Maureen Lafrenière

In March 2007, the Government of Canada announced a three-year, $300-million program to help provinces and territories vaccinate women and girls against human papillomavirus (HPV), a pathogen implicated in the development of cervical cancer. The program, which targets 9- to 13-year-old girls who have not yet become sexually active, followed a recommendation from the federal government’s National Advisory Committee on Immunization (NACI).

While cancer prevention strategies are always welcome, reaction to this vaccine and its application is divided. Some question the benefit of universal vaccination as the main strategy to decrease the incidence of cervical cancer, a relatively rare disease in North America. Other concerns involve the vaccine’s cost, its long-term efficacy, its impact on sexual behaviour and the political lobbying for public funding.

Gardasil® — manufactured by Merck & Co., Inc.(1) — is the only HPV vaccine currently licensed in Canada and the United States, although approval of a similar product by competitor GlaxoSmithKline is anticipated soon. Approved by Health Canada in 2006 for females aged 9 to 26, Gardasil protects against four strains of HPV, two of which are implicated in cervical cancer.

The HPV-cervical cancer connection
HPV is a common virus that infects many body parts, can cause warts or cellular abnormalities, and these, in turn, sometimes result in malignancies. There are more than 100 known strains of HPV only some of which are transmitted sexually; of these, at least 15 types are classified as a high oncogenic risk. Although HPV is widespread — studies suggest that up to 75% of sexually-active Canadians may be infected at some point in their lives — most infections clear up spontaneously, i.e., 70% within 12 months and 90% within 2 years. This includes high-risk strains.(2)

Studies indicate that Gardasil provides effective protection against two high-risk strains of HPV associated with 70% of cervical cancer cases, and two low-risk types known to cause about 90% of anogenital warts. Since the vaccine does not protect against all high-risk strains, regular Pap testing remains important for vaccinated women.

A preventable cancer
Cervical cancer usually develops slowly over a period of years; when accessible testing and adequate public education are in place, screening and intervention are highly effective at detecting and halting progress of the disease. The U. S. Centers for Disease Control declared in 1999 that “…screening younger women is an important strategy that actually prevents cervical cancer from ever developing.”(3) The Canadian Women’s Health Network has stated that “deaths associated with cervical cancer … must be considered as a failure in the adequate support of both the primary care and reproductive health services that would … ensure all women get appropriate Pap testing and follow-up.”(4)

Incidence of cervical cancer
The Canadian Medical Association projects an estimated 1300 new cases and 450 deaths from cervical cancer for 2007, making the disease the 11th most common cancer and the 13th in cancer mortality for Canadian women.(5) This compares to 22,300 new cases and 5,300 deaths for breast cancer for the same period.(6)

Worldwide, however, cervical cancer is the second most common form of cancer in women and the first in many developing countries, accounting for more than 250,000 deaths annually. Its incidence relates inversely to the availability of screening, follow-up treatment and public education. Exacerbating factors may include the presence of epidemic HIV infection and, in some cases, a cultural reluctance to participate in screening.(7) Regional and cultural disparities also exist in North America, with African-American, aboriginal and a few other cultural minorities experiencing mortality rates between two and ten times that of the general population.(8,9)

Specific concerns
The debate over universal vaccination for HPV involves several medical and social issues, including:

1. Cost and cost-benefit: At just over $400 CD per treatment, Gardasil has been called “the most costly vaccine on the planet.”(10) Some within the medical community are concerned that the allocation of public funding to mass vaccination risks diverting limited resources from other important clinical and research programs, particularly with respect to “the needs of the marginalized and most vulnerable groups in society.”(11)

2. Calls for more clinical information: Knowledge about long-term effectiveness of the vaccine is lacking because of the limited duration of the clinical trials, now about 5.5 years. Although protection from viral infection could be measured within this period, the effectiveness of the vaccine against cervical cancer as a final outcome could not. The rate at which vaccine potency declines and the need for booster shots to maintain long-term immunity are not known.(12) Moreover, only a small number of 9- to 12-year-old girls was enrolled in the trials — the target age group for the vaccination program — with some of the youngest followed for as little as 18 months.(13)

Some other issues not yet studied include potential changes in the distribution or dominance of other oncogenic strains (if the targeted HPV strains are successfully suppressed by mass vaccination), the value of vaccinating males, possible immunization or therapeutic treatment for women already infected by HPV (the vaccine is ineffective for those already exposed to the virus) and the inclusion of population sub-groups in trials.(14)

