Does hpve-9 vaccine have to be given before the age of 26?

Beijing, 22 Mar (Xinhua) -- On 22 March, xinhua daily telegraph published a report entitled "Repeatedly deceived by high-priced scalpers to grab seedlings, and going overseas for vaccination at any cost of time and money: Do we have to rush to the age of 26 to receive the HPV nine-valent vaccine?" report.

"500 nine-valent HPV vaccine quotas!" What a 'fairy' school this is! One interviewee wrote in the circle of friends.

On March 8 this year, the 112th International Women's Day, Zhejiang University launched a special appointment for the nine-valent vaccine to enter the campus for women's health activities, and 500 nine-valent HPV (human papillomavirus) vaccination quotas were open to all female students aged 16 to 26 at Zhejiang University. It is reported that this activity is voluntary self-funded vaccination, the vaccination price is 1298 yuan / needle + 28 yuan vaccination fee / time, the whole process of vaccination three injections, the total cost of 3978 yuan, and the public hospital vaccination price is consistent.

The topic of "Zhejiang University celebrating Women's Day with nine prices" immediately exploded throughout the network, and a number of social media platforms "dominated the list" on the same day. Zhejiang University became the "top stream" on this day, which also reflects the continuous heat of the current nine-valent HPV vaccine market.

Many women of the right age lamented, "Why didn't I catch this 'fairy' school?" Some women who are about to turn 26 are anxious, and it is difficult to find a seedling with a price increase of more than a thousand yuan, and even some people accidentally planted into the "scam".

To get the HPV vaccine, must you "grab" the nine valence before the age of 26? What is the difference between the effect of bivalent and quadrivalent vaccines and the nine-valent vaccine? How can I avoid falling into the "trap" of online vaccination appointments? With these questions in mind, the Xinhua Daily Telegraph reporter launched an investigation.

On May 18, 2020, at the Hubei Provincial Maternal and Child Health Hospital, nurses injected a girl from Wuhan with a domestic HPV vaccine. Photo by Xinhua News Agency reporter Xiong Qi

Nine prices are difficult to grab, and traps are difficult to defend

At 1:30 p.m., Xiaoting secretly took out her mobile phone during class, opened the WeChat mini program of a private hospital, and lit "My Order" over and over again. After a dozen times, the words "to be paid" were finally revealed. Too late to check the order information, Xiaoting quickly paid, watching the words "successful payment" of the three-shot nine-valent HPV vaccine appear on the mobile phone screen, and a "big stone" in her heart could be regarded as falling to the ground.

Before she could exit the payment page, Xiaoting received a message from the Taobao merchant: "Has the payment been successful?" Don't forget to click to receive the goods! Xiaoting clicked "Confirm Receipt", and the 600 yuan vaccine rush fee was instantly credited into the merchant's account...

Xiaoting, a 21-year-old sophomore at a university in Beijing, is a 21-year-old from Wenzhou, Zhejiang Province, and she has included the nine-valent HPV vaccine on this semester's must-do list.

The HPV vaccine can prevent certain types of HPV infections, thereby reducing the probability of developing diseases such as cervical cancer, vaginal cancer, male penile cancer, male and female anal cancer in women. At present, there are three kinds of HPV vaccines on the market, bivalent, quadrivalent and nine valents, corresponding to the number of HPV types that can be prevented.

"I feel that the recent vaccine shortage is particularly serious, in the freshman year, the school hospital had a batch of nine-valent HPV vaccines, but I did not grab it." I have also tried to grab seedlings in public hospitals and private hospitals, but every time I have no results, I really have no way to find someone to grab on the Internet. Xiaoting talked about her experience.

The merchant that provides "snatching" services to Xiaoting is actually a "technical scalper", which can not only grab vaccines, but also grab concert tickets, train tickets and other tickets. Before the vaccine of the private hospital is released, the merchant and Xiaoting log in to the account of Xiaoting in the private hospital Mini Program at the same time, and after the merchant grabs the vaccine for the first time through technical means, the order information will appear synchronously on Xiaoting's mobile phone, and Xiaoting can pay.

"Even if I didn't grab it, the 600 yuan robbery fee will not be refunded, so I dare not gamble, but fortunately I won the bet." Xiaoting said.

Xiaoting received three injections of nine-valent HPV vaccine, with a total price of up to 5680 yuan. The reporter opened an HPV vaccine appointment mini program and found that the three-shot nine-valent HPV vaccine in private hospitals was generally between 5300 and 6400 yuan, and they were out of stock.

