Cervarix

See also: HPV vaccines

Cervarix

Vaccine description
Target	human papillomavirus (Types 16 and 18)
Vaccine type	Protein subunit
Clinical data
Trade names	Cervarix
AHFS/Drugs.com	Monograph
MedlinePlus	a610014
Routes of administration	Intramuscular injection
ATC code	J07BM02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[1] CA: ℞-only / Schedule D[2] US: ℞-only[3][4] EU: Rx-only[5]
Identifiers
CAS Number	912337-47-4
ChemSpider	none
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Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).

Cervarix is designed to prevent infection from HPV types 16 and 18, that cause about 70% of cervical cancer cases.^[6] These types also cause most HPV-induced genital and head and neck cancers. Additionally, some cross-reactive protection against virus strains 45 and 31 were shown in clinical trials.^[7] Cervarix also contains AS04, a proprietary adjuvant that has been found to boost the immune system response for a longer period of time.^[8]

Cervarix is manufactured by GlaxoSmithKline. An alternative product, from Merck & Co., is known as Gardasil.^[6] Cervarix was voluntarily taken off of the market in the US in 2016 due to low demand.^[9]

Medical uses

HPV is a virus, usually transmitted sexually, which can cause cervical cancer in a small percentage of those women genital infected. Cervarix is a preventative HPV vaccine, not therapeutic. HPV immunity is type-specific, so a successful series of Cervarix shots will not block infection from cervical cancer-causing HPV types other than HPV types 16 and 18 and some related types, so experts continue to recommend routine cervical Pap smears even for women who have been vaccinated. Vaccination alone, without continued screening, would prevent fewer cervical cancers than regular screening alone.^[10][11]

Cervarix is indicated for the prevention of the following diseases caused by oncogenic HPV types 16 and 18: cervical cancer, cervical intraepithelial neoplasia (CIN) grade 2 or worse and adenocarcinoma in situ, and CIN grade 1. In the United States, Cervarix is approved for use in females 10 through 25 years of age^[12] while in some other countries the age limit is at least 45.^[13]

As of September 2009^[update], Cervarix was shown to be effective 7.3 years after vaccination.^[14]

Administration

Immunization with Cervarix consists of 3 doses of 0.5-mL each, by intramuscular injection according to the following schedule: 0, 1, and 6 months.^[6] The preferred site of administration is the deltoid region of the upper arm.^[6] Cervarix is available in 0.5-mL single-dose vials and prefilled TIP-LOK syringes.^[12]

Limitations of effectiveness

Cervarix does not provide protection against disease due to all HPV types, nor against disease if a woman has previously been exposed through sexual activity and protection may not be obtained by all recipients.^[12] It is therefore recommended that women continue to adhere to cervical cancer screening procedures.^{[citation needed]}

Adverse effects

• The most common local adverse reactions in ≥20% of patients were pain, redness, and swelling at the injection site.^{[citation needed]}
• The most common general adverse events in ≥20% of subjects were fatigue, headache, muscle pain (myalgia), gastrointestinal symptoms, and joint pain (arthralgia).^[12]

In common with some other prefilled syringe vaccination products, the tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber that may cause allergic reactions in latex sensitive individuals.^[15] The vial stopper does not contain latex.

Ingredients

The active components of the vaccine are:^[12][16]

• Human papillomavirus type 16 L1 protein 20 micrograms
• Human papillomavirus type 18 L1 protein 20 micrograms
• AS04 adjuvant, containing: 3-O-desacyl-4'- monophosphoryl lipid A (MPL) 50 micrograms adsorbed on aluminium hydroxide, hydrated (Al(OH)3) 0.5 milligrams Al 3+ in total

Biotechnology

Cervarix is created using the L1 protein of the viral capsid. L1 protein is in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology using a Baculovirus expression system which uses High Five Rix4446 cells derived from the insect Trichoplusia ni. The vaccine contains no live virus and no DNA, so it cannot infect the patient.^[12]

