Wen | Zhang Shuxia, a reporter of the "Finance and Economics National Weekly"
"Did you get the HPV vaccine?" In the past two years, many people will talk about this topic.
As the first cancer vaccine in human history, the birth of the HPV (human papillomavirus) vaccine has made cervical cancer the first malignant tumor that can be "eliminated".
At present, the HPV vaccines that have been listed in China are divided into three types: bivalent, quadrivalent and nine-valent. There are many choices, but people can't help but wonder: how much price is good?
In addition, most of the domestic population needs three injections to complete the whole process.
However, some time ago, the World Health Organization released news on its official website that a single dose of HPV vaccination can effectively prevent cervical cancer caused by persistent HPV infection, and the effect of two or three doses is comparable.
▲Screenshot of the official website of the World Health Organization
What's going on here?
The first cancer vaccine
When it comes to hpv vaccines, we must first talk about cervical cancer.
Cervical cancer is one of the most common gynecological malignancies. According to the Global Cancer Statistics Report released by the International Agency for Research on Cancer (IARC) under the World Health Organization, the number of new cases of cervical cancer in mainland China in 2020 will reach nearly 110,000, and the number of deaths will be about 59,000.
That is to say, on average, every 10 minutes, a woman on the mainland is killed by cervical cancer.
Moreover, from HPV infection to cervical cancer is a gradual development process, which generally takes several years or even more than ten years. This provides sufficient time for early detection, early prevention and early intervention of cervical cancer, which is conducive to reducing 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 defensive weapon - HPV vaccine. HpV vaccination is the best known means of prevention against cervical cancer and other lesions caused by HPV virus infection.
In countries and regions with high HPV vaccination coverage, hpV infection rates and cervical cancer rates have decreased significantly.
For example, the UNITED KINGDOM has included HPV vaccines in the National Immunization Programme (NIP) since 2008, providing routine vaccination with bivalent HPV vaccine for girls aged 12-13 and complementary vaccinations for women aged 14-18 years.
In November 2021, the authoritative medical journal The Lancet published a study based on the diagnosis data of cervical cancer and cervical precancerous lesions in 20-64-year-old women living in England in the 13-year period from 2006 to 2019, and found that the incidence of cervical cancer in women who received HPV vaccine showed a sharp downward trend. The researchers said the HPV vaccination program 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 the Elimination of Cervical Cancer in 2020, announcing that 194 countries, including China, will work together to achieve 90% of girls completing HPV vaccination by age 15 by 2030. According to the World Health Organization, 117 countries have now included HPV vaccines in their national immunization programmes.
Mainland China approved the first HPV vaccine on the market in July 2016, and there are currently three HPV vaccines on the domestic market: bivalent, quadrivalent and nine-valent.
The Outline for the Development of Chinese Women (2021-2030), issued in September 2021, proposes to promote pilot hpillomavirus vaccination among women of appropriate age.
▲Many places in the country have gradually promoted the universal vaccination strategy of HPV vaccine for women of appropriate age. Source: Guosen Securities Research Report
At present, many regions in the country have begun to provide free HPV vaccination for women of appropriate age or provide vaccination subsidies.
For example, as the first city in the country to start free HPV vaccination for people of the right age, Xiamen has been vaccinating girls aged 13 to 14 and a half years old free of charge with domestic bivalent vaccines since 2020.
Chengdu has adopted a more flexible subsidy policy, that is, for "female students aged 13-14 years old at that time", financial funds give 600 yuan / person vaccination subsidies, and parents of students can choose between domestic/imported bivalent and imported quadrivalent HPV vaccines.
Guangdong Province proposes to add about 600 million yuan for free HPV vaccination in 2022-2024, and free domestic bivalent HPV vaccine is given to girls under 14 years old who have a school registration in Guangdong Province, who have entered the first grade of junior high school since September and have not been vaccinated with HPV vaccine.
▲Guangdong propaganda poster for free HPV vaccination for school-age girls.
Wang Linhong, chief expert of 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 has changed from secondary prevention focusing on early screening to etiological prevention and early screening of HPV vaccine application, and prevention and control means have taken a qualitative leap.
It is better to chase "high" than to catch "early"
The benefits of HPV vaccination are self-evident, but the problem that many people are facing at present is that it is not easy to make an appointment for the last dose of vaccine.
According to the reporter of "Finance and Economics National Weekly", the imbalance between supply and demand of domestic HPV vaccines is prominent, the situation of "difficult to make an appointment" is common, and imported four-valent and nine-valent HPV vaccines are even more "difficult to find". The main reason is that the demand of the age-appropriate population is too large, and there is a huge gap in the supply of vaccines.
However, compared with imported vaccines that often wait for two or three years, domestic bivalent HPV vaccines are much more "friendly" to be booked, and most vaccination points can arrange the first injection within 1 month. However, many people who are willing to vaccinate still prefer to be able to label imported four- or nine-valent vaccines with higher prices and higher prices.
What does higher price mean?
As mentioned above, more than 95% of cervical cancer is caused by HPV, and there are currently more than 200 known HPV types, and technically, it is not possible to immunize all known HPV types, only a few of them can be selected.
The health risks posed by different types of viruses vary, and HPV is classified as high-risk and low-risk depending on carcinogenicity. According to the recommendations of the International Agency for Research on Cancer of the World Health Organization, the State Food and Drug Administration defines HPV16/18/31/33/35/39/45/51/52/56/58/59/68 as a high-risk type.
Among them, HPV16/18 has the highest risk of inducing cancer. Studies have shown that among cervical cancer patients, the HPV16 infection rate is 55.2%, and the HPV18 infection rate is 14.2%. That said, about 70% of cervical cancers are caused by these two high-risk types.
