HPV Vaccine Study in Costa Rica Yields Insights on Cancer Prevention
The HPV vaccine contains virus-like particles (blue) that are noninfectious and stimulate the immune system to produce antibodies (red) that can prevent HPV infections.
A flurry of new research findings on a vaccine that prevents persistent infections by cancer-causing types of the human papillomavirus (HPV) has confirmed the vaccine's efficacy and opened new avenues for research. The results, published in three separate reports, suggest that the vaccine could be simpler to administer and more affordable than researchers had previously thought—and that the vaccine may also have unexpected benefits.
All three studies originate from an ongoing clinical trial of Cervarix in Costa Rica. The new findings could help inform efforts to develop vaccination programs to prevent cervical cancer in countries around the world, the researchers said.
"The results from our trial and from other trials are extremely promising for this vaccine," said Dr. Allan Hildesheim of NCI's Division of Cancer Epidemiology and Genetics (DCEG), a leader of the trial. "And they suggest that the impact of the vaccine may go beyond cervical disease."
HPV infections can lead to cancers of the anus, vagina, vulva, penis, and some oropharyngeal cancers, in addition to cervical cancer. Cervarix is one of two HPV vaccines currently approved by the Food and Drug Administration to prevent these infections; the other is Gardasil.
One of the studies found that fewer than the prescribed three doses of Cervarix may offer the same protection as the full course. If confirmed, this could make vaccination easier to administer and more affordable, factors that are especially important in developing countries that have high rates of cervical cancer.
A second study from the Costa Rica HPV Vaccine Trial found that the vaccine may protect against anal HPV infections that could eventually lead to anal cancer. (See "Clinical Trial Shows Potential Benefit of HPV Vaccine for Anal Cancer.")
Vaccine May Protect against Additional HPV Types
The third study confirmed that the vaccine is highly effective in preventing persistent infections with HPV types 16 and 18—the types targeted by Cervarix. The researchers also found evidence of "cross-protection" against other cancer-causing HPV types not targeted by the original formulation—HPV types 31, 33, and 45.
Testing an HPV Vaccine in the "Real World"
The safety and effectiveness of Cervarix and the other FDA-approved HPV vaccine, Gardasil, were established in clinical trials sponsored by the vaccine makers. Nonetheless, NCI researchers and their long-time collaborators in Costa Rica decided to conduct an independent study of a vaccine in a real-world setting.
A goal of the community-based trial was to collect data that could help with the implementation of cervical cancer prevention programs, said Dr. Herrero. "Our results could help the people who are planning vaccination programs to use this expensive vaccine in the most effective way possible."
Launched in 2004, the randomized trial includes 7,466 women between the ages of 18 and 25 from two Costa Rican communities (approximately one-third of the women in the region). Participants initially received Cervarix or a vaccine against hepatitis A. At the end of 4 years, the researchers offered the HPV vaccine to women in the control group.
The researchers will continue to follow the participants. "This community-based trial provides avenues to study not just the theoretical efficacy of the vaccine but the impact of vaccination on a well-defined population," said Dr. Hildesheim.
"This is a potential additional benefit from vaccination that we had not considered initially," said Dr. Hildesheim, noting that suggestive evidence for cross-protection has been reported previously.
The third study, published online September 9 in Cancer Discovery, also provided further evidence that the benefit of vaccination is greatest when the vaccine is given to young women before they have initiated sexual activity.
"Exposure to HPV occurs as soon as sexual activity begins, so if you start vaccination after that point, you will miss an opportunity to prevent infections," said the study's lead author, Dr. Rolando Herrero, formerly the study director in Costa Rica and now with the International Agency for Research on Cancer.
The findings on age are consistent with previous studies, noted Dr. Kevin Ault of Emory University's School of Medicine, who studies HPV but was not involved in the study. "As you age, you accumulate exposures to HPV, and, if the vaccine is given after you've been exposed to the virus, then it's not going to be effective."
Fewer Doses May Offer Protection
The discovery that two doses—and possibly even one—of Cervarix may protect against infection was possible because the study was done in a "real world" community setting. Many women in the trial (approximately 20 percent) received only one or two doses, often because of pregnancy or an unrelated health problem.
The researchers found, however, that all of the women who received the vaccine were protected equally—at least for the first 4 years after vaccination. Those results appeared online in the Journal of the National Cancer Institute on September 9.
"This study is terrific proof of concept," said Dr. Eduardo Franco of McGill University's Faculty of Medicine, who also studies HPV and was not involved in the research. "It suggests that countries could adopt the suboptimal dose regimens and still receive the same protection as the full course, assuming that the protection against lesions will also hold."
At the end of 4 years, the researchers offered the HPV vaccine to women in the control group. The researchers will follow the trial participants to determine how long the protection lasts.
If the current results are confirmed, the costs of vaccination programs could drop. "Our results may have important implications for public health, although many questions remain unanswered," said the study's first author, Dr. Aimée Kreimer of DCEG.
For instance, how long one or two doses of the vaccine protect against HPV infection is not known. In addition, the findings may not apply to other vaccines or to other populations, such as people who are malnourished or lack strong immune responses, the study authors cautioned.
More Affordable and Sustainable Cervical Cancer Prevention
The Costa Rica HPV Vaccine Trial team in Guanacaste, Costa Rica, at the start of the study in 2004.
"The importance of the current study is not so much for Costa Rica, which has cervical cancer screening programs, but for countries that have truly high incidences of cervical cancer and no screening," Dr. Franco said. More follow-up is needed to show that the suboptimal doses translate into fewer cervical precancerous lesions for vaccinated women, he added.
This study "represents an important step on the road to more affordable and sustainable cervical cancer prevention programs," wrote Dr. Cosette Marie Wheeler of the University of New Mexico in an accompanying editorial.
Few, if any, developing countries where cervical cancer is common can afford vaccination programs, said Dr. Herrero. But if countries can afford to vaccinate only certain groups, they need to know which ones would benefit most, he noted. As the current study shows, this group would likely be young women who are not yet sexually active.
"When we started more than 25 years ago, we were just discovering that HPV was the cause of cervical cancer," said Dr. Herrero. "Today we have a tremendous amount of tools and knowledge, which make it possible to intervene in this disease."
—Edward R. Winstead