HPV’s link to cancer was first demonstrated in the early 1980s when German virologist Dr. Harald zur Hausen found that cervical cancer cells contained HPV DNA. Since then, Lowy noted, scientists have learned a lot about the natural history of HPV infections and the genesis of cervical cancer. Zur Hausen’s findings also led to the discovery of other HPV-associated cancers.
Lowy said scientists are using these insights to improve cancer screening. Right now, there are two cervical cancer screening methods: Pap tests and HPV testing. The Pap test identifies changes that might become cancer. HPV tests look for the virus.
Lowy said the second generation of HPV vaccines will prevent more types of HPV infection while requiring fewer doses.
Photos: Bill Branson
One problem with current HPV tests is that they identify infections that do not lead to cervical cancer. Despite this problem, Lowy predicted that HPV-based tests will gradually replace Pap tests as technology advances.
Lowy was involved in developing Cervarix and Gardasil, the first two vaccines approved by the Food and Drug Administration for the prevention of diseases associated with HPV infections. Cervarix is referred to as a bivalent vaccine because it targets two strains, 16 and 18. Gardasil is referred to as a quadrivalent vaccine because it targets strains 6, 11, 16 and 18. According to Lowy, strains 6 and 11 “are responsible for 90 percent of genital warts.”
All children ages 11 or 12 should receive 3 vaccine doses over 6 months. He added that it’s important to vaccinate children before they become sexually active, as HPV infections are common.
Cervarix and Gardasil contain L1, a protein found on the outer shell of HPV strains. Along with his NCI colleague Dr. John Schiller, Lowy discovered that these proteins assemble themselves into virus-like particles—structures that resemble HPV but don’t cause disease. The virus-like particles trigger the immune system to produce antibodies, the immune proteins that eliminate the virus.
Since the vaccines were approved, the FDA has continued to monitor their safety and effectiveness. Lowy said the risk of vaccines causing serious harm is extremely small. He added that while long-term efficacy trials are ongoing, immunity hasn’t waned in the vaccinated population so far.
In the United States, many preteens and teens aren’t getting the vaccine. He attributed this to health care providers not recommending the vaccine to parents. He noted that parents don’t seem concerned about increased sexual activity.
In Australia, where many preteens and teens have been vaccinated, scientists noticed that the incidence of genital warts decreased in the whole population when only girls were receiving the vaccine.
“The prevalence of HPV types that cause genital warts must have gone down and therefore people were just not exposed to it,” he said.
Lowy said the second generation of HPV vaccines will prevent more types of HPV infection while requiring fewer doses. The newer vaccines would be particularly beneficial in developing countries where “about 88 percent of deaths attributable to cervical cancer occur.” He said that in these countries, “It would be logistically so much easier to give fewer doses.”
During the initial HPV vaccine efficacy trials, scientists observed that children under 16 who had received two doses had a stronger immune response compared to older teenagers who received three doses. Lowy said the results led the European Medicines Agency to recommend that two doses be given instead of three. He said the FDA has yet to change its recommendation on dosing.
Recently, the FDA approved Gardasil 9, a vaccine that prevents nine strains of HPV. The 9-valent vaccine includes the next 5 most common HPV strains.
“You can presumably prevent 9 out of 10 potentially oncogenic infections of the cervix,” he said.
Lowy also said it would be possible to safely increase the recommended age for cervical cancer screening if there were high rates of vaccination with the 9-valent vaccine, which would prevent rapidly growing infections.