The reporter inquired about the relevant situation of the nine-valent HPV vaccine at a community health service center in Xicheng District, Beijing, and the reply was that the price per injection was 1323 yuan, no need to increase the price, but the earliest appointment time for vaccination was In May 2023, and the household registration of the vaccinator must be in the community.

At present, the nine-valent HPV vaccine is suitable for women aged 16 to 26 in the mainland. In online channels such as the national government service platform, many women who are about to turn 26 have "complained" about their experience of grabbing seedlings, including many deceived.

Seeing that she was about to be 26 years old, Xiao Dai was a little anxious, "Making a community phone appointment, every time I was told that there was a shortage of seedlings, and I grabbed seedlings on the App several times, but every time it was 'second light'..."

In desperation, Xiao Dai searched for an intermediary who claimed to be able to contract vaccines on Weibo. "The other party promised to pay a deposit of 500 yuan to help with the contract, and then pay the full amount after the contract was successful, and after a week, it could be arranged to be vaccinated at a nearby community health service center." Xiao Dai didn't think much about it, and after paying the deposit, she received a successful sms for the appointment prefixed with "medical deer", and then paid off the balance of more than 4500 yuan.

When Xiao Dai sent the screenshot of the payment to the intermediary, the other party began to "find fault". "Saying that I did not note the 'name + balance' when I paid, the background could not recognize and match the seedlings, and promised that it would be refunded automatically within one hour, and asked me to pay again."

Xiao Dai, who was eager to ask Miao, transferred another 4500 yuan according to the requirements of the other party. She kept urging the other party to refund the money, but the other party disappeared. Xiao Dai realized that she had been deceived.

After Xiao Dai posted the deception to social media, she did not expect that there were not a few people with similar experiences, and some people were even cheated of more than 30,000 yuan.

"I've seen bloggers on the Internet share cases of themselves asking scalpers to inoculate on behalf of others. Thinking that the blogger has been successfully vaccinated, she contacted the scalper according to her method, and was cheated of nearly 10,000 yuan, which found that the blogger and the scalper were in the same group. Wenwen, 25, revealed to reporters.

A friend once suggested that Wenwen go to Hong Kong or Macao for vaccination, "the nine-valent vaccine should be given three injections, several round-trip, transportation and accommodation costs are not low, coupled with the impact of the epidemic, I still choose to vaccinate locally, but I did not expect so many traps." Wenwen said with chagrin.

Behind the phenomenon of seedling seekers is the concern about HPV infection. The Expert Consensus on Immunoprophylaxis of Papillomavirus-related Diseases of Cervical Cancer and Others (Simplified Version) (hereinafter referred to as the Consensus) published in the Chinese Journal of Epidemiology in December 2019 proposes that the occurrence of cervical cancer is an occasional event after HPV infection.

The Consensus mentions that the vast majority of HPV infections are asymptomatic transient infections that can histologically present as low-grade cervical lesions, and that more than 80% of infections can be cleared by the body within 6 to 24 months. More than 60% of low-grade lesions will naturally improve, and only about 1% of low-grade lesions can progress to cervical cancer. Usually HPV infection takes 10 to 20 years of natural evolution to develop into cancer.

"The sooner the better, not the more expensive the better"

"If you want to get a nine-valent vaccine", "I'd rather spend more money and improve the vaccine's protection against the virus"... The reporter's investigation found that many young women generally choose "high or low" when they receive the HPV vaccine.

According to public information, about 200 hpvic types have been identified from the human body, which are divided into high-risk and low-risk types according to carcinogenic potential, and high-risk types include HPV16/18/31/33/35/39/45/51/52/56/58/59/68, a total of 13 types. Among them, HPV16/18 is "in danger". Studies have shown that bivalent, quadrivalent and nine-valent vaccines are essentially equal in preventing HPV16/18 infection.

Taking cervical cancer as an example, it can be divided into squamous cell carcinoma and adenocarcinoma according to the type of pathology. The results of two studies in China showed that among patients with cervical squamous cell carcinoma, the high-risk hpvic infection rate was 97.6%, and HPV16/18 was the most common type, with a total infection rate of 84.5%; among patients with cervical adenocarcinoma, the high-risk HPV infection rate was 74.5%, and HPV16/18 was also the most common type, with a total infection rate of 65.7%.