At present, the bivalent, quadrivalent and nine-valent HPV vaccines that have been listed in China have a good protective effect on these two high-risk types. In terms of the preventive effect of cervical cancer, there is almost no difference between bivalent and quadrivalent vaccines, and the protective efficacy is about 70%, but the quadrivalent HPV vaccine has two more low-risk types of HPV6 and HPV11, which increases the indications for preventing genital warts than the bivalent HPV vaccine. On the basis of quadrivalent HPV vaccine, five new high-risk types have been added, which is about 20% higher than the preventive and protective effect of bivalent and quadrivalent vaccines on cervical cancer.
▲Tabulation of this journal. Sources: vaccine specifications, listed company announcements, official websites of the State Food and Drug Administration, etc
Different vaccine prices do mean different protective effects. However, the age of vaccination is also affected by the effectiveness of vaccine protection.
To put it simply, the earlier people of the right age are vaccinated, the better the anti-cancer effect.
According to the statistics of the Lancet study on women vaccinated against HPV in the UK, the rate of cervical cancer and precancerous lesions declined the most among the youngest women vaccinated. Specifically, compared with the control cohort without HPV vaccine, the incidence of cervical cancer was reduced by 87% at age 12-13 years, the prevalence of vaccination at age 14-16 years was reduced by 62%, and the prevalence of vaccination at age 16-18 was reduced by 34% compared to the control cohort of those who were not vaccinated against HPV; in terms of cervical precancerous lesions (CIN3), the incidence of vaccination at 12-13 years was reduced by 75%, and the incidence of vaccination at 16-18 years was reduced by 39%.
The World Health Organization recommends that the hpv vaccine is primarily targeted for adolescent women who have not been exposed to vaccine-associated HPV genotypes. The U.S. Advisory Committee on Vaccine Immunization Practices and the U.S. Centers for Disease Control and Prevention recommend that HPV vaccination be started at age 11 or 12 years, or from age 9.
The "Chinese Expert Consensus on the Clinical Application of Human Papillomavirus Vaccine" issued by the Gynecologic Oncology Branch of the Chinese Medical Association and the Colposcopy and Cervical Pathology Branch of the Chinese Eugenics Science Association mentioned that women aged 13-15 years can maximize the benefits of HPV vaccination before the first sexual activity, and preferentially recommend hpv vaccination for women aged 9-26 years, especially women before the age of 17; and recommend that women aged 27-45 years receive HPV vaccine.
Because of this, many experts have called for the right age group to be vaccinated as soon as possible, and not to blindly wait for the "high" price vaccine and miss the best vaccination time.
"Compared with the high price and insufficient supply of quadrivalent and nine-valent HPV vaccines, bivalent vaccines have a higher cost performance for the prevention of cervical cancer." The Guiyang Municipal Center for Disease Control and Prevention said so.
Can a shot work?
Recently, many people have also paid attention to the recommendation of the World Health Organization on the official website of the HPV vaccine for a single dose.
Specifically, evidence for single dose HPV vaccination was considered at a meeting of the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization and concluded that a single dose hpv vaccination regimen is effective in preventing cervical cancer caused by persistent HPV infection and is comparable to that of two or three doses.
In this regard, the reaction gap between different groups of people is very large, just after the first injection, may be more happy, feel that the money of the next two injections has been saved; play the whole course, may feel that the loss, the back two injections are white; not yet on the appointment, then look forward to the back appointment can be easier, after all, the current domestic import of four-valent, nine-valent vaccine "one dose is difficult to find".
What are the facts? What is the basis for this discussion by the World Health Organization? Will the mainland HPV vaccination procedure change next?
First of all, many people understand this news as "one shot is enough", which is actually a great simplification of the World Health Organization's recommendations.
On the official website of the World Health Organization, the immunization procedures recommended for HPV vaccination are listed in detail, which are divided into the following situations: women aged 9-14 years are the highest priority group, vaccinated with one or two doses; young women aged 15-20 years can be given a single or two dose regimen; women over 21 years old should be given a two-dose regimen with an interval of 6 months; and people with low immunity such as HIV infection should be given three doses or at least two doses.
That is to say, except for women aged 9-20 who do not have immunocompromised problems, they can choose a one-dose vaccination regimen, and they still have to receive two or three doses.
Experts from the Guangdong Provincial Center for Disease Control and Prevention told the "Finance and Economics National Weekly" reporter that the World Health Organization put forward the proposal, behind which more considerations are that due to the impact of the new crown pneumonia epidemic and insufficient vaccine supply, the speed of HPV vaccination in many countries has declined, and single dose vaccination can effectively improve the vaccination rate of HPV vaccine, especially to increase the accessibility of low-income countries.
Guoxin Pharmaceutical Research Report believes that most of the research results of this SAGE review are based on persistent infection/immunogenicity in small age groups as a substitute endpoint, and the advance of the standard may lead to a decrease in the accuracy of the estimation of the final efficiency, while the peak of single dose vaccination and long-term antibody titers are lower than 2/3 doses of immunization procedures, and more data and longer-term continuous tracking of cervical cancer long-term protective efficacy are still needed.
In the mainland, the vaccination procedure for vaccines needs to perform a series of clinical studies, data support and market registration procedures. At present, several HPV vaccines that have been approved in China, the imported bivalent, quadrivalent and nine-valent vaccine immunization procedures are three doses, and the two domestic bivalent HPV vaccine immunization procedures are also three doses, but two doses can be used for women aged 9 to 14 years.
That is to say, at present, this discussion proposed by the World Health Organization will not change the mainland HPV vaccination program for the time being, and everyone still has to follow the vaccine instructions approved by the regulatory authorities.