Cancer Vaccine Gears Up for Global Delivery

Photo by Graham Ramsay Erica Seiguer

When we think of vaccines, images come to mind of infectious diseases that have been eradicated or controlled, usually in early childhood. Recently, however, a vaccine that not only prevents infection, but cancer, has been developed.

This past June, the U.S. Food and Drug Administration approved the first vaccine to prevent infection by several strains of the sexually transmitted human papillomavirus (HPV), the cause of most cases of cervical cancer. The vaccine is targeted at strains responsible for 70 percent of the cancers and 90 percent of genital warts. It has been found to be almost 100 percent effective. Yet there are many other HPV strains, making continued screening a priority. Its approval comes with other challenges, too, from questions about how early to vaccinate girls to whether boys and men should be vaccinated to how the relatively expensive vaccine will reach girls in developing countries, where its potential impact is enormous.

World Impact of Cervical Cancer
Genital HPV is the most common sexually transmitted disease in the United States, with up to 50 percent of sexually active men and women becoming infected. According to the Centers for Disease Control and Prevention (CDC), 80 percent of women become infected by age 50. Several strains of HPV, called the “high-risk” types, are known to cause cervical cancer. Despite effective screening with the Pap smear and HPV typing, each year in the United States more than 10,000 cases of cervical cancer are diagnosed and about 4,000 women die from the disease.

These numbers, however, are dwarfed by the impact of the disease in developing countries: of the almost 250,000 deaths worldwide each year from cervical cancer, 85 percent occur in developing countries, making the disorder the second most common cancer in women.

The new product, Merck’s Gardasil, is a quadrivalent human papillomavirus recombinant vaccine that will prevent infection with HPV types 6, 11, 16, and 18, known to cause cervical cancer, precancerous genital lesions, and genital warts. The vaccine is licensed for use in girls age 9 to 26, and in late June, the CDC’s Advisory Committee on Immunization Practices recommended that it be routinely given to girls ages 11 and 12. The intervention has taken years to develop and several clinical trials involving tens of thousands of girls and women. In order to be optimally effective, girls need to be vaccinated prior to exposure with any of the four viruses.

Merck has pledged to work with poorer nations to ensure delivery of the vaccine, and the Bill and Melinda Gates Foundation has already begun groundwork to assess local capacity and ensure adequate vaccine financing and delivery systems. The foundation recently announced a five-year, $27.8 million grant to PATH, an international nonprofit organization, to coordinate with international agencies, government officials, and both Merck and GlaxoSmithKline (which hopes to introduce a second HPV vaccine, Cervarix, in the next year). The grant provides funding for research and demonstration projects in India, Peru, Uganda, and Vietnam and aims to provide evidence for regional and global introduction of the vaccine. PATH will launch its pilot demonstration projects in the four selected countries as soon as a vaccine is licensed in each.

Access on the Ground
Dr. Jacqueline Sherris, director of the cervical cancer program at PATH, recognizes that the introduction of Gardasil will pose unique challenges. PATH has been working with both Merck and GlaxoSmithKline on the introduction of the vaccine and reports that both manufacturers have publicly announced that they are committed to tiered pricing—marketing the drug at lower prices in regions where the $360 price tag is prohibitive.

Even so, for countries currently paying about $1 per dose for many vaccines, even heavily discounted prices will require major commitments from ministers of health and finance. PATH, according to Sherris, plans to “work iteratively with the manufacturers, governments, and funding agencies so that countries and manufacturers can make determinations about the most appropriate price.” She notes that in the long term, developing-country manufacturers likely will enter the market, at which point the price of the vaccine will decline even further.

The PATH project does not have a formal relationship with the Global Alliance for Vaccines and Immunization (GAVI), though it is tasked with developing an investment case for GAVI and other donors. A critical challenge is pure logistics: how to get a vaccine to children age 10 to 14, the likely target group. There are currently very few vaccine programs that reach 10- to 14-year-olds anywhere, and few health programs that intervene with this age group, as opposed to well-established programs aimed at groups such as newborns, infants, and pregnant women.

In countries where it is reasonable to vaccinate at school, the strategy may be relatively straightforward. PATH is also considering studying alternative dosing regimens to the one studied by Merck, which has the second and third doses administered at two and six months. For countries with semiannual health outreach days, dosing at six and twelve months may be more feasible.

It is this kind of flexible, tailored approach to vaccine delivery that PATH looks to provide to governments and donors, with the hope that detailed data on individual health care systems will translate into widespread immunization with the first vaccine aimed specifically at women’s health and the first true cancer vaccine.

—Erica Seiguer is an MD–PhD student studying economics in Harvard’s Doctoral Program in Health Policy.

Related Websites
PATH: www.path.org
Bill and Melinda Gates Foundation: www.gatesfoundation.org
Alliance for Cervical Cancer Prevention: www.alliance-cxca.org

The opinions expressed in this column are not necessarily those of Harvard Medical School, its affiliated institutions, or Harvard University.

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