV vaccine in mainland China are not exactly the same as those in other countries. In the United States, the Food and Drug Administration expanded the scope of application of the nine-price product to men and women aged 9 to 45 years old. Many other countries allow men and women over the age of 26 and even over the age of 45 to receive the nine-valent vaccine in private hospitals. Zhang Jun analyzed that due to late development, late launch, and lack of research data, the scope of application of the nine-valent vaccine in the mainland has been subject to stricter controls.

Zhang Jun explained that the previous clinical data of Merck’s nine-valent vaccine in East Asian populations were concentrated in 16 to 26 years old, which is why people beyond this age group have not yet been approved for vaccination in the mainland. “But this does not mean that in other age groups The nine-valent vaccination does not have a protective effect." Wei Lihui, chairman of the Colposcopy and Cervical Cancer Pathology Branch of the Chinese Society of Eugenics Sciences (CSCCP), said that my country is currently conducting clinical trials of HPV preventive vaccines on diverse populations, including clinical trials of the marketed nine-valent vaccine to expand age groups and young men. , some domestic HPV vaccines are also entering the clinical trial stage. Zhang Jun added that as long as you regulate your sexual life after vaccination and pay attention to protection, postponing subsequent vaccinations will not have much impact on the protective effect.

However, many studies have proven that the earlier the vaccination, the better the protective effect of the HPV vaccine. In March 2022, a study published in "Vaccine", a journal of Nature Publishing Group , pointed out that the performance of related antibodies in adolescents aged 10 to 14 after vaccination with the HPV vaccine was generally better than that in adults aged 18 to 53, which means The HPV vaccine can produce better protection among adolescents. At the same time, studies have found that adolescent vaccine recipients have stronger persistence of binding antibodies than adults. WHO also recommends that girls aged 9 to 14 should be given priority for vaccination. "Don't delay vaccination just to wait for the 9th price. The protection power of the 2nd and 4th price is sufficient." Wei Lihui told China News Weekly.

The difference in the approved population at home and abroad makes many people over the age of 26 willing to pay high prices to go abroad to receive the nine-price vaccine. Last year, Xiao Lin, who worked as a market analyst at the Japanese headquarters of a cross-border trading company, finally got his appointment at a private hospital in Tokyo after more than two months of waiting. She originally thought that all the vaccinators were Japanese, but she and "more than a dozen vaccinators started chatting in Chinese" - her opponents who were competing for the nine-price vaccine were still Chinese who couldn't get the vaccine.

But even overseas, hospitals are still cautious about the nine-valent vaccine. Merck mentioned in the “HPV Vaccination Recommendations” published on its official website: “All children 27 to 45 Adults under the age of 30 should have a joint decision-making discussion with clinicians to determine whether they should receive the nine-valent vaccine. The U.S. Centers for Disease Control and Prevention (CDC) explains that most adults in this age group have been infected with HPV, and the vaccine can provide Protection is more limited than for people aged 9 to 26. "The HPV vaccine can only prevent new infections, but it cannot treat existing infections." Before the vaccination, Xiao Lin was also told many times by Japanese doctors that due to the late launch, the test results of the nine-valent vaccine can only guarantee an effective protection period of more than 7 years. ·

Not only for women, studies have also proven that the HPV quadrivalent vaccine and the nine-valent vaccine also have a protective effect on men. The US CDC earlier related research found that HPV types 6 and 11, which are covered by the quadrivalent vaccine, are the main culprits that cause 90% genital warts in both men and women. However, the "Recommendations for the Use of HPV Vaccine in Children and Adolescents" updated in 2018 by the Canadian Pediatric Society and the Committee on Infectious Diseases and Immunization pointed out that compared with the quadrivalent vaccine, men will not benefit much from the other five serotypes of the nine-valent vaccine. After all, These five viruses cause less than 1% of oropharyngeal cancers.

In 2015, the Immunization Implementation Advisory Committee under the US CDC recommended that the nine-valent HPV vaccine be included in the national immunization plan. A year later, the CDC removed bivalent and quadrivalent vaccines from the purchase list. The CDC explained that this is because the incidence rate of genital warts in the United States is higher than that of cervical cancer, and purchasing the nine-valent vaccine is a choice that suits the national conditions. Moreover, this is also related to the degree of economic development of the United States itself.

In addition to several existing HPV vaccines, domestic 11-valent, 14-valent, and 15-valent HPV vaccines are currently under development. As one of the developers of the 15-valent HPV vaccine in China, Liaoning Chengda Biological Co., Ltd. introduced that the 15-valent vaccine can prevent all high-risk types and HPV viruses related to genital warts on the basis of nine prices. Zhang Jun revealed: "It is expected that in the next 2 to 4 years, we may see the domestic nine-price cervical cancer vaccine on the market. Within 10 years, a higher-priced vaccine is also likely to be available."