History

The research findings that pioneered the development of the vaccine began in 1991 by The University of Queensland investigators Jian Zhou and Ian Frazer in Australia . Researchers at UQ found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. Subsequently, the final form of the vaccine was developed in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute.^[17]

Clinical trials

Phase III trials have been conducted, including over 18,000 women from 14 countries in Asia-Pacific, Europe, Latin America and North America.^[18]

As of 2009, the manufacturer was conducting a trial to compare the immunogenicity and safety of Cervarix with Gardasil.^[19] Subsequent studies showed Cervarix generated higher antibody levels than Gardasil, the other commercially available HPV vaccine, upon testing seven months later, with twice the level for HPV type 16 and six times for HPV type 18.^[20]

Society and culture

Legal status

• Australia - Cervarix received approval in May 2007 in Australia for women ages 10 to 45.^[13]
• Philippines - On 25 August 2007, GlaxoSmithKline launched Cervarix in the Philippines after approval by the local Bureau of Food and Drugs.^[21]
• European Union - Cervarix was approved in September 2007 in the European Union.^[22]
• United States - The FDA approved Cervarix on 16 October 2009.^[23][24]
  • On 29 March 2007, GlaxoSmithKline submitted a Biologic License Application (BLA) for Cervarix (human papillomavirus vaccine, AS04 adjuvant-adsorbed), to the U.S. Food and Drug Administration (FDA) which included data from clinical trials in almost 30,000 females 10 to 55 years of age and contains data from the largest Phase III cervical cancer vaccine efficacy trial to that date.^[25]
  • GSK had awaited results of further trials to submit to the FDA. Approval had not been expected before late 2009.^[26]

In the United Kingdom it was included in the national vaccination programme for teenage and pre-teenage girls aged 12–13 and 17–18 from September 2008 to August 2012. This caused some controversy since Cervarix was chosen over Gardasil, even though Gardasil protects against additional HPV types 6 and 11 (which cause genital warts). However, the efficacy of Cervarix is higher.^[27]