3. Potential misconceptions: There are concerns that vaccination for HPV may impart a false sense of security resulting in less attention paid to regular screening and to safe sexual practices. The promotion of Gardasil as the “cervical cancer vaccine” or “anti-cancer vaccine” might mislead some about the extent of the vaccine’s protection, or even about which cancers are involved, despite the abundance of information available. The National Cervical Cancer Coalition (U. S.), warns vaccinated women not to neglect screening, mentioning on its website that “some … have thought that a Pap test is no longer necessary.”(15)

4. Marketing and lobbying. The US Food & Drug Administration approval of Gardasil was preceded by an extensive advertising campaign presenting cervical cancer as an immediate and serious health problem.(16,17) Intense lobbying for the rapid adoption of mandatory school-based vaccination programs followed approval of the vaccine, but was abandoned after negative public reaction. In Canada, the federal government chose to finance a major program after it was recommended by the NACI, but before completion of an assessment by the Canadian Immunization Committee, a federal government body mandated to determine cost-effectiveness and efficacy of new products in routine immunization programs.(18)

Provincial and territorial vaccination programs
Some provinces have begun to make the vaccine available free of charge to girls through schools or family doctors, while others are planned or under discussion. Following is a summary based on information available in February 2008. An estimated 3.8 million Canadian girls are candidates for the vaccine.(19)

(Dates below indicate when vaccination is/was to begin.)

Newfoundland — grade 6 — fall 2007
Nova Scotia — grade 7 — fall 2007
Prince Edward Island — grade 6 — fall 2007
New Brunswick — grades 7 and 8 — fall 2008
Quebec — from grade 4, details not available — fall 2008
Ontario — grade 8 — fall 2007
Manitoba — grades 4–8, details to be announced — March 2008
Saskatchewan — available publicity by appointment — 2007
Alberta — available privately; not covered by public system — April 2007
British Columbia — grade 6, with catch-up for grades 7, 8, and 9 over 3 years — fall 2008
Nunavut — available privately; not covered by system — fall 2007
Northwest Territories — information not available
Yukon — available privately — fall 2007

References:

1. N. B.: The Canadian subsidiary of the company is called Merck Frosst Canada Ltd.
2. Public Health Agency of Canada, Human papillomavirus prevention and HPV vaccine [www.phac-aspc.gc.ca] & National Cancer Institute [www.cancer.gov]
3. Lee, N., Testimony on Cervical Cancer before the House Committee on Commerce, Subcommittee on Health and Environment, 1999.
4. Lippman, A., Melnychuk, R. Shimmin, C. & Boscoe, M. Human papillomavirus, vaccines and women’s health: questions and cautions. Canadian Medical Association Journal, August 28, 2007. [www.cmaj.ca]
5. ibid.
6. Canadian Cancer Society, April 2007 [www.cancer.ca]
7. Katz, I.T. & Wright, A.A. : Preventing Cervical Cancer in the Developing World. New England Journal of Medicine, March 16, 2006 [www.nejm.org]
8. see 2.
9. CDC — National Centre for Chronic Disease and Health Promotion [www.cdc.gov]
10. Gardasil: the cancer vaccine that protects against STD. CBC News, June 21, 2007 [www.cbcnews.ca]
11. (The Varivax chicken pox vaccine, also from Merck, costs $75.) Talaga T., Lobbyists boosted vaccine program, The Toronto Star, August 16, 2007. See also 4 above.
12. see 4 above.
13. Sawaya, G. & Smith-McCune, K., HPV Vaccination — More Answers, More Questions. New England Journal of Medicine, May 10, 2007
14. Canadian Agency for Drugs and Technologies in Health: Bulletin, issue 109, December 2007 [www.cadth.ca]
15. National Cervical Cancer Coalition [www.nccc-online.org]
16. Merck Inc.’s “One Less” campaign can be viewed at www.gardasil.com
17. 17. Siers-Poisson, J., The Politics and PR of Cervical Cancer—a series of 4 articles (available at www.prwatch.org)
18. Picard, A., How politics pushed the HPV vaccine. The Globe & Mail, August 11, 2007 [www.globeandmail.com]
19. see 15.

Other sources:
Immunize females aged 9 to 26 against HP: advisory committee. Canadian Press, 30 Jan 2007 [www.cbcnews.ca]

Harrold, M. HPV vaccine on the way, The Montreal Gazette, September 27, 2007 [www.cbc.ca]

Centers for Disease Control, National Centre for Chronic Disease and Health Promotion [www.cdc.gov]

Note: Special thanks go to Dr. Peter Weldon for his help in sorting through and making sense of the overwhelming amount of information on this topic.