After the nine-valent HPV vaccination age window is relaxed, these 3 issues need attention

When will boys be included?

Writing |Yan Xiaoliu

Source | “Medical Community” Public Account

In the past two days, two pieces of human papillomavirus (HPV) related news have been hotly debated.

First, an 18-year-old woman went to the doctor with “cauliflower” growing in her lower body. It was found that he was infected with 10 HPV subtypes, 7 of which were high-risk types.

Cheng Hao, director of the Department of Dermatology at Run Run Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, received the patient, saying that it is not uncommon to be infected with high-risk HPV at a young age. He is not only concerned about the physical and mental health of patients, but also laments that prevention work has a long way to go.

The early vaccination of the HPV vaccine is an important means of preventing infection.

At the same time as the aforementioned news dissemination, Merck (China) officials announced that the applicable population of its nine-valent HPV vaccine has been expanded from the original 16-26-year-old women to 9-45-year-old women.

So far, 5 HPV vaccines have been approved for marketing in my country, 4 of which are suitable for women aged 9-45. In addition to the above-mentioned nine-valent vaccines, the other three are bivalent vaccines.

Vaccination age window widened, but “later shots” not recommended

After this age expansion, the applicable age of the nine-valent HPV vaccine in China will be the same as that in the United States.

In 2018, the United States completed the age expansion of the applicable population. At that time, U.S. regulators quoted data saying that about 3,200 women aged 27-45 were followed up for 3.5 years and found that the nine-valent vaccine was 88% effective in preventing precancerous lesions and cervical cancer in this age group.

Information on the official website of the Mayo Clinic in the United States states that even if adults have been infected with HPV, vaccination is still beneficial. “It protects you from other virus subtypes.”

However, combined with the statement of the British and American CDCs, the applicable age does not equal the recommended age.

The CDC says some 27-45-year-olds can discuss the benefits of vaccination with a clinician, but it is “not recommended for those over 26,” for “several reasons. Including most people in this age group who have been exposed to HPV, the benefit of vaccination is very low.”

In November 2021, The Lancet published an article stating that based on data on girls in three age cohorts in the UK, 12-13, 14-16, and 16-18, it is possible to obtain Provide various information. Including, regardless of HPV status at enrollment, there was a significant reduction in the incidence of cervical precancer in vaccinated individuals. And, the earlier the vaccination, the higher the protective efficacy.

In the same year, Harvard T.H. Chan School of Public Health issued a document stating that taking into account age and sexual activity level, etc., the health benefits of vaccination for people over 26 years old are low and the cost is high. “Cervical cancer screening is an effective and affordable option for this age group.”

Currently, the World Health Organization (WHO) recommends that the optimal age for vaccination is 9-14 years old.

Start at age 9, or just two shots

In countries such as the United Kingdom and the United States, the HPV vaccine has been included in the “routine vaccination list” for 12-13 year olds or 11-12 year olds. Boys and girls have to fight.

The CDC states that people under the age of 15 when the first dose is vaccinated only need two doses separated by 6-12 months. Those who started the vaccine after the age of 15 and those who are immunocompromised need 3 doses.

According to WHO, the “reduced dose” is because 9-14-year-olds have strong immune memory and have not had sex, and the antibody titers produced by vaccination are higher. At the same time, when the follow-up vaccine is sufficient, there are also opportunities for replanting.

In April, the WHO convened a Strategic Expert Group on Immunization (SAGE) meeting, which also reviewed evidence that people aged 9-15 receive only one dose of the vaccine. The panel believes that this produces the same immune effect as 2-3 doses.

“HPV infection can be spread through any skin-to-skin contact, with symptoms appearing on areas such as the fingers, mouth, and genitals. This means the virus can be spread in many ways, including touch. Before exposure to the virus – In other words, before they become sexually active – vaccination works best,” the NHS noted.

The benefits of ‘early vaccination’ in the UK are already evident. The aforementioned Lancet article noted that the country launched its HPV vaccination program in 2008. Cervical cancer has been almost eliminated in women born after September 1, 1995 through vaccination.