The Consensus mentions that three imported HPV vaccines (GlaxoSmithKline bivalent HPV vaccine in the United Kingdom, Merck quadrivalent HPV vaccine in the United States, and Merck nine-valent HPV vaccine in the United States) can provide high protection against HPV16/18. Moreover, bivalent and quadrivalent HPV vaccines provide some degree of cross-protection against high-risk HPV other than HPV16/18, especially HPV31/33/45. The domestic bivalent HPV vaccine approved for marketing in December 2019 also has a strong lasting protective effect on HPV16/18.

"For HPV vaccination, it is recommended that the sooner the better, not the more expensive the better." Zhang Yu, director of the Department of Obstetrics and Gynecology at Xiangya Hospital of Central South University, said.

Studies have also shown that the antibody titers (used to measure the minimum concentration required for an antibody to recognize the deciding site of a particular antigen) in women aged 9 to 17 years old after receiving the bivalent HPV vaccine are 2 to 3 times higher than those in women aged 18 to 25 years. The antibody titers of women aged 9 to 15 years after receiving the quadrivalent HPV vaccine can reach 1.4 to 2.8 times that of women aged 16 to 26 years.

Zhang Yu also reminded that many people think that after receiving hpvvic vaccine, they no longer have to worry about cervical cancer, but this is not the case. Women who have been vaccinated still need to be screened for cervical cancer regularly to further reduce the incidence of cervical cancer. On the one hand, some women may have been infected with HPV when they were vaccinated, and on the other hand, the HPV vaccine does not cover all high-risk types of HPV infection.

"Vaccinations are no longer recommended for people over 45 years old, and it's especially important to stick to screening." Zhang Yu said.

Where did the 26-year-old threshold come from?

Due to the idea that "nine-valent HPV vaccine must be vaccinated before the age of 26", many women who are about to turn 26 years old would rather spend high prices to find scalpers to vaccinate with nine prices than to vaccinate bivalent and quadrivalent in formal channels. The latter two vaccines are for women aged 9 to 45 years and women aged 20 to 45 years.

What's more, the bivalent vaccine has been vaccinated and it is still hoped that the nine-valent vaccine can be re-injected before the age of 26 in order to strengthen the preventive effect. "What should I do if I can't get vaccinated after the age of 26?" It has become a problem for many people.

The reporter checked the data and found that some nine-valent HPV vaccines in the United States, Hong Kong and other countries and regions are applicable to the age range of vaccination is not 16 to 26 years old, but 9 to 45 years old can be vaccinated. Therefore, there are also many women over the age of 26 who do not hesitate to take more time and money to go overseas to get the nine-valent HPV vaccine.

Merck, the manufacturer of the nine-valent HPV vaccine, mentions in the "HPV Vaccination Recommendations" published on its website: "The nine-valent HPV vaccine is recommended for all boys and girls aged 11 or 12 years (but can start at the age of 9), as well as for those who have not been vaccinated or have not been adequately vaccinated before the age of 26. All adults aged 27 to 45 should have a joint decision discussion with a clinician to determine whether they should be vaccinated. ”

This means that among the vaccination recommendations given by merck's official website, 9 to 45 years old can be vaccinated with the nine-valent HPV vaccine. It is worth mentioning that the reporter checked the instructions for the nine-valent HPV vaccine listed by Merck in the mainland but found that "this product is suitable for vaccination of women aged 16 to 26 years old".

So how exactly is the age limit of 16 to 26 years old determined? The reporter found the "Technical Review Report on the Application for Listing of the Nine-Valent Human Papillomavirus Vaccine (Saccharomyces Cerevisiae)" (JXSS1800008/9) issued by the Drug Review Center of the State Food and Drug Administration in October 2018 after the Merck 9-valent HPV vaccine was approved for marketing in the mainland, which made the following explanations:

"The application for import registration of this product is based on overseas clinical research data and has not been clinically tested in China. In accordance with the spirit of Circular No. 42 of the General Office of the CPC Central Committee and the General Office of the State Council, consider supporting the import registration of this product with overseas clinical research data. The global clinical trial data of this product basically confirm the consistency of safety, immunogenicity and protective efficacy between the East Asian population and the total population, and it may be considered to conditionally approve the domestic listing of this product based on overseas data.

