WASHINGTON — A human papillomavirus vaccine developed by Merck & Co. is 100% effective in preventing genital warts in women in addition to preventing cervical cancer, Dr. John T. Schiller reported at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.
The vaccine, known as Gardasil, includes HPV types 6, 11, 16, and 18. Types 16 and 18 account for about 70% of cervical cancer, and types 6 and 11 account for about 90% of genital warts, said Dr. Schiller, head of the neoplastic disease section of the National Cancer Institute, Bethesda, Md.
At 2 years of follow-up, Gardasil achieved 100% efficacy against genital warts, vulvar neoplasia, and vaginal neoplasia, in addition to the previously reported 100% efficacy against cervical intraepithelial neoplasia (CIN). The phase II Females United to Unilaterally Reduce Endo-Ectocervical Disease study (FUTURE I) included 2,717 women randomized to a vaccine group and 2,725 randomized to a placebo group. Overall, there were no cases of genital warts in the vaccine group, compared with 40 cases in the placebo group.
Dr. Schiller also shared the latest findings from the FUTURE II study, a randomized, double-blind, phase III clinical trial that included about 12,000 women aged 18–25 years. The intent-to-treat numbers in the FUTURE II study showed extremely strong protection at 2 years of follow-up—only two cases of CIN grade 2 or 3—and the vaccine was generally well tolerated. One case of CIN was associated with HPV type 16, and the other was associated with a combination of types 16 and 18. The phase III studies are ongoing, and the data remain under review, but findings similar to those from the phase II study are expected with regard to genital warts and vulvar and vaginal neoplasia.
Merck filed its Gardasil data with the Food and Drug Administration on Dec. 1, 2005, and a vaccine could be available in the United States by late summer in 2006, Dr. Schiller said. GlaxoSmithKline Inc. has stated that it will seek regulatory approval in 2006 for its vaccine, Cervarix, which immunizes against HPV 16 and 18, but that it might seek initial approval in Europe.
Once the vaccine becomes available, the top candidates for immunization will be 10- to 13-year-old girls. “They are the ideal first targets because presumably, they have not yet been exposed to sexually transmitted viruses,” Dr. Schiller said at the meeting, sponsored by the American Society for Microbiology.
But before the vaccine becomes standard for young girls, it may be used in young women because of the high demand in that population, he noted. Some adult women may not have been exposed to the oncogenic strains of HPV, and vaccination may reduce transmission to their partners as well. An HPV vaccine has yet to be tested in men, but only 10% of HPV cancers occur in men, and high vaccination coverage of women may result in sufficient herd immunity, Dr. Schiller noted.
The HPV vaccines are based on purified viruslike particles (VLPs) that consist of single proteins. They are noninfectious and nononcogenic, but they can induce high titres of neutralizing antibodies, Dr. Schiller said.
Despite the promising results, several questions about HPV vaccination remain unresolved, including effects on current cancer screening programs, public acceptance, price, and distribution to underserved populations.
“Women might think that they are protected from cervical cancer because they have the vaccine, and abandon their screening programs, which would be a disaster,” Dr. Schiller said. Vaccination would not replace the need for a pap test, he emphasized, although it might reduce the incidence of repeat pap tests resulting from unclear results.
Vaccine acceptance is another issue, but preliminary surveys of parents suggest that as many as 75% would agree to vaccination of their adolescent daughters. But the logistics of delivering three intramuscular doses of vaccine to early adolescent girls over a 6-month period may prove challenging, Dr. Schiller added.
The price of the vaccine is critical to how many women and girls receive it. It is likely to be expensive at first, “perhaps as much as $100 per dose,” Dr. Schiller said.
Price is a huge barrier to providing the HPV vaccine to the underserved women who need it most. “Cervical cancer is a disease of poverty—80% of cases occur in developing countries where women don't have access to good quality pap screening,” Dr. Schiller noted. “This vaccine will not have the impact it should if the only women who are vaccinated are those who already get good cervical cancer screening.”
Regional production might be the best way to build up the amount of the vaccine and reduce the cost. In addition, researchers continue to investigate a second-generation vaccine that could be administered orally.