Vaccination is the most effective way to prevent potential HPV infections. The prophylactic HPV vaccine is mainly designed to prevent specific types of HPV infections by eliminating the virus’ nucleic acids, retaining its nucleocapsid protein L1, and enabling the formation of virus-like particles (VLPs), which can express viral antigens after intramuscular injection, stimulate humoral immunity, and produce neutralizing antibodies that bind to the viral antigens as soon as the HPV enters the organism.
This prevents specific types of HPV infection and the development of cervical intraepithelial neoplasia. To date, various prophylactic HPV vaccines targeting different HPV genotypes are available on the market, including bivalent, quadrivalent, and nine-valent (nonavalent) vaccines. Table 1 describes the details of the vaccines approved for marketing in China. These vaccines are for prophylactic use only and do not clear pre-existing HPV infections or treat HPV-related diseases.
Table 1. Human Papillomavirus (HPV) Vaccine approved for marketing in China
| Product name | Gardasil 4 | Cervarixc | Gardasil 9 | Cecolin | Walrinvax |
| Type | Quadrivalent | Bivalent | Nine-valent | Bivalent | Bivalent |
| Manufacturer | Merck | GlaxoSmithKline | Merck | Innovax | Walvax |
| Global Launch Time | 2006 | 2009 | 2014 | 2019 | 2022 |
| China Launch Time | 2017 | 2016 | 2018 | 2019 | 2022 |
| Transgenic Vector | Brewer’s yeast | Infection of insect cells by baculoviruses | Brewer’s yeast | Escherichia coli (E. coli) | Picros yeast |
| HPV virus type | |||||
| High-risk HPV | 16/18 | 16/18 | 16/18/31/33/45/52/58 | 16/18 | 16/18 |
| low-risk HPV | 6/11 | – | 6/11 | – | – |
| Age Eligibility | Women aged 9-45 | Women aged 9-45 | Women aged 9-45 | Women aged 9-45 | Women aged 9-30 |
| Vaccination Doses | 3 doses | 3 doses 2 doses for 9-14 | 3 doses 2 doses for 9-14 | 3 doses 2 doses for 9-14 | 3 doses 2 doses for 9-14 |
| Vaccination interval | 0, 2 month, 6 month | Day 1, 1 month later, 6 months later | Day 1, 2 months later, 6 months later | Day 1, 1 month later, 6 months later | Day 1, 2 months later, 6 months later |
| Vaccination interval (2 dose) | Day 1, 6 months later | Day 1, 6-12 months | Day 1, 6 months later | Day 1, 6 months later | |
Bivalent vaccine
The bivalent vaccine targets HPV 16/18 and prevents about 70% of cervical cancers associated with these two HPV types. Globally, the first bivalent HPV vaccine was licensed in 2007 and has been approved for the prevention of cervical pre-cancerous lesions and cervical cancer in females aged 9 years and older; the manufacturer of the vaccine has not yet declared an indication for use in males. China currently has three bivalent vaccines approved for marketing: Cervarixc, produced by GlaxoSmithKline; Cecolin, produced by Xiamen Innovax; and Walrinvax, produced by Walvax. The bivalent vaccines usually apply a 3-dose schedule of 0, 1, and 6 months. For ages 9-14 years, all three approved bivalent vaccines can be administered using a 2-dose schedule of 0 and 6 months.
Quadrivalent vaccine
The quadrivalent vaccine contains virus-like particles of HPV6, HPV11, HPV16, and HPV18, targeting about 70% of cervical cancers associated with HPV16/18 and 90% of genital warts caused by low-risk HPV6/11. Globally, the quadrivalent vaccine was first licensed in 2006 by the FDA for the prevention of precancerous or dysplastic lesions, cervical cancer, and genital warts (condyloma acuminatum) among females 9 through 26. The quadrivalent vaccine is also later approved for the prevention of precancerous lesions of the vulva and vagina, and vulva and vaginal cancer. In some countries, the vaccine is approved for the prevention of genital warts in men. In China, the Merck vaccine was approved in May 2017 for use in females aged 9-45 years. The quadrivalent vaccine is administered at 0, 2, and 6 months for a 3-dose schedule.
Nine-valent vaccine
The nine-valent (nonavalent) vaccine adds five new HPV types to the quadrivalent vaccine, including HPV31/33/45/52/58, which protects against cancers of the cervix, vulva, anus, and vagina, as well as genital warts and other diseases. With the added types, the effectiveness of 9-valent vaccine’s protection against cervical cancer increases to 90%. The nine-valent vaccine was approved for marketing in December 2014 by the United States. In China, the Merck nine-valent vaccine, named Gardasil®9, was approved by the National Medical Product Administration (NMPA) for conditional marketing in April 2018 for use in females aged 16-26. In August 2022, a new indication was approved by the NMPA, expanding the approved use of the vaccine to include females aged 9-45 years. The nine-valent vaccine is administered using a 3-dose schedule of 0, 2, and 6 months. In January 2024, NMPA approved a 2-dose vaccine schedule (0, 6-12 months) for Gardasil®9 in girls aged between 9 to 14 years.
Content Reviewer: Kelly Hunter, Zhangyang Pan
Page Editor: Jiaqi Zu