Vaccination does not mean the end of prevention and treatment

July 2020, Harvard School of Public Health Author Emily Hamburg and others analyzed 48 countries that received assistance from the Global Alliance for Vaccines and Immunization (Gavi) and found that the bivalent HPV vaccine with cross-protective effect was effective in 63% to 83% of low- and middle-income people. It is more cost-effective than the nine-price in the country. Research by

Hamburg and others has deduced such a set of data: By 2100, when the vaccination rate in 48 Gavi-aided countries reaches 70%, bivalent vaccines with cross-protective effects can prevent 17.2 million cases of cervical cancer. This is equivalent to the 18.5 million cases avoided by price nine.

"Most countries with centralized procurement and public immunization programs spend no more than $30 per dose of HPV vaccine." Eduardo Franco, chair of the Department of Cancer Epidemiology and Chair of the Department of Oncology at McGill University School of Medicine in Montreal, Canada, described the vaccine Distribution is regarded as an economy of scale. As long as the coverage rate is higher, the unit cost of can be reduced through centralized procurement.

However, with supply exceeding demand, significant price cuts may only await the arrival of the "patent cliff". Lin Yuancheng, deputy director of the Domestic Patent Department of the Patent and Trademark Office of the China Council for the Promotion of International Trade, told China News Weekly that the so-called "patent cliff" refers to the sales of pharmaceutical factories and related commercial institutions once the patent expires and the technology and products are copied on a large scale. and profits will drop sharply.

From 2006 to 2008, this was the first blowout period for different institutions and manufacturers to apply for HPV vaccine-related patents in China.The study found that 43% of the world's HPV vaccine-related patents were filed in China, with the United States ranking second, accounting for 28%. The "Patent Law of the People's Republic of China" stipulates that the term of invention patent rights is 20 years. This also means that by 2026 to 2028, a large number of HPV vaccine-related patents will expire.

However, completing the HPV vaccine does not mean the end of prevention and treatment. A patient who develops cervical cancer due to HPV infection will live like a healthy person for the first ten or even twenty years. In 2003, the Cervical Cancer Prevention Alliance jointly established by eight international public health organizations published a "Cervical Cancer Prevention Fact Sheet", which pointed out that cervical precursor lesions produced by persistent infection with high-risk HPV usually develop into cancer. 7~20 years. Once the disease period has passed, patients may find that their vagina begins to have contact bleeding one day, and they often experience pain in the lumbosacral region.

But few people care about the changes in their bodies at this stage. Most HPV infections are sexually transmitted, and the lack of confidentiality about "sex" causes many women to miss the best opportunity for cervical cancer screening.

"Women who have sex have an 80% chance of being infected by HPV in their lifetime. This is not a matter of style, but a normal and common phenomenon." Wei Lihui told China News Weekly, "Cervical cancer is not like most other cancers. , it is possible to detect html through regular screening 2 Precancerous lesions , and can be effectively prevented through active treatment. Therefore, it is also necessary to eliminate the stigma and build people’s awareness of regular screening. ”

In Italy, all women aged 25 to 64 will be screened every 3 years. I received an email from the National Health Service. It states the procedures for cervical cancer smear testing, when and where to take it. Similarly, the "Guidelines for the Prevention and Early Detection of Cervical Cancer" revised by the American Cancer Society on April 22, 2021, recommends that cervical cancer screening should start at the age of 25 and be performed every 5 years. The National Cancer Center of Japan has advanced the age of cervical cancer screening to 20 years old and increased the frequency to once every 2 years.

Achieving a cervical cancer screening rate of 50% for women of appropriate age by the end of 2025 is a short-term goal set by the National Health Commission . In 2021, the "Cervical Cancer Screening Work Plan" released by the National Health Commission shows that domestic cervical cancer screening targets will cover women aged 35 to 64 years old.

This is not an easy goal to achieve. Wei Lihui believes that the first priority is to ensure the screening of women who are in the peak period of cancer between 35 and 45 years old. But for individuals, as soon as they start having sex, it is best to do regular screenings on their own. Even if adult women have received the HPV vaccine, screening is still important. After all, there is a possibility of being infected with the virus before vaccination.

According to WHO recommendations, by 2030, global cervical cancer screening coverage for adult women should reach 70%. This number was mentioned again in the implementation plan of China’s Women and Children’s Development Program for 2021-2030 issued by the National Health Commission in April this year. Qiao Youlin, director of the Cancer Epidemiology Research Office of the Cancer Institute of the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, mentioned in an interview with the media that "if this number is not reached, the control of the disease will be negligible."

(At the request of the interviewee, Wang Han, Liu Si, and Xiao Lin are all pseudonyms in the article)

Published in the 1050th issue of "China News Weekly" magazine on July 4, 2022

Magazine title: The snapped-up HPV vaccine

Author: Zhou Xinyu

Source: China News Weekly