GSK's Cervical Cancer Vaccine Induces Antibodies To Target Cervical Cancer Where It Starts

Main Category: Cervical Cancer / HPV Vaccine
Article Date: 06 Nov 2007 - 1:00 PDT

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Two years after the first of three doses, antibodies against the two most common cervical cancer-causing virus types, induced by a vaccine, have been found where they are needed, in the cervix, according to new data presented at the International Papillomavirus Conference (IPC) in Beijing.1

GlaxoSmithKline's (GSK) cervical cancer vaccine CervarixTM has been shown to induce antibodies against the two most common cancer-causing virus types, 16 and 18, which were detectable in the cervix, where the virus infects and replicates. High correlation between the levels of antibodies in the bloodstream and in the cervix were observed up to two years after the first of three doses of the vaccine, in women 15-55 years of age.1

"The human papillomavirus types that cause cervical cancer are particularly challenging - the virus can evade the immune system by replicating only in the cervix. This study shows that the vaccine is able to induce antibodies in the blood that can reach the cervix, where the virus infects and develops into cervical cancer and where protection is mostly needed" comments Professor Tino Schwarz, Head of the Central Laboratory at the Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg, Germany.

"The high correlation between antibodies induced by CervarixTM in the bloodstream and those able to reach the cervix provides further insights on the quality of the immune response induced by the vaccine, and also on how the vaccine may help provide protection against cancer-causing virus types," explains Dr Hugues Bogaerts, MD ,Vice President of Worldwide Medical Affairs HPV at GSK Biologicals.

"We expect this correlation to remain high in time, as we know the observation of cervical antibodies was made at 24 months, which is the time when levels of vaccine-induced antibodies in the bloodstream become stable and are maintained for at least five years, according to data from existing trials on our cervical cancer vaccine" concludes Dr Bogaerts.

CervarixTM is formulated with a novel adjuvant technology, the adjuvant system AS04, specifically designed and selected to enhance the immune response against the human papillomavirus responsible for cervical cancer.

Antibodies where it matters, at any age

These data on antibody levels in the cervix are part of an ongoing study investigating the immune response induced by GSK's cervical cancer vaccine in women 15-55 years of age.2

Earlier data from this and other studies in girls and women aged 10-55 years demonstrated that all women vaccinated with the vaccine had a strong immune response against the two most common cancer-causing human papillomavirus types.2,3,4 "This vaccine could potentially protect women of all age groups against cervical cancer" explains Professor Schwarz.

Neutralising antibodies - key for protection

CervarixTM has shown to induce consistently high levels of neutralising antibodies against virus types 16 and 18, for over 5.5 years in women 15-25 years of age, according to a second study presented at IPC.5 The data is drawn from an ongoing phase II study. Other data from this study indicated 100 percent efficacy against precancerous lesions due to virus types 16 and 18 for over a period of 5.5 years.4 It is therefore believed that neutralising antibodies play an important role in protection.

This is the longest duration of consistently high immune response shown by a cervical cancer vaccine against the two most common cancer-causing virus types to date.3 GSK's cervical cancer vaccine is the only one that has shown to induce high levels of neutralising antibodies against both virus types 16 and 18 over 5.5 years.4

Protecting against virus types 16 and 18 and beyond

The burden of virus types 16 and 18 is huge, but the risk of cervical cancer extends beyond these two types.6 Virus types 45 and 31 cause up to 10 percent of cervical cancer cases globally.6 Together, virus types 16, 18, 31 and 45 account for 80 percent of cervical cancer cases worldwide.6

Phase II data indicate that CervarixTM is the only cervical cancer vaccine that provides strong protection specifically against incident infection caused by two additional cancer-causing virus types (31 and 45) for over 5.5 years, in addition to 100 percent protection against precancerous lesions due to virus types 16 and 18 over the same period of time.4 Later phase III data reinforced these findings by demonstrating that GSK's cervical cancer vaccine provides 100* percent protection against advanced precancerous lesions caused by virus types 16 and 18, and significant protection against 6-month persistent infection caused by virus types 45 and 31.7

  Burden of cancer

Despite the positive impact of screening in a number of countries, women continue to be at risk.8 Annually 270,000 women die of cervical cancer around the world, which equates to one every two minutes, making it the third leading cause of cancer death among women globally.9 There are currently over 1.4 million women diagnosed with cervical cancer worldwide.9 Additionally women who receive abnormal screening results can experience significant anxiety and uncertainty.10,11

* In this study of women including those with other oncogenic HPV infections and low-grade abnormal cytology at entry there was 90 percent efficacy against CIN2+ associated with HPV 16/18 DNA in the lesion. Many of the CIN2+ lesions were associated with multiple HPV types. There was 100 percent efficacy against CIN2+ considered causally related to HPV 16/18 in an additional analysis taking account of the likely causal role of persistence of oncogenic HPV infection prior to lesion development).7

About Cervarix™ (Human Papillomavirus Vaccine [Types 16, 18] (Recombinant, adjuvanted adsorbed))

Cervarix™ is indicated in the EU for the prevention of high-grade cervical intraepithelial neoplasia (CIN grades 2 and 3) and cervical cancer causally related to Human Papillomavirus (HPV) types 16 and 18.11

In May 2007, Cervarix™ was granted its first licence in a major market by the Therapeutic Goods Administration (TGA) of Australia for the prevention of cervical cancer and precancerous lesions caused by human papillomavirus types 16 and 18 for use in females ages 10 to 45 years.12 Subsequent licenses have been granted in the Philippines, Kenya and the United Arab Emirates.

