The website of the State Food and Drug Administration announced on August 30 that the indications of Merck's nine-valent human papillomavirus vaccine (Saccharomyces cerevisiae) (hereinafter referred to as nine-valent HPV vaccine) have been expanded, and the age of HPV nine-valent vaccine has been expanded to 9-45 years old. Previously, the applicable age was 16-26 years old.
This means that my country's bivalent, quadrivalent, and nine-valent HPV vaccination coverage has been extended to women aged 9-45.
Has the age-expanded nine-valent HPV vaccine opened the prelude to appointment vaccination?
The Red Star News reporter learned from an interview that so far, including Zhejiang, Shanghai and other places, no appointments have been opened, and some areas said that they still have to wait for more than a month before the new nine-valent vaccine arrives.
In the opinion of many experts, with the expansion of the age of the nine-valent vaccine, the situation of "one vaccine is hard to find" may intensify in the short term.
In this regard, the Red Star News reporter interviewed a number of obstetrics and gynecology experts, immunology experts and vaccine experts, and made a detailed interpretation of the basis and utility of the age-expanding nine-valent HPV vaccine, the follow-up impact on the market, and the safety of vaccination.
4 years since HPV vaccine entered the Chinese market
Penetration rate is still low, vaccination demand has not been met
HPV, the human papilloma virus, is one of the main "culprits" that cause cervical cancer in women.
The Red Star News reporter checked relevant information and found that among female malignant tumors, the incidence of cervical cancer is second only to breast cancer.
Relevant data show that more than 90% of cervical cancers are caused by high-risk HPV infection.
According to statistics, there are more than 200 HPV subtypes that have been isolated, of which 16 and 18 have the highest risk of inducing cancer, and at least 14 can lead to cervical cancer or other malignant tumors.
But being infected with HPV does not necessarily mean that you will develop cervical cancer.
Data show that more than 80% of women have at least one HPV infection in their lifetime, more than 90% of HPV infections can be cleared naturally within 2 years, and less than 1% of patients will develop cervical precancerous lesions and cervical cancer.
Therefore, early interventional screening, prevention and post-infection treatment are particularly necessary.
Therefore, since the world's first HPV vaccine was launched in 2006, many countries have gradually realized the importance of vaccination. For example, in 2014, the HPV vaccine was approved for marketing in the United States; on April 28, 2018, the State Drug Administration announced that The nine-valent HPV vaccine, which is conditionally approved for cervical cancer prevention, has also been launched in China.
As the world's first vaccine that can be used to prevent cancer, HPV vaccine has always attracted the attention of age-appropriate vaccination groups, and related vaccines have also entered the market in my country.
Up to now, five HPV vaccines have been approved for marketing in my country, including three imported vaccines and two domestic vaccines.
Among them, the imported vaccines are GlaxoSmithKline's bivalent HPV vaccine, Merck's quadrivalent HPV and nine-valent HPV vaccines, and domestic HPV vaccines include Wantai Bio's bivalent HPV vaccine and Watson Bio's bivalent HPV vaccine.
However, due to the short period of time since the introduction of HPV vaccine in China, although the number of batches has grown rapidly, the penetration rate is still at a low level, and the demand for vaccination is far from being met.
According to the "2018-2020 Estimated Vaccination Rate of Human Papillomavirus in Chinese Women Aged 9-45" published last year by Song Yifan and other 9 people from the Immunization Planning Center of the Chinese Center for Disease Control and Prevention, 2018-2020 Chinese women aged 9-45 years old A total of 21,597,400 doses of HPV vaccine have been vaccinated, and the cumulative estimated vaccination rate is only 2.24%. Even the highest in Beijing, Shanghai, and Zhejiang provinces are only 8.28%, 7.37%, and 4.68%, respectively.
Multiple medical institutions:
Expansion vaccinations will have to wait
At present, a certain period of time has passed since the release of the news of the age expansion of the HPV nine-valent vaccine.
Has the expanded vaccine been on the market?
The Red Star News reporter learned that places such as Shanghai, Henan, Zhejiang and other places have not yet opened the vaccination service for age-expanding vaccines.
In Zhejiang, the reporter inquired about the "Zheli Office" on August 31 and found that most of the recent nine-valent vaccine reservation lotteries still indicate that only women aged 16-26 can participate.
The staff of the Zhejiang Provincial Center for Disease Control also told reporters that when women aged 9-45 can be vaccinated depends on when the outpatient clinic can get the vaccine with the updated instructions.
Therefore, it will take some time for the newly approved age group to be able to receive the nine-valent vaccine.
In Shanghai, many local community health service centers also gave similar answers to Red Star News reporters.
"We haven't received a notice to start an appointment for women aged 9-45, and we can make an appointment for vaccination after receiving the notice." The Obstetrics and Gynecology Hospital Affiliated to Fudan University also stated on the social platform that the hospital has not yet received the nine-valent vaccine. Age Expansion Notice.
