Don't worry, the proposal has not landed yet
Written by | Yan Xiaoliu
Source | "Medical Community" public account
The topic of how many injections the HPV vaccine should be given is still fermenting.
Director of the Beijing Biological Products Research Association, Weibo "hot health and medical blogger" @ halogen vaccine On April 15, the article said: "There are many self-media advertising 1 shot = 2 shots / 3 shots ... Who really didn't say that. ”
How did the saying "just get 1 shot" come about?
The HPV vaccine is mainly used to prevent cervical cancer caused by human papillomavirus (HPV) infection. Some of the priced HPV vaccines have also been approved for the prevention of genital warts caused by HPV infection.
The "medical community" found that the information that caused the discussion of "HPV vaccine 1 shot top 3 shots" originated from the official website of the World Health Organization (WHO) on April 11.
On the same day, the WHO official website released "1 dose of HPV vaccine to provide solid protection against cervical cancer".
The ARTICLE outlines that on April 4-7 this year, the WHO's Advisory Expert Group on Immunization Strategies (SAGE) met to assess the evidence that has emerged over the past few years. It was noted that the 1-dose HPV vaccination regimen off-label can be effective in preventing cervical cancer caused by persistent HPV infection and is comparable to the 2-dose or 3-dose regimen.
According to WHO documents, persistent infection with high-risk HPV is a precancerous lesion and a trigger for cancer. Sage at the meeting recommended updating the HPV immunization program, including:
1 dose or 2 doses for girls aged 9-14 years who are the main targets of vaccination;
For women aged 15-20 years, 1 dose or 2 doses;
≥ 21-year-old women, given 2 doses at 6 months intervals between injections;
Immunocompromised people, including those living with HIV, should receive 3 doses if feasible and at least two doses if this is not feasible. There is limited evidence for the efficacy of a single dose in this population.
SAGE also noted that HPV vaccination should be carefully considered for boys and older groups until vaccine availability is not restricted.
Image from who
There are many limitations to promoting 1-dose vaccination
The "medical community" found slight differences between SAGE's latest recommendations and the WHO's current HPV immunization program.
According to the WHO's 2017 position paper, for women who are < 15 years of age at the time of first dose, a 2-dose vaccination regimen is recommended, with two doses spaced at 6 months and the maximum interval not exceeding 12-15 months. If the interval between the two doses is less than 5 months, the 3rd dose should be given at least 6 months after the first dose.
For women who are ≥ 15 years of age at the time of initial administration, and in immunocompromised and/or HIV-infected people (regardless of age), a 3-dose regimen is recommended at intervals of 0, 1-2, 6 months.
The so-called "position paper" is the WHO's guidance on health policy for member states to state its position on how to use vaccines globally.
The first version of the WHO position paper on hpvide vaccine, published in 2009, proposes that the target population should be given 3 doses over a 6-month period. Since then, the WHO has released updated versions in 2014 and 2017 respectively. < 15 years of age is recommended for 2 doses, first in 2014.
The "medical community" looked at the main points of the SAGE meeting and found that the "1 dose recommendation" was more based on public health considerations.
The primary reasons for the recommendations are the slow introduction of HPV vaccines into immunization programmes and the low overall population coverage. Especially under the covid-19 pandemic, related problems are prominent. According to UNICEF, the global shortage of HPV vaccines could continue into 2024.
According to SAGE data, global 2-dose HPV vaccination coverage decreased by 13% in 2020. This is related to school closures and limited supplies of vaccines.
At the same time, the status of HPV vaccination departs from the Global Strategy to Accelerate the Elimination of Cervical Cancer. The global strategy, launched in 2020, sets out targets such as full HPV vaccination for 90% of girls under the age of 15 globally by 2030. Based on the status quo, this goal is difficult to achieve.
The SAGE meeting concluded that the introduction of a 1-dose regimen for HPV vaccine should be accelerated, which is more efficient (less on average per cancer prevention), less costly and easier to implement than the 2-dose regimen.
The WHO press release quoted WHO Assistant Director-General Nothemba Simelela as saying that the 1-dose HPV vaccination proposal has the potential to drive the 2030 target faster.
Secondly, supported by clinical studies, 1 dose of HPV vaccination can provide a fairly high level of individual protection.
On the day of the press release, the New England Journal of Medicine (NEJM) published "The Efficacy of a Single Dose of HPV Vaccine in Young African Women." The article notes that within 18 months of the study, the 1 dose hpv vaccine was similar to the multi-dose regimen in preventing persistent infection.
It should be noted that "preventing persistent infection" and "whether or not to have cervical cancer" are not the same thing.
On the one hand, this has to do with the length of the study.
THE WHO documents state that cervical cancer can occur decades after HPV infection, with an average age of onset of 50 years. For women with a normal immune system, it takes 15-20 years from infection to development of cervical cancer.
Of the existing 1-dose vaccination studies, the earliest one with recognized results began in 2004 with the Costa Rica HPV Vaccine Trial. The participants were 7,500 women aged 18 to 25 years. To date, the subjects are under the age of 50. The NEJM study, on the other hand, only looked at data for 18 months after 1 dose.
