GlaxoSmithKline response re HPV vaccine testing in India
9 Feb 2010
Business & Human Rights Resource Centre invited GlaxoSmithKline to respond to the following item:
- “Women's organisations oppose HPV vaccines „against cervical cancer‟”, Saheli Women's Resource
Centre and Sama Resource Group for Women & Health, 28 December 2009:
In response, GlaxoSmithKline sent the following statement:
―GlaxoSmithKline (GSK) thanks the Business & Human Rights Council for the opportunity to
respond the comments made by the Saheli Women's Resource Centre and Sama Resource
Group for Women & Health. Below is factual, published and referenced information about
Cervical Cancer and GSK’s vaccine to prevent Cervical Cancer.
About Cervical Cancer:
Cervical cancer develops as a result of persistent infection with a cancer causing virus known as
human papillomavirus (HPV) 1. The human papillomavirus is extremely common and it is easily
transmitted from skin-to-skin contact in the genital area1,2. The virus can be acquired without full
sexual intercourse2. Condoms are a helpful preventive measure but do not fully protect women
from acquiring the human papillomavirus3. Approximately 100 types of human papillomavirus
have been identified in humans to date. Of these, only 15 virus types are considered to cause
cervical cancer4. Virus types 16 and 18 account for more than 70 percent of all cervical cancer
cases globally4 and 82.5% of cervical cancer in India5.
? Vaccine against Cervical cancer is in the national immunization program of many
countries around the world, including UK, US, Australia and most of the European countries.
About GlaxoSmithKline’s vaccine to prevent Cervical Cancer:
Cervarix® is designed to offer women protection against cervical cancer. Cervarix® provides
protection against the most common cancer-causing virus types — HPV 16 and 186, 7. These
virus types are responsible for over 70 percent of all cervical cancer cases worldwide8. Cervarix®
provides further evidence of cross-protection against infection with cancer-causing virus types 31,
33 and 459.
? Virus types 16, 18, 31, 33 and 45 are collectively responsible for up to 81.8 percent of
cervical cancer cases worldwide4.
? In June 2009, the WHO granted prequalification for Cervarix®. This means the vaccine
can be purchased by UN agencies and the GAVI Alliance in partnership with developing
? To date GSK’s vaccine against HPV, Cervarix® has been approved in over 100 countries
around the world, including the 27 member states of the European Union (EU), Australia, Brazil,
South Korea, Mexico, Taiwan, Japan and the United States.
? Since its launch in 2007, Cervarix has been administered to millions of women. The
vaccine has been selected for immunisation programmes in five countries, including national
programmes in the Netherlands and the UK and regional programmes across Italy, Poland and
Cervical cancer develops several years after the infection is acquired, studies have shown that
vaccination provides optimal protection if administered before acquisition of oncogenic HPV
infection. Moreover, effectiveness of a vaccine is measured on the basis of its ability to protect
against CIN2+ lesions.
? As per results of two Clinical Studies conducted for Cervarix® published in 2009, it is
confirmed that the vaccine:
(1) Offers protection against five of the most common cancer-causing virus types
(2) Provides high and sustained antibody levels for at least 7.3 years till date
Results from the largest global efficacy trial of a cervical cancer vaccine, involving 18,644 women
and published in The Lancet showed that Cervarix® offers Protection’ against the five most
common cancer-causing virus types9.
The study showed that in women who complied with the trial protocol procedures (87 percent of
the total sample), the vaccine provided 92.9 percent protection against cervical pre-cancers
(cervical intraepithelial neoplasia 2+ or CIN 2+) associated with HPV 16 or 18. A further analysis
of the same cohort which excluded lesions not likely to be caused by HPV 16 and 18 revealed
that the vaccine was 98.1 percent effective against cervical pre-cancers (CIN 2+) caused by
these two types9.
The study also showed — for the first time for any cervical cancer vaccine — that Cervarix®
provided significant cross-protection against pre-cancerous lesions not containing HPV types 16
and/or 189. This additional efficacy could translate into approximately 11-16 percent extra
protection against cervical cancer over and above the protection afforded by efficacy against
HPV 16 and 18 alone9. This effect was mainly driven by protection against HPV types 31, 33 and
A long term follow up study- showed that GSK`s Cervarix® provided high and sustained antibody
levels against HPV 16 and HPV 18 through the 7.3 years of follow up after vaccination. This is
the longest follow up reported to date for any licensed HPV vaccine10.
? Cervarix® contains an innovative, proprietary adjuvant called AS04 which induces a
higher and more sustained immune response compared to a conventional adjuvant11.
Adjuvants are substances commonly used in vaccines to enhance the immune response to an
antigen. The higher the antibody levels are following vaccination, the higher they are expected to
HPV is a challenging virus that evades the body’s natural immune system and it is therefore
important an HPV vaccine induces high and sustained levels of the right type of antibodies12, 13.
Cervarix® induces high and sustained antibody levels including neutralising antibodies14 –
antibodies that are considered to be a mediator of protection provided by cervical cancer
vaccines against HPV15. Furthermore, these antibodies in the blood can transfer to the cervix
16– the site of infection where they are most needed to block the virus from entering the cells17.