The official website of the State Council Working Committee on Women and Children issued a document at the end of 2021, supporting “the sooner the better.” The article pointed out that the first peak age of Chinese women infected with high-risk HPV is 15-24 years old. The HPV vaccine is most effective when vaccinated before this age.

However, the actual coverage of HPV vaccine in my country is low, not to mention the adolescent population. According to the data of the Shanghai Municipal Immunization Program, as of the end of 2019, the population of females aged 9-45 in Shanghai was estimated to be 5.971 million, and the whole vaccination rate was only 2.83%.

Correspondingly, in 2016, 79% of girls and 73% of boys in Australia were vaccinated by the age of 15.

In July of this year, the National Health and Medical Commission publicly stated that it would encourage local governments to take the lead in the first trial, focusing on promoting the introduction of free HPV vaccination policies in areas with mature conditions, and continuously increasing the HPV vaccination rate of school-age girls.

As of March 2021, the first batch of 15 pilot cities in my country has been released. They are the forerunners in promoting the public-funded HPV vaccination strategy, aiming to achieve the WHO’s “90-70-90” target by 2025. One of the “90s” is that 90% of women are vaccinated by the age of 15.

Men vaccinated, pending

In response to the expansion of the age of the nine-valent vaccine, the common concerns of the public include: Do you want to use the nine-valent vaccine if you have already received the bivalent or quadrivalent vaccine?

The higher the number, the higher the number of HPV subtypes that can be prevented. However, the mainstream view of health departments and CDCs in various countries is that early vaccination is more important than the price. Even the bivalent vaccine already prevents most infections.

The aforementioned “Lancet” articles were included in the observation subjects, and all were vaccinated with bivalent vaccine. Results showed that this reduced cervical cancer by 87% and cervical intraepithelial neoplasia grade 3 (CIN3) by 97%.

In 2020, the New England Journal of Medicine published an 11-year follow-up study in Sweden, and almost all women interviewed were vaccinated with the quadrivalent HPV vaccine. After adjusting for factors such as age and medical history, it was found that the risk of cervical cancer was significantly reduced by 63% for the vaccinated. Among those who completed the vaccination before age 17, the associated risk was reduced by 88%.

The US CDC document states that if only one dose of bivalent or quadrivalent vaccine has been administered, subsequent vaccinations can be completed with the nine-valent vaccine. For those who have completed the full course of bivalent or quadrivalent vaccine, an additional nine-valent vaccine is not recommended. The benefit of this approach is too small, and there is insufficient clinical data to support it.

“When will boys be vaccinated against HPV” is also one of the topics of public concern. Previously, the HPV vaccine has been included in the vaccination of men aged 9-45 by the US FDA. However, the aforementioned Harvard T.H. Chan School of Public Health study said there is still a lack of data on the protective efficacy of men over the age of 26.

In 2021, China will launch a large Phase 3 clinical trial to evaluate the protective efficacy, immunogenicity and safety of the nine-valent HPV vaccine in men.

Shao Yinan, the author of “Man Talking Vaccines”, pointed out that after the nine-valent age expansion, more people of the right age will realize the importance of vaccines and increase the demand for vaccines. It may be more difficult to open up male vaccinations until vaccine supplies are sufficient.

SAGE urges all countries to prioritise missed vaccinations for multiple age groups and catch-up of older girls so that more girls and women can be vaccinated, according to the WHO website. SAGE also noted that HPV vaccination of boys and older groups should be carefully considered until vaccine availability is not limited.


[1]Sad! An 18-year-old girl in Zhejiang went to the doctor after 2 months of “cauliflower”. The doctor was shocked: she was infected with 10 HPV subtypes at the same time, which is very rare. Beijing Youth Daily

[2]HPV Vaccination Recommendations.CDC

[3]Human papillomavirus vaccination for adults aged 30 to 45 years in the United States:A cost-effectiveness analysis.PLOS


[4]HPV Vaccination and the Risk of Invasive Cervical Cancer.N Engl J Med.2020;383:1340-1348.DOI:10.1056/NEJMoa1917338

[5] Popularize HPV vaccination and let women say goodbye to cervical cancer completely. State Council Working Committee on Women and Children

[6]Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV.CDC

Source: Medicine

Editor in charge: Tian Dongliang

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