The three statistical models (power-law, modified power-law and piece-wise models) provide a robust and reproducible way of predicting long-term persistence of antibodies against HPV 16 and 18. All three models show that the levels of antibodies against HPV 16 and 18 induced by CervarixTM will remain significantly above those seen following natural infection for over 20 years.2
"Predicting the levels of antibodies generated and sustained against HPV 16/18 is important as long as we have no better options to directly measure duration of protection," said Dr. Koen Van Herck of the Centre for the Evaluation of Vaccination, Antwerp, Belgium. "Long-term immune response is particularly important when vaccinating adolescents and young women against cervical cancer as new infections with cancer-causing HPV types can occur throughout their lives."
The statistical models used in this study utilised data from an ongoing phase II study conducted up to 6.4 years. This is the longest study in HPV vaccination to date and will continue to provide data on antibody levels against both HPV 16 and 18 for up to 9.5 years.3
Data from this study show that CervarixTM has demonstrated high and sustained antibody levels associated with 100 percent efficacy in preventing pre-cancerous lesions caused by HPV 16/18 for up to 6.4 years.3 The study also showed that CervarixTM induces antibody levels that remain significantly higher than the body's own immune response to natural infection from cancer-causing virus types 16 and 18 for up to 6.4 years.3
CervarixTM is formulated with the innovative adjuvant system AS04, specifically designed and selected to enhance the immune response against HPV, which is responsible for cervical cancer. Data show that CervarixTM, induces a stronger and more sustained immune response compared to the same vaccine antigens formulated with conventional aluminium hydroxide alone.4
Favourable tolerability profile for CervarixTM
Additional data from an integrated analysis of 11 phase II and III trials involving nearly 30,000 adolescent girls and women aged 10-72 years presented at EUROGIN, confirmed the favourable tolerability profile of CervarixTM.5 The most common solicited local symptoms associated with CervarixTM vaccination are comparable with those experienced following administration of common vaccines generally given to adolescents, i.e. BoostrixTM-polio vaccine.5 The study showed that the solicited local symptoms were transient and mild and did not adversely affect compliance.5
Previous data sets from the same integrated analysis have shown that no differences were observed between the CervarixTM and control groups in serious adverse events and medically significant conditions after the completion of the three-dose vaccination schedule.6 This is the largest safety analysis of cervical cancer vaccination reported to date and included a geographically and ethnically diverse population with a very broad age range.
Cervarix TM and Boostrix TM are trade marks of the GlaxoSmithKline group of companies.
About data modelling
The modelling analyses utilised in the trial are based on three independent statistical formulae and have been widely used to predict the duration of effect expected of new medicines, including vaccines. The modelling analyses tracked the levels of HPV 16 and 18 (the most common cancer-causing HPV types1) over time using real-life patient data gathered during an ongoing phase II clinical trial for CervarixTM over a period of up to 6.4 years - the longest ever cervical cancer vaccination study to date.3
Following the initial peak of antibody levels at six months, the levels of antibodies against HPV 16 and 18 stabilise gradually over time to plateau at a constant level significantly above that seen following natural infection.2
Antibodies and vaccination
Vaccines help the body to develop immunity before exposure to a particular pathogen, such as a bacterium, virus, or toxin. The immune system identifies such 'foreign' substances, which are known as antigens, and develops specific proteins against them - these are antibodies.
In addition to the importance of high and sustained antibody levels over time, the quality and location of these antibodies is equally important.7 For HPV, which is a local, mucosal virus that evades the immune system,8,9,10 the antibodies that are important are those responsible for blocking the initial cervical infection.7 These are called neutralising antibodies, because they have the ability to neutralise the cancer-causing virus types by preventing them from infecting cells in the cervix. The role of these neutralising antibodies is supported by the World Health Organization, which states that neutralising antibodies are the likely mediator of protection.11
CervarixTM was specifically formulated with a novel adjuvant, AS04, to deliver high and sustained levels of antibodies aimed at providing long-term protection against the most common and aggressive cancer-causing HPV types, HPV 16 and 18.1
CervarixTM has been shown to induce antibodies that reach the cervix,12 the site of infection, where they would be able to block the virus from entering the cells.7
CervarixTM has been shown to be well tolerated in clinical trials involving over 58,000 women. The most common side effect seen was pain at the site of injection, which often occurs when a vaccine is administered, and is not long lasting.
CervarixTM is also the only cervical cancer vaccine that has been shown to provide high levels of cross-protection against persistent infection caused by HPV 45,13, 14 one of the most common cancer-causing HPV types after HPV 16 and 18.1 HPV 45 is responsible for a significant proportion of cases of adenocarcinoma,13 a very aggressive type of cancer more common in younger women.13
To date, CervarixTM has been approved in more than 80 countries around the world, including the 27 member states of the European Union (EU), Australia, Brazil, Korea, Mexico and Taiwan. CervarixTM is not approved in the USA.