Safety and tolerability
Cervarix® is generally well-tolerated. An integrated safety analysis of Cervarix® performed in
almost 30,000 women aged 10-72 years from ethnically and geographically diverse backgrounds
over a period of up to 5.5 years has shown no clinically significant differences in serious adverse
events in women vaccinated with Cervarix® compared to the control group18.
In a more recent analysis of safety data reported over a period of 7.4 years in over 57,000
women aged nine years and above, of which over 33,000 received at least one dose of
Cervarix®, the reactogenicity and safety profile of the vaccine was shown to be clinically
acceptable, further supporting the safety profile of Cervarix®19.
WHO recognizes the importance of cervical cancer and other HPV-related diseases as global
public health problems.
Given below are a couple of points from WHO Position Paper 10 April 2009:
WHO recognizes the importance of cervical cancer and other HPV-related diseases as global
public health problems and recommends that routine HPV vaccination should be included in
national immunization programmes, provided that: prevention of cervical cancer or other HPV-
related diseases, or both, constitutes a public health priority; vaccine introduction is
programmatically feasible; sustainable financing can be secured; and the cost effectiveness of
vaccination strategies in the country or region is considered. (Ref.: WHO position paper 10 April
2009, Attached file)
Since the immunological correlates of vaccine protection are unknown and the development of
cervical cancer may occur decades after HPV infection, regulatory authorities have accepted the
use of CIN grade 2 or 3 (CIN2–3) and AIS as clinical end-points in vaccine efficacy trials instead
of invasive cervical cancer. Also, using cervical cancer as the outcome in such trials is precluded
for ethical reasons. Precancerous lesions usually develop <5 years after HPV infection. If
untreated, CIN2–3 has a high probability of progressing to squamous cell cancer, and AIS has a
high probability of progressing to adenocarcinoma. The time between initial HPV infection and
development of cervical cancer averages 20 years. (Ref.: WHO position paper 10 April 2009,
1. Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections J Clin Virol 2005;
32 Suppl 1; S16-24
2. Schiffman M, Kjaer SK. Natural history of anogenital human papillomavirus infection and
neoplasia. J Natl Cancer Inst Monogr 2003; 31: 14-19
3. Winer RL, Hughes JP, Feng Q et al. Condom use and the risk of genital human papillomavirus
infection in young women. N Engl J Med 2006 June 22;354(25):2645-54.
4. Bosch FX et Al. Epidemiology and natural history of Human Papillomavirus Infections and Type-
Specific Implications in Cervical Neoplasia. Vaccine 26S (2008) K1–K16.
5. WHO/ICO information Centre on HPV and Cervical cancer. Summary report on HPV and cervical
cancer statistics in India 2010. [ 04/02/2010]
6. Cervarix™ Product Information 2007 [TBC]
7. Harper DM et al. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18
AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet. 2009
Dec 12; 374(9706):1975-85.
8. Muñoz N, et al. Against which human papillomavirus types shall we vaccinate and screen? The
international perspective. Int. J Cancer 2003; 111: 278-285
9. Paavonen J et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against cervical infection
and pre-cancer caused by oncogenic HPV types: final event-driven analysis in young women (the
PATRICIA trial). 2009. Published online, The Lancet July 7 2009
10. De Carvalho N et al. Immunogenicity and safety of HPV-16/18 AS04-adjuvanted vaccine up to
7.3y. Abstract presented at the 25th International Papillomavirus Conference (IPV) 8-14 May 2009; Malmo,
11. Giannini SL, Hanon E, Moris P et al. Enhanced humoral and memory B cellular immunity using
HPV 16/18 L1 VLP vaccine formulated with the MPL / aluminium salt combination (AS04) compared to
aluminium salt only. Vaccine 2006; 24: 5937-5949.
12. Stanley M. Immune responses to human papillomavirus. Vaccine, 2006; 24 Suppl 1:S16-22.
13. Tindle RW. Immune evasion in human papillomavirus-associated cervical cancer, Nat Rev Cancer,
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 Cervarix™ (GSKs HPV 16/18 AS04 Candidate Vaccine). Abstract at The Society of
Gynecologic Oncologists Annual Meeting (SGO), Tampa, Florida, 9-12 March, 2008.
15. WHO. Expert Committee on Biological Standardization. Guidelines to assure the quality, safety
and efficacy of recombinant Human Papillomavirus virus-like particle vaccines, accessed on 27/3/2009 at
16. Stanley M, Lowy DR, Frazer I. Chapter 12: prophylactic HPV vaccines: underlying mechanisms.
Vaccine 2006;24(Suppl 3):S106–13.
17. Schwarz T, Immune response to human papillomavirus after prophylactic vaccination with AS04-
adjuvanted HPV-16/18 vaccine: Improving upon nature. Gynaecologic Oncology. 2008.
18. Descamps D et al. Safety of human papillomavirus (HPV)-16/18 AS04 adjuvanted vaccine for
cervical cancer prevention: integrated summary of 11 clinical trials. Human Vaccines 2009:5:5, 1-9;
19. GSK Briefing Document submitted to the Vaccines and Related Biological Products Advisory
Biologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181371.pdf. Accessed on 25