"In view of the current overseas clinical data of this product, the evidence for the low age group of the East Asian population (especially the Chinese group) is still insufficient, coupled with the fact that the sexual life of women in mainland China is later than that of Western countries, taking into account many factors such as health economics, it is tentatively determined that women aged 16 to 26 years old are suitable for the vaccination population of this product, and the applicant submits domestic clinical trial data to fully prove the effectiveness and safety of this product in the low age group, and then update the instructions."

The age of application for the nine-valent HPV vaccine was thus determined in the Mainland and continues to this day. At the same time, the note also means that the applicable age of 16 to 26 years old is not unchangeable, at least with the accumulation of domestic clinical trial data, it is possible to achieve the nine-valent HPV vaccine before the age of 16.

In fact, trials of the nine-valent HPV vaccine against a wider age range of mainland women are being carried out in an orderly manner. According to public information, Merck has conducted a Phase 3 open clinical study entitled "Evaluation of the Immunogenicity and Safety of The Nine-Valent Human Papillomavirus Vaccine (V503) in Chinese Women Aged 9 to 45 years" in March 2019, which plans to recruit a total of 1,990 mainland women to participate in the trial, with the aim of testing the safety of the company's nine-valent HPV vaccine among mainland women aged 9 to 45 years.

The recruitment of subjects for this study has now been completed and trials are underway.

Bivalent free vaccinations are on the way

At the two sessions of the National People's Congress this year, the vaccination of HPV vaccine and the prevention and treatment of cervical cancer were hotly discussed by deputies, and a number of people's congress deputies have submitted suggestions on free HPV vaccination for women of appropriate age. Xu Ping, a deputy to the National People's Congress, suggested that the domestic bivalent HPV vaccine be included in the immunization program; Cai Weiping, a deputy to the National People's Congress, suggested that non-immunization program vaccines, including HPV vaccines and rabies vaccines, be included in the scope of payment by amending the social insurance law.

According to data released by the International Agency for Research on Cancer in 2021, there were 604,000 new cases of cervical cancer worldwide in 2020, of which nearly 110,000 were in China. In 2020, there were about 342,000 deaths of cervical cancer worldwide, and nearly 60,000 in China. In the past 20 years, the incidence and mortality of cervical cancer in China have shown an increasing trend year by year, and they tend to be younger.

The birth of the HPV vaccine makes cervical cancer hope to become the first malignancy that can be completely eliminated in humans. As of January 2020, more than 104 countries and territories around the world have included HPV vaccines in national immunization programmes. At present, HPV vaccines are still classified as non-immunization programme class II vaccines in the mainland, and vaccinators follow the principle of "informed consent and voluntary self-payment".

In 2019, the National Health Commission and 10 other departments jointly formulated the "Healthy China Action - Cancer Prevention and Control Implementation Plan (2019-2022)", which clearly stated that it is necessary to promote the scientific publicity of HPV vaccination and promote the vaccination of people of the right age. Accelerate the review and approval process of domestic HPV vaccines and improve the accessibility of HPV vaccines. Through price negotiation, centralized procurement, etc., promote HPV vaccine supply enterprises to reasonably set prices, and explore various channels to ensure the vaccination of age-appropriate people in poor areas.

Since 2020, the free vaccination of domestic bivalent HPV vaccines is being carried out in many parts of the country, and inner Mongolia, Fujian, Shandong, Sichuan, Jiangsu, Hainan and other places have successively carried out this work.

The National Health Commission said China will fully support the World Health Organization's Global Strategy to Accelerate the Elimination of Cervical Cancer, which makes it clear that by 2030, 90% of girls in the world will complete HPV vaccination by the age of 15. Through tertiary pathways of vaccination, screening and treatment, we will promote the global goal of eliminating cervical cancer.

In response to the persistent high price and shortage of imported HPV vaccines, Wu Ting, a professor at the School of Public Health of Xiamen University, said that the domestic bivalent HPV vaccine "Xinkenin" is produced using an independent and innovative E. coli technology platform, making it possible to produce vaccines on a large scale at a lower cost.

In 2021, "Xinkoning" passed the pre-certification of the World Health Organization, which means that domestic HPV vaccine products have the opportunity to enter overseas markets for procurement by the UN system. The nine-valent HPV vaccine developed by xiamen university team has also entered phase III clinical trials, and it is expected to obtain preliminary efficacy data in 2023 and is expected to be available in 2023 or 2024.

(Xiao Ting, Xiao Dai and Wen Wen are pseudonyms)

(Contributors: Zhang Silin, Liu Chen, Zhang Yiran)