HPV vaccine is to protect girls? Wrong, men and women are equal in front of HPV!

HPV virus can distinguish between men and women?

According to the data of the International Agency for Research on Cancer in 2019, it is estimated that nearly 570000 women will suffer from cervical cancer worldwide in 2018, and more than 310000 women will die of cervical cancer. There are nearly 110000 new cases and 50000 deaths of cervical cancer in China.

The only cancer caused by virus

Research shows that cervical cancer is the only cancer caused by a virus, which is called human papillomavirus (HPV). HPV can be divided into high-risk type and low-risk type according to carcinogenicity. IARC classified the following 12 groups as high-risk groups according to epidemiological data: HPV 16, HPV 18, HPV 31, HPV 33, HPV35, HPV 39, HPV 45, HPV 51, HPV 52, HPV 56, HPV 58 and HPV 59. High risk HPV can be detected in 99.7% of cervical cancer, and HPV 16 and HPV 18 are the most common.

Four high risk HPV viruses

HPV not only affects women, but more than 4 out of every 10 cancers caused by HPV occur in men.

In the United States, more than 14000 men suffer from cancer due to HPV every year. High risk HPV can cause cancers in the anus, penis, head and neck, while low risk HPV can cause diseases such as anal genital warts and recurrent respiratory papilloma,

At present, HPV infection can be prevented by vaccination.

At present, there are three kinds of HPV vaccines on the market, namely 2-valent HPV vaccine, 4-valent HPV vaccine and 9-valent HPV vaccine

Technical route for research and development of HPV vaccine

At present, the main expression platforms include E. coli, yeast and baculovirus/insect cell.

1. GlaxoSmithKline uses baculovirus (BV) to transfect insect cells to produce L1 VLP. Recombinant BV has certain immunogenicity and can induce innate immune response. Therefore, it needs to fully remove impurities such as recombinant BV and cell DNA, and the production system is relatively complex.

2. MSD uses a stable L1 recombinant Saccharomyces cerevisiae production system. Saccharomyces cerevisiae uses glucose/galactose as the carbon source, which is safe and will not produce endotoxin. The process is relatively simple, the fermentation cycle is short, and the protein expression has certain post-translational processing and glycosylation modification, but there is a certain difference from the glycosylation in animal cells (hyperglycosylation).

3. Vantai Biological Escherichia coli prokaryotic expression vaccine antigen technology, combined with a new adjuvant system, develops a new generation of HPV vaccine. With strong reproduction ability of E. coli, high protein expression level, simple downstream process and easy control, the cost control is more efficient compared with yeast, baculovirus/insect cells and other eukaryotic expression systems.

One dose of HPV vaccine is hard to get

According to statistics, taking bivalent HPV vaccine as an example, assuming that women aged 9 to 15 have two injections per person, 68 million will be needed based on 70% vaccination rate; For women aged 16 to 26 and 26 to 45, the vaccination rate is 40% and 20% respectively. Three injections per person. The estimated demand is 200 million. At present, the production capacity of HPV vaccine cannot meet the demand. Even domestic bivalent HPV vaccine is still in a stage of short supply.

The United States: The vaccination rate is steadily rising, and there is still much room for improvement.

In 2007, HPV vaccine was officially included in the NIP of the United States. In 2010, the recommended population was expanded from women aged 11-12 to all adolescents aged 11-12. The United States government has also been committed to re vaccinating HPV vaccine for adults aged 18-26. In 2017, NIP in the United States changed the recommended vaccination procedure for 9-14 year olds to 2 doses.

Australia and Britain: The advantages of campus vaccination are obvious, and the coverage of vaccines is effective. HPV vaccines in Australia and the United Kingdom are mainly based on campus vaccination, and both have re vaccinated the school-age population. At present, the coverage rate of HPV vaccine for the age group in both countries has reached about 80%.

Canada: Female vaccination rate is high, and male vaccination has been carried out successively. In February 2007 and January 2012, the Canadian National Advisory Committee on Immunization listed the 4-valent HPV vaccine as the recommended vaccine for women aged 9 to 26 years and men aged 10 to 26 years. In September 2007, Canada's administrative regions launched the campus vaccination program for female HPV vaccine (grades 4-8); From 2013 to 2016, some administrative regions successively expanded the HPV vaccination program on campus to boys in grades 6-9.

China: The female vaccination rate is high. The estimated 9-valent HPV vaccination rate is higher in economically developed and highly educated regions, and the proportion of vaccination times in all HPV vaccination times is also high. It is reported that older women in China have been vaccinated with HPV vaccine before teenagers.

Main controversial points of HPV vaccine

Clinical endpoint

? WHO regards persistent infection as the clinical endpoint to measure the effectiveness of HPV vaccine, but only a small proportion of persistent infection will lead to cervical cancer. The clinical endpoint has some limitations. The effectiveness of HPV vaccine in preventing cervical cancer still needs further research.

? The carcinogenesis induced by HPV infection requires the joint action of other risk factors, and the impact of other risk factors on the effectiveness of HPV vaccine cannot be measured only by taking persistent infection as the clinical endpoint.

? 16/18 HPV is only related to 70% of cervical cancer, and clinical trials often measure the protection rate of cervical cancer by the prevention effectiveness of 16/18 HPV infection, which is one-sided.

Protection period: The immune protection period of HPV vaccine is not yet determined. The long-term follow-up study is still in progress, and whether further immunization is needed remains to be determined.

Therapeutic: HPV vaccine is only preventive but not therapeutic, so it can only effectively prevent uninfected HPV subtypes, but has no obvious effect on previously infected HPV subtypes. Therapeutic HPV vaccine is the main direction of subsequent research and development.

Artificial selection of strains: The large-scale use of HPV vaccine may change the distribution proportion of HPV subtypes in nature. After the coverage subtypes are contained, a non coverage high-risk subtype may develop into a new dominant strain.

Some references:

1. WHO-HPV: https://www.cdc.gov/hpv/index.html

2. Estimated coverage rate of human papillomavirus vaccine for women aged 9 to 45 years in China from 2018 to 2020. DOI: 10． 19914 /j． CJVI． 2021101

3. Guangzhou Hengsheng - cytological examination+AI and HPV examination is the future development trend

4. Northeast Securities - HPV Vaccine: China's market volume from a global perspective

5. Guosen Securities -- the rise of domestic HPV vaccine, the golden decade of stock market

6. Cao Wangli et al., Research and development status and development trend of therapeutic vaccines at home and abroad

7. Margaret Stanley --Pathology and epidemiology of HPV infection in females