GSK was granted Community Marketing Authorisation in Europe on the 20th September 2007 and submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its cervical cancer candidate vaccine in March 2007. Other regulatory filings include many additional countries in Africa, Asia and Latin America.

About cervical cancer

Cervical cancer is the second most common cancer in women under 45 and a significant cause of death and of much emotional and physical distress in women.13,14 It occurs when infection with the human papillomavirus becomes persistent, and progresses to cancer. Up to 75 percent of sexually active women will acquire a human papillomavirus infection in their lifetime, with the risk of persistence increasing with age.15,16,17

Approximately 100 types of human papillomavirus have been identified to date and, of these, approximately 15 virus types are considered to cause cervical cancer 18,19. Virus types 16 and 18 are responsible for approximately 71.5 percent of cervical cancers in Europe.18

About GlaxoSmithKline and GlaxoSmithKline Biologicals

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, please visit http://www.gsk.com/media.

GSK Biologicals (GSK Bio), one of the world's leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline's activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world - an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination paediatric vaccines which protect the world's children from up to six diseases in one vaccine.

Cervarix™ is a trademark of the GlaxoSmithKline group of companies.

References

1. Poncelet S, Cambron S, Giannini SL et al. Induction of Cervical Mucosal HPV IgG in Women 15-55 Years Old Following Systemic Vaccination with GSKs prophylactic Cervical Cancer Candidate Vaccine. Presented at IPC 2007 (ref tbc)

2. Schwarz T, Dubin G, et al. Human Papillomavirus (HPV) 16/18 L1 AS04 virus-like particle (VLP) cervical cancer vaccine is immunogenic and well-tolerated 18 Months after vaccination in women up to age 55 years. Presented at ASCO Annual Clinical Meeting, 1-5 June 2007

3. Rombo L, Dubin G. Long-term safety and immunogenicity of a cervical cancer candidate vaccine in 10-14-year-old adolescent girls. Presented at the European Society of Paediatric Infectious Diseases (ESPID) annual meeting on 2-5 May 2007

4. Gall SA, et al. Substantial impact on precancerous lesions and HPV infections through 5.5 years in women vaccinated with the HPV-16/18 L1 VLP AS04 candidate vaccine. Presented at the American Association for Cancer Research (AACR) annual meeting, 14-16 April 2007 (abstract no. 4900)

5. Dessy F, David MP, Schuind A et al. Evaluation of HPV neutralizing antibodies from an extended follow up study through 5.5 years in women vaccinated with GSKs prophylactic Cervical Cancer Candidate Vaccine. Presented at IPC 2007 (ref tbc)

6. Munoz N, Bosch X, Castellasague X. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004; 111: 278-8504

7. Paavonen, J., Jenkins, D., Bosch, X., et al. Efficacy of a human papillomavirus (HPV)-16/18 L1 virus-like particle (VLP) AS04 vaccine: a phase III randomized, controlled trial in young women. The Lancet 2007; 369: 2161-2170

8. Sankaranarayanan R, Gaffikin L, Jacob M, et al. A critical assessment of screening methods for cervical neoplasia. Int J Gynaecol Obstet 2005; 89 Suppl 2: S4-S12.

9. Ferlay J, Bray P, Pisani P, et al. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 2.0. IARCPress, Lyon, 2004. Available at: http://www-dep.iarc.fr. Accessed September 20, 2005

10. Bell S, Porter M, Kitchener H, Fraser C, Fisher P, Mann E. Psychological response to cervical screening. Prev Med 1995; 24: 610-616

11. Approved European Cervarix Summary Of Produce Characteristics - September 2007

12. Australian Cervarix Product Information - May 2007

13. Lerman C, Miller SM, Scarborough R, Hanjani P, Nolte S, Smith D. Adverse psychologic consequences of positive cytologic cervical screening. Am J Obstet Gynecol 1991; 165: 658-662

14. Basen-Engquist K, Paskett ED, Buzaglo J et al. Cervical cancer. Cancer 2003; 98: 2009-2014

15. Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer-burden and assessment of causality. J Natl Cancer Inst Monogr 2003; 31: 3-13.

16 Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med 1997; 102: 3-8.

17. Castle PE et al. A prospective study of age trends in cervical cancer human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. JID 2005: 191: 1808-1816.

18. Muñoz N et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. New England Journal of Medicine 2003; 348: 518-527

19. Walboomers JM et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12-19

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