Confidence in CervarixTM has been demonstrated by the fact that, since its approval in 2007, the GSK vaccine has won approximately two thirds of tenders in Europe where both GSK and the competitor vaccine have applied.
About HPV and cervical cancer
Approximately 100 types of human papillomavirus have been identified to date15 and, of these, approximately 15 virus types are known to cause cervical cancer.15 HPV types 16 and 18 are responsible for approximately 70 percent of cervical cancers globally with 45 and 31 accounting for another 7 percent.1 Persistent infection with cancer-causing HPV types can lead to abnormal Pap smears, cervical pre-cancer and cervical cancer. Worldwide, more than 500,000 women will be newly diagnosed with cervical cancer and 280,000 women will die from it each year.16
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and health care companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit http://www.gsk.com.
About GlaxoSmithKline Biologicals
GlaxoSmithKline Biologicals (GSK Biologicals) is a global vaccine company which has shown itself to be a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 14 manufacturing sites strategically positioned around the globe. In 2007 GSK Biologicals distributed 1.1 billion doses of vaccines to 169 countries in both developed and the developing world - an average of 3 million doses a day.
GSK Biologicals employs over 9,000 people worldwide including more than 1,600 passionate scientists engaged in research aimed at discovering innovative vaccines that contribute to the health and well-being of people of all generations around the world.
1. Bosch FX, Burchell AN, Schiffman M et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine 2008; 26S: K1-K16
2. David M-P, Hardt K, Tibaldi F et al. Modelling of long-term persistence of anti-hpv-16 and anti-hpv-18 antibodies induced by an as04-adjuvanted cervical cancer vaccine. Abstract at European Research Organisation on Genital Infection and Neoplasia (EUROGIN), Nice, France, November 12-15 2008
3. Wheeler C, Teixeira J, Romanowski B et al. High and sustained HPV 16 and 18 antibody levels through 6.4 years in women vaccinated with CervarixTM (GSK HPV-16/18 ASO4 vaccine) Abstract at European Society for Paediatric Infectious Diseases (ESPID), Graz, Austria, 14-16 May 2008
4. Giannini SL, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminum salt combination (AS04) compared to aluminium salt only. Vaccine 2006 24: 5937 - 5949
5. Rombo L, Schwarz TF, Thomas F et al. Tolerability of hpv-16/18 as04-adjuvanted cervical cancer vaccine. Abstract at European Research Organisation on Genital Infection and Neoplasia (EUROGIN), Nice, France, November 12-15 2008
6. Descamps D, Hardt K, Spiessens B et al. Safety of human papillomavirus (Hpv)-16/18 AS04 adjuvanted vaccine for cervical cancer prevention: integrated summary of 11 clinical trials. Abstract at ESPID's Annual Meeting, May 13-16, 2008, Graz, Austria.
7. Villa L. Vaccines against papillomavirus infections and disease. Rev Chil Infectologia. 2006; 23(2): 157-159
8. Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006; 24S3:S1-S10.
9. Stanley M. Immune responses to human papillomavirus. Vaccine. 2006; 24 Suppl 1:S16-22.
10. Tindle RW. Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer. 2002;2:59-65.
11. World Health Organization WHO_meeting on the standardization of HPV assays. January 2008. Retrieved from http://www.who.int/
12. Poncelet S, Cambron S, Giannini SL et al. Induction of Cervical Mucosal HPV IgG in Women 15-55 Years Old Following Systemic Vaccination with GSK's prophylactic Cervical Cancer Candidate Vaccine. Presented at the International Papillomavirus Conference (IPC), Beijing, China, 3-9 November, 2007
13. Jenkins, D. Cross-protection against oncogenic non-vaccine HPV types by Cervarix™, an HPV-16/18 AS04-adjuvanted cervical cancer vaccine, in previously unexposed women. Gynaecologic Oncology. 110 (2008) S18 - S25
14. Harper D, Gall S, Naud P et al. HPV-007 Efficacy Abstract. "Sustained Immunogenicity and high efficacy against HPV-16/18 related cervical neoplasia: Long-term follow-up Through 6.4 Years in Women Vaccinated with CervarixTM (GSKs HPV 16/18 AS04 Candidate Vaccine). Abstract at The Society of Gynecologic Oncologists Annual Meeting (SGO), Tampa, Florida, 9-12 March, 2008
15. Muñoz N, Bosch FX, Castellsague X. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 111; 278-285 (2004)
16. WHO. Initiative for Vaccine Research accessed on October 1, 2008 at http://www.who.int/vaccine_research/diseases/hpv/en/