It is understood that at present, whether it is imported quadrivalent or nine-valent HPV vaccine in Shanghai, it is necessary to make an appointment in advance. The shortest waiting time takes a few months, and the long one even takes 1-2 years.
The same situation also appeared in Henan.
A reporter from Red Star News randomly called a community health center in Zhengzhou, and an operator told the reporter that the news of the age-expansion of the nine-valent HPV vaccine was newly released, so most local health centers have not yet received relevant notifications from higher-level departments.
The staff member said that at present citizens other than 16-26 years old are still unable to receive the nine-valent HPV vaccine, and it is expected that a new batch of Merck's nine-valent HPV vaccine will arrive in more than a month.
What is the basis for age expansion of HPV nine-valent vaccine?
Experts: have undergone experimental research and expert demonstrations
Even if it still takes time, the advent of an age-expanding vaccine is a certainty.
So, with the extension of the vaccination period of the HPV nine-valent vaccine, can the vaccination penetration rate in my country be effectively improved?
Can the current situation of "one seedling is hard to find" in the market be alleviated?
On the basis of the expansion of the age of the HPV nine-valent vaccine, does it mean that the bivalent and quadrivalent vaccines are no longer necessary?
With these questions, the Red Star News reporter talked to a number of obstetricians and gynecologists, vaccine experts and immunology experts.
The Red Star News reporter checked the public information and found that the World Health Organization (WHO) had recommended that girls aged 9 to 14 who have not had sex should be the primary vaccination targets, and that two injections in this age group should be enough.
As for women over the age of 26, the WHO has also stated that the recommended age for vaccination by the US Centers for Disease Control and Prevention is 9-26 years old; it is not generally recommended for women over 26 years old, but if you still want to be vaccinated, you can discuss with your doctor.
However, the American Cancer Society clearly does not recommend the HPV vaccine for people over the age of 26.
So why did most countries, including China, strictly limit the age of 9-valent vaccines to 16 to 26 years old in the past?
Gong Xiaoming, a doctor of medicine at China Union Medical College and a freelance doctor of obstetrics and gynecology, explained that in the early stage of vaccines entering China, due to lack of research data, only 16-26 years old were approved according to international practice.
With the results of more age-stage studies showing that the safety and effectiveness of the nine-valent vaccine are guaranteed, my country has only approved the age expansion of the nine-valent vaccine.
An immunologist who did not want to be named told Red Star News: "The probability of the newly launched age-expanded vaccine is the same as in the past, but the application of the vaccine has been expanded through the application of the enterprise." The immunologist said, Such applications are also in line with national standards, rather than "take it for granted".
He pointed out that whether the vaccination age can be expanded depends on experimental research, expert demonstration, review and approval by relevant state departments, and certification of a series of experimental data before the vaccine can be expanded to the applicable age range.
Vaccine expert Tao Lina also told the Red Star News reporter that the expansion of the age of the HPV9 vaccine or the certification of new indications requires approval for marketing, which must also be fully verified by clinical research to confirm its protective effect and safety. to be approved.
In Tao Lina's view, the approval of new age-appropriate groups by my country's drug regulatory authorities must also be based on clinical validation of similar groups.
As the world's first company to launch quadrivalent and nine-valent HPV vaccines, Li Zhengqing, its global senior vice president and president of Merck's China R&D Center, also publicly stated that the expansion of the nine-valent HPV vaccine indication age group is Merck's promotion of vaccine research and development innovation. another important milestone.
He said that Merck has been exploring the potential of HPV vaccine to prevent various diseases in different populations based on rigorous clinical research and a large amount of real-world data over the years.
"We are currently conducting a number of clinical studies on new indications for HPV vaccines in China, hoping to help more people benefit as soon as possible in the future."
Nine-valent vaccine and one "vaccine" are hard to find
Experts recommend that people over 26 years old get low-cost vaccines first
Gong Xiaoming told the Red Star News reporter that there are currently three types of HPV vaccines launched in China, one is bivalent, mainly for 16 and 18 subtypes, accounting for about 70% of the incidence of cervical cancer.
The quadrivalent vaccine increases immunity against HPV subtypes 6 and 11.
The nine-valent vaccine is currently the most widely covered subtype of HPV, including subtypes 6, 11, 16, 18, 31, 33, 52, 58, and 45, which can cover more than 90% of cervical cancer. related viruses.
Relevant data also show that more than 90% of cervical cancers are caused by high-risk HPV infection.
There are more than 200 subtypes of HPV viruses, of which types 16 and 18 have the highest risk of cancer induction.
There are currently bivalent, quadrivalent and 9-valent vaccines for cervical cancer.
"Valence" represents the number of virus subtypes that can be prevented. The bivalent for types 16 and 18 can prevent more than 70% of cervical cancers, and the nine-valent HPV vaccine can prevent about 90% of cervical cancers.