References

1. "CERVARIX human papillomavirus vaccine types 16 and 18 [recombinant, AS04 adjuvanted] suspension for injection vial (126115)". department of Health and Aged Care.
2. "Archived copy" (PDF). Archived (PDF) from the original on 1 May 2022. Retrieved 10 October 2022.
3. "Cervarix". U.S. Food and Drug Administration (FDA). 4 October 2022. STN:BL 125259. Archived from the original on 10 October 2022. Retrieved 9 October 2022.
4. "Cervarix". U.S. Food and Drug Administration (FDA). 16 October 2009. Archived from the original on 22 July 2017. Retrieved 9 October 2022.
5. "Cervarix EPAR". European Medicines Agency (EMA). 23 December 2008. Archived from the original on 5 June 2022. Retrieved 9 October 2022.
6. Centers for Disease Control and Prevention (CDC) (May 2010). "FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP)". MMWR. Morbidity and Mortality Weekly Report. 59 (20): 626–629. PMID 20508593. Archived from the original on 3 August 2017. Retrieved 9 September 2017.
7. "New data show Cervarix, GSK'S HPV 16/18 cervical cancer candidate vaccine, is highly immunogenic and well-tolerated in women over 25 years of age". GlaxoSmithKline. 5 June 2006. Archived from the original on 27 September 2007. Retrieved 27 January 2007.
8. "Cervical Cancer Vaccines: Cervarix". Emory University. 21 August 2006. Archived from the original on 9 October 2006. Retrieved 27 January 2007.
9. "GSK exits U.S. market with its HPV vaccine Cervarix". FiercePharma. 21 October 2016. Archived from the original on 9 July 2021. Retrieved 6 July 2021.
10. Harper, D. (2009). "Current prophylactic HPV vaccines and gynecologic premalignancies". Current Opinion in Obstetrics and Gynecology. 21 (6): 457–464. doi:10.1097/GCO.0b013e328332c910. PMID 19923989. S2CID 24765340.
11. Marcia G. Yerman (28 December 2010). "An Interview with Dr. Diane M. Harper, HPV Expert". The Huffington Post. Archived from the original on 27 July 2018. Retrieved 12 January 2010.
12. "Cervarix Prescribing Information" (PDF). Food and Drug Administration. Archived (PDF) from the original on 23 November 2010. Retrieved 3 August 2010.
13. Glaxo cervical cancer shot approved in Australia Archived 4 May 2021 at the Wayback Machine Reuters (21 May 2007) Retrieved on 25 May 2007
14. Schwarz, T. F. (2009). "Clinical update of the AS04-Adjuvanted human Papillomavirus-16/18 cervical cancer vaccine, cervarix®". Advances in Therapy. 26 (11): 983–998. doi:10.1007/s12325-009-0079-5. PMID 20024678. S2CID 44625098.
15. "Latex in Vaccine Packaging" (PDF). Centers for Disease Control and Prevention (CDC). May 2010. Archived (PDF) from the original on 13 April 2010. Retrieved 11 August 2010.
16. http://emc.medicines.org.uk/medicine/20207/PIL/Cervarix/ Archived 7 March 2010 at the Wayback Machine Patient Information Leaflet
17. McNeil, C. (2006). "Who invented the VLP cervical cancer vaccines?". J Natl Cancer Inst. 98 (7): 433. doi:10.1093/jnci/djj144. PMID 16595773.
18. Paavonen J, Naud P, Salmerón J, et al. (July 2009). "Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women". Lancet. 374 (9686): 301–14. doi:10.1016/S0140-6736(09)61248-4. PMID 19586656. S2CID 1331989.
19. Einstein MH, Baron M, Levin MJ, et al. (October 2009). "Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years" (PDF). Hum Vaccin. 5 (10): 705–19. doi:10.4161/hv.5.10.9518. PMID 19684472. S2CID 23610327. Archived (PDF) from the original on 1 August 2014. Retrieved 28 November 2010.
20. "CERVARIX". RxList. Archived from the original on 10 July 2021. Retrieved 10 July 2021.
21. "Vaccine vs cervical cancer virus launched in Manila". GMA Network. Associated Press. 25 August 2007. Archived from the original on 27 August 2007. Retrieved 25 August 2007.
22. "Glaxo prepares to launch Cervarix after EU okay". Reuters. 24 September 2007. Archived from the original on 25 October 2008. Retrieved 18 July 2008.
23. "FDA approves Cervarix, GlaxoSmithKline's cervical cancer vaccine" (Press release). GlaxoSmithKline. 16 October 2009. Archived from the original on 19 October 2009. Retrieved 30 October 2009.
24. "October 16, 2009 Approval Letter - Cervarix". U.S. Food and Drug Administration (FDA). 16 October 2009. Archived from the original on 19 October 2009. Retrieved 13 November 2009.
25. "Cervarix - Glaxo HPV Vaccine Filed With FDA". Vaccine Rx. 29 March 2007. Archived from the original on 28 September 2007. Retrieved 30 March 2007.
26. "GSK Does Not Expect FDA Approval Of HPV Vaccine Cervarix Until End Of 2009". Archived from the original on 29 August 2008. Retrieved 18 July 2008.
27. Hawkes, Nigel (18 July 2008). "Anger over Department of Health choice of cheaper cancer vaccine". The Times. London. Archived from the original on 18 September 2011. Retrieved 18 July 2008.

Further reading

• Ireland, Corydon (2006). "A Cancer Vaccine is Born". Rochester Review. 68 (3). University of Rochester.

External links

• "Human Papillomavirus (HPV) Vaccines". National Cancer Institute. 18 June 2021.
• McNeil, Donald G. Jr. (29 August 2006). "How a Vaccine Search Ended in Triumph". The New York Times.