In trials, two groundbreaking, Dartmouth-developed vaccines have proven 100 percent effective in preventing HPV-caused cervical cancer. The vaccinations act against HPV-16 and 18, which are responsible for 70 percent of all cervical cancers worldwide.
The National Cervical Cancer Coalition estimates that 14,000 women in the United States are diagnosed with cervical cancer each year and more than 3,900 die annually.
Pharmaceutical company Glaxo-SmithKline's test vaccine labeled Cervarix is still in the midst of its third phase of trials, which consists of thousands of women worldwide, while drug company Merck is conluding its third phase on Gardasil this year. Gardasil awaits approval from the Food and Drug Administration, which is expected to rule on the vaccine on June 8. After FDA approval, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices is expected to rule on the appropriate age groups of females who will be immunized.
"The timeline has been incredibly accelerated," says Dr. Diane Harper, a professor at both the College and Dartmouth Medical School. She predicts that both vaccines will be available in the United States by 2008 and possibly as early as 2007.
Harper was part of a group of HPV experts that Merck and GlaxoSmithKline consulted with when they first received the basic vaccine technology from virologists at the University of Rochester, the National Institute of Health and in Australia in the early 1990s. As one of the main consultants for the vaccines, Harper was the main factor in bringing the vaccine development to Dartmouth.
"In the vaccine world, 100 percent efficacy is unheard of," Harper said. "What this means is that we have the potential to eradicate cervical cancer just like we have eradicated smallpox."
Harper is the Principal Investigator for both Merck and GlaxoSmithKline's trials at Dartmouth. In this position, Harper assumes full responsibility for the trials and reports to the Committee for the Protection of Human Subjects, ensuring that all trials conform to strict human rights principles.
Developing revolutionary vaccination technology has not come cheaply. The phase two and three trials combined have cost Merck and GlaxoSmithKline approximately $100 million each to set up clinical sites worldwide, reimburse volunteers for their time, hire study workers and administrators and administer and monitor the vaccinations. These figures don't even include the pharmaceutical giants' costs for manufacturing the vaccines, reading Pap smears and developing the tests for the HPV types from cells and from blood.
In addition to gaining worldwide recognition for its part in cancer history, Dartmouth typically institutes an overhead of 20 to 60 percent of a project's budget for its trials at the school. The College's budget office negotiates with organizations, in this case pharmaceutical companies, the exact percentage it requires from the trial or trials, which in this case had a Dartmouth budget of about $1 million for each trial. The majority of the money in these types of trials, Harper explained, goes to reimbursing the patients for their time and the study operators for their work.
Despite its groundbreaking efficacy in the fight against cervical cancer, however, there remain a few obstacles to the widespread use of Cervarix or Gardasil in the next few years. Harper cites the initial cost of the vaccines as expensive, about $300 to $500 for three doses. Yet she emphasizes that the cost of treating HPV infections and cervical cancer far exceed those of the new vaccines.
The differences between the vaccines appear negotiable but may prove extremely important once girls start receiving the vaccinations at ten years old, which is the age Harper predicts the CDC will advocate for immunization.
In addition to providing 100 percent protection against the top two cancer-causing HPV viruses Cervarix has also been proven 95 percent effective against HPV-45, a cousin of 18, and 50 percent effective against HPV-31, a cousin of 16 -- results the Merck drug Gardasil has not demonstrated. Instead, Gardasil prevents HPV-6 and 11, which cause genital warts. Cervarix's protection against 16, 18, 31 and 45 means the vaccine is effective against all of the top four cancer-causing types of HPV.
Gardasil is constructed from the HPV "outer shell" protein minus its harmful DNA and the alum adjuvant that has been the basis of vaccinations for other diseases. However, as with other vaccinations based on the same alum adjuvant, disease prevention after vaccination wanes after 3.5 years, which suggests women may require a booster shot every ten years.
The varying efficacy periods of the vaccinations mean that if ten-year-old girls receive Gardasil, they will require a booster shot near the age of 20 -- precisely when women are at their peak acquisition of HPV infection. Harper has advocated vaccination at the age of 15, which would ensure that even using Gardasil, young women would be completely protected from HPV-induced cervical cancer during their most at-risk period, between 15 and 25 years.
With the abnormal Pap smear rate at about 5 percent of the 60 million American women who get them each year, Harper estimates that once the vaccinations are in place, American women will undergo half the Pap smears they do now. They will require fewer Pap smears overall, as well as fewer in follow-ups to abnormal test results. Physicians tend to follow the rule that three years in a row of normal annual Pap smears indicates that a woman can safely move to having the procedure every three years.
"Literally, there is no other advance in women's health in the past 50 years that has been such a huge development," Harper says. "The vaccine is just truly phenomenal."
