Cervical Cancer Vaccine
One of the greatest breakthroughs in the entire history of cancer prevention has its origins in research done by three virologists at the University of Rochester Medical Center. Richard Reichman, M.D., William Bonnez, M.D., and Robert Rose, Ph.D., discovered a method to protect against several strains of human papillomavirus (HPV), including those that cause the most prevalent forms of cervical cancer. This research led Merck & Co. to develop Gardasil®, the first pure anti-cancer vaccine, approved by the U.S. Food and Drug Administration (FDA) in June, 2006.
Cervical Cancer and HPV
Cervical cancer is the second leading cause of cancer deaths in women around the world, killing about 250,000 annually. In America, about 10,000 women are diagnosed with it annually and about 4,000 die from it. The Pap test, an early detection technique developed some fifty years ago, has successfully reduced the number of deaths in the developed world.
HPV is now recognized as the major cause of cervical cancer. In fact, HPV is the world’s most common sexually transmitted infection; about 75% of sexually active people will get an HPV infection at some time. There are more than 100 strains of HPV, and nearly everyone comes in contact with one strain or another. Some cause common warts on the hands or plantar warts on the feet. At least 40 types of HPV can infect the genitourinary system.
But most cases are not at all serious; the body fights off the virus and the people don’t even know they were infected. However, at least four types of HPV (types 6, 11, 16 and 18) cause genital warts, and two of those (16 and 18) cause about 70 percent of cervical cancers. These four types are the targets of the new vaccine.
The New Vaccine
Gardasil was approved by the FDA for use in girls and women ages 9 to 26. It’s given in three doses, each an injection in the upper arm or upper thigh. The second dose follows two months after the first; the third is six months after the first. The vaccine works by causing the body to produce antibodies that fight HPV.
The Advisory Committee for Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC) recommends that to be most effective, the vaccine should be given to girls between the age of 9 and 13. Ideally, they should get the vaccine before they are sexually active. This is because the vaccine is most effective in girls/women who have not yet acquired any of the four HPV types covered by the vaccine.
Females who are sexually active may also benefit from the vaccine. But they may get less benefit from the vaccine since they may have already acquired one or more HPV type(s) covered by the vaccine. Few young women are infected with all four of these HPV types. So they would still get protection from those types they have not acquired. Currently, there is no test available to tell if a girl/woman has had any or all of these four HPV types.
The vaccine will be included in the government’s Vaccines for Children (VFC) program, which gives free vaccines to children up to age 18 who are Medicaid-eligible, uninsured, underinsured or Native American. But it is up to individual states to decide if a vaccine becomes mandatory for school children.
Extensive clinical trials of the vaccine also showed definite disease reducing benefits to women ages 13 to 26, including sexually active ones who were already infected with the four types of HPV.
Internationally, Gardasil has been approved for use in more than 30 countries including those in the European Union, Mexico, Malaysia, Australia, Taiwan, Canada, New Zealand and Brazil, and is under review in 50 others. Further, the international non-profit organization, PATH, dedicated to improving human health in the poorest nations, plans to work with the vaccine makers to introduce them to the developing world and to set up pilot programs in India, Peru, Uganda, and Vietnam in 2007.
The Path to the Vaccine
As is often the case in science, the vaccines can be called “accidents,” unexpected consequences that were not the researchers’ original goal. The research itself followed a tangled trail of frustrations and false starts, and involved both cows and clergymen.
It all began more than twenty years ago, when Reichman, Bonnez, and Rose were looking for a blood test to diagnose HPV infection and a treatment for the genital warts it can produce. To make a blood test work, they needed to find an HPV antigen, the substance that causes the immune system to produce antibodies. But HPV is difficult to study because it doesn’t grow in the lab and human genital warts don’t contain enough antigens.
So, as is also often the case, the researchers turned to animals, in this case to cows. Bonnez visited farmers, veterinarians and slaughterhouses, collecting cow warts from which the team could extract BPV, bovine papillomavirus. The next step was to see if BPV would work as an antigen. To do this, the researchers needed blood samples from a control group of people who had never been infected with HPV. That’s were the clergy came in, celibate priests and nuns who confided that they had not been sexually active before entering their vocation.
Though the work with BPV did produce valuable data, it did not lead to the diagnostic blood test hoped for. So the trio turned to other animal models, mice and moths. They studied the effects of HPV in mice, and how the mice responded to the HPV by producing antibodies to fight against it. Then they developed a way to trigger that immune response in other animals.
They put an HPV gene into moth cells using a virus called baculovirus, which infects insects. The HPV gene produced particles called VLPs, virus-like particles. They look like real HPV particles, but are harmless. Most important, they caused the immune system of test animals to produce those HPV fighting antibodies. And along the way they realized this could lead to something more valuable than a diagnostic blood test: a vaccine.
To develop a vaccine that would work on humans and do clinical studies of it, the
Rochester virologists partnered with Medimmune, a small Maryland pharmaceutical company. Medimmune later sold the vaccine rights to GlaxoSmithKline. Another company, Merck & Co. was working on its own vaccine, using research done by other institutions.
But what means most to the researchers is that their work will help save so many lives. As Rose says, “It’s been an amazing life experience … that what we’ve done could affect the world.”