So, with the expansion of the 9-valent vaccine with the highest coverage rate, does it mean that the bivalent and quadrivalent vaccines will be "no one cares"?
To this, Taurina gave a negative answer.
He pointed out that despite the age expansion of the nine-valent vaccine, there is a high probability that Merck will not increase its production capacity because of this, but with the trend of age expansion, the number of people who choose nine-valent vaccines will inevitably increase, and the situation of "one vaccine is hard to find" will be in a short period of time. The probability of occurrence will increase.
"The main significance of age expansion is that our choices have increased, but it will also cause some groups who missed the age of nine prices to continue to wait for nine prices, which will result in delayed vaccination." For this phenomenon, Tao Lina believes that it is better to The plan is to make two or four prices first, and replant after the nine prices are fully rolled out, so as not to delay the best time for vaccination.
In order to achieve the complete elimination of cervical cancer by the end of this century, WHO has set a phased goal for 2030 in the "Global Strategy for Accelerated Cervical Cancer Elimination", including 90% of girls in 2030 to complete the full course of HPV vaccination before the age of 15.
But the reality is that my country's current HPV vaccine coverage is low.
According to the statistics of the "Guangdong Expert Consensus on the Application of HPV Vaccine to Eliminate Cervical Cancer" released in September 2021, the vaccination rate of Chinese adolescents is less than 3%, and the vaccination rate of the whole population is less than 6%.
The inability to make an appointment for the HPV vaccine in a short period of time is one of the major reasons why the vaccination rate cannot be rapidly increased.
According to data from the National Routine Vaccine Statement, from 2018 to 2020, the number of HPV vaccinations rose from 3.417 million in 2018 to 12.279 million doses in 2020.
However, compared with the huge number of school-age women, the current HPV vaccine is still in short supply.
Therefore, Tao Lina believes that bivalent and quadrivalent vaccines can still play a good role in preventing high-risk HPV infection of cervical cancer, and at the same time can play a supplementary role in the process of vaccine shortage. There is still a necessity in the market behind it. , and will not immediately withdraw from the market in a short period of time.
So, can vaccines of different valences be mixed and vaccinated?
The above-mentioned immunologists pointed out that if all the previous HPV vaccines have been vaccinated according to the standard procedure, they hope to receive the nine-valent HPV vaccine. For this product, the inoculation of this product can only be started after an interval of at least 12 months, and the number of inoculation doses is 3 doses.”
However, as for whether the 9-valent vaccine can be vaccinated after the bivalent HPV vaccine is completed, the immunologist said that there is no clinical data to support it.
Are there any side effects after HPV vaccination?
Expert: side effects are small, even basically negligible
The role of HPV vaccines in the prevention of cervical cancer has been confirmed by multiple data, but most experts believe that even if vaccinated, it does not mean that it is completely "insulated" from cervical cancer.
"Data show that the first batch of vaccinated people in 2006 still have high titers, and no booster vaccination is needed, but vaccination cannot completely prevent other unprotected HPV subtypes from being infected." The above immunologists pointed out that even in the After receiving the HPV vaccine, cervical TCT and HPV screening should still be performed regularly.
"I personally recommend that all women who have had sex, whether or not they have been vaccinated against HPV, need to undergo regular cervical cancer screening to nip cervical cancer in the bud in time," the immunologist said.
Gong Xiaoming also said that vaccination belongs to primary prevention, but it does not mean that women will not get cervical cancer at all.
"Because there may be infection before vaccination, and there may be subtypes that are not covered. Therefore, as an obstetrician and obstetrician, I think that even if vaccination is vaccinated, it is necessary to do regular cervical cancer screening and complete secondary prevention work. "
So, does the HPV vaccine work for any group?
Can its safety be guaranteed?
In this regard, Gong Xiaoming pointed out that the cervical cancer vaccine is relatively safe at present. From the analysis of research data on a global scale, its side effects are small and even negligible. Therefore, it is still recommended that women and men of appropriate age be vaccinated.
The above-mentioned immunologists also mentioned that, at present, except for very few cases of serious adverse reactions such as allergic reactions, no HPV vaccine has been found to have obvious harm to the human body.
The HPV vaccine is a non-programmed immunization vaccine, and people can choose to be vaccinated according to their specific circumstances, and the vaccinated population is not limited to women, but also men.
Previously, Andrea Carvalho, a senior scientist at the International Agency for Research on Cancer of the World Health Organization, once put forward: "More and more evidence shows that a single dose of HPV vaccine can have a good protective effect, and both boys and girls are vaccinated. The protective efficacy of the agent can reach 62%-70%, which can reduce costs, improve supply, and further achieve herd immunity.”
Red Star News reporter Yang Yuqi Hu Yiwen intern Xi Congcong reported from Beijing
Editor in charge Deng Yanguang, editor Guo Zhuang