"The observation time is not long enough" is almost a common problem faced by hpvic vaccine 1 dose efficacy studies. "Longer studies are needed to determine how long this protection can last." Ruanne Barnabas, one of the lead authors of the NEJM study and an associate professor of global health at the University of Washington School of Medicine and The School of Public Health, said.
Path for Appropriate Health Science and Technology (PATH) is one of the largest international non-profit organizations in the field of health worldwide. In 2020, the organization published a technical review of the available evidence for single dose HPV vaccination, saying that the duration of protection provided by a dose of HPV vaccine will be one of the determinants of whether a dose of hpvicide can be widely implemented. However, so far, although the relevant studies have shown the effectiveness of the 1-dose vaccine, they have not clearly given the duration of vaccine protection.
On the other hand, this is also related to research ethics. The WHO position paper states that the collection of cervical specimens from girls or adolescent women is neither realistic nor ethical. Therefore, most HPV vaccine studies have taken immunogenicity as the observation object, from which the clinical efficacy of the vaccine is inferred.
The Costa Rica HPV Vaccine Trial, for example, aims to compare whether antibody titers in different doses of vaccinators will change over time.
The UK only "got 1 shot"?
Whether SAGE's proposal will land is still unknown.
The WHO press release states that the full report of the SAGE meeting will be released on June 10 this year, and the report will prevail.
"The follow-up WHO will further consult on this and update the recommended plan." The press release said the WHO had not yet revised its position paper on HPV vaccination.
Even with the position paper revised, not all HPV vaccines apply to the "1 dose recommendation". According to SAGE meeting highlights, "This recommendation applies to HPV vaccines that have collected data for a single dose. "The subtext is that you can't do it without research data.
At present, some countries have moved.
In February, the UK Joint Commission on Vaccination and Immunization (JCVI) issued a "Provisional Recommendation for 1 Dose of HPV Vaccination".
"As early as 2018, JCVI realized that it might be necessary to implement 1 dose of vaccination. JCVI has been thinking about related issues in recent years and is now ready. The "Provisional Recommendation" states that for those < 14 years of age, the HPV vaccine immunization schedule will be changed from 2 doses to 1 dose. This recommendation is based on the results of the aforementioned Costa Rica HPV Vaccine Trial study and the IARC study in India, which began in 2009, and includes a number of studies on the effectiveness of 9-valent vaccines.
The "Temporary Recommendation" states that due to the COVID-19 pandemic, the priority for routine HPV immunization should be for all eligible children to receive at least the first dose. Thereafter, according to the actual situation in each place, consider providing or supplementing the second dose at an appropriate time.
"The above proposals are provisional and stakeholder consultations are being invited." JCVI said the deadline for response was 23:45 on March 24 this year.
As of this publication, the UK Health Security Agency (UKHSA) has not yet adopted the "Interim Recommendation" of the 1 dose regimen.
The ukhsa's most recent update on HPV vaccination guidelines took place on 1 April 2022. Its content shows that from now on, individuals who are ≥ 15 years old at the time of the first dose of vaccination, as well as people who have male sex, only need to receive 2 doses of HPV vaccine, which is considered "complete vaccination". This is 1 dose less than the previously required immunization schedule.
Eyes back to China. At present, the immunization procedures of HPV vaccine listed in mainland China are all 3 doses, which is based on the approved indications of Chinese clinical research data. Whether the dose will be adjusted in the future is not yet known.
Combining the above information, @Halogen Vaccine wrote an article proposing 3 personal views:
First, hpvic vaccines from any manufacturer should be given in accordance with the recommended procedures before more evidence of efficacy appears for precancerous lesions or cervical cancer.
Second, for those who fail to complete the follow-up HPV vaccination for various reasons, at least do not have to worry about safety or immunogenicity, and can complete the follow-up vaccination at a convenient time.
Third, based on the current situation of HPV vaccine supply in mainland China, under the condition of sufficient vaccine coverage and improved monitoring and screening level, the number of HPV vaccination doses per capita is reduced, and different age groups and gender vaccinations are opened.
Source:
1.SAGE April 2022 meeting highlights. WHO
2.One-dose Human Papillomavirus (HPV)vaccine offers solid protection against cervical cancer. WHO
3.JCVI interim advice on a one-dose schedule for the routine HPV immunisation programme. GOV.UK
4.Efficacy of Single-Dose Human Papillomavirus Vaccination among Young African Women. NEJM Evidence.doi.org/10.1056/EVIDoa2100056
5.Human papillomavirus vaccines: WHO position paper, May 2017. WHO
6. Vaccination 丨In the use of these five vaccines and vaccination recommendations, the WHO gave a new information. Brine said seedlings
7.Weekly Epidemiological Record. No.15,2009, pp. 118-131. WHO
8. Consensus of Chinese experts on the clinical application of human papillomavirus vaccine. Chinese Journal of Frontiers in Medicine. DOI:10.12037/YXQY.2021.02-01
9.HPV vaccination guidance for healthcare practitioners (version 6). GOV.UK
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