ATLANTA — The quadrivalent human papillomavirus vaccine should be given to all girls at age 11–12, and to all females aged 13–26 who have not been previously vaccinated, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices voted at its June meeting.
The committee also voted to include the vaccine, Merck's Gardasil, into the federally funded Vaccines for Children program. The vaccine will cost $360 for the three-dose series ($120 per dose) in the private sector; the public contract price has not yet been determined.
The CDC is not obligated to follow the committee's advice, but it usually does.
Gardasil was licensed by the Food and Drug Administration in early June and is available now. Its three-dose series, designed to be given over 6 months, is indicated for the prevention of disease caused by HPV types 16 and 18, which are associated with about 70% of cervical cancer, as well as types 6 and 11, both associated with genital warts. However, the decision to vaccinate should not be based on Pap testing, HPV DNA testing, or HPV serologic testing, and no changes are recommended in current guidelines for cervical cancer screening, ACIP said.
Although the vaccine should be administered prior to the initiation of sexual activity, females who are already sexually active should still be vaccinated. The vaccine can also be given to girls as young as 9 years of age, at the provider's discretion.
The American Academy of Family Physicians will in all likelihood endorse ACIP's recommendations, Dr. Jonathan Temte, AAFP liaison, said in an interview. “I don't anticipate any conflicts.”
This vaccine fits right into the practice of family medicine, he noted. “The endorsement covers children, adolescents, and young adults, our bread-and-butter patients. It really embraces the preventive care which we FPs are big believers in,” said Dr. Temte of the University of Wisconsin, Madison.
Dr. Lauri Markowitz of the CDC's National Center for HIV, STD, and TB Prevention provided background data and guided the ACIP through a series of votes on the use of the vaccine. A national survey conducted in 2002 found that 26% of girls in the United States have had vaginal sex by age 15; the figure rises to 77% by age 19. Once sexual activity begins, the incidence of HPV infection rises to 40% within 2 years and to more than 50% within 4 years, she said.
However, serology and PCR testing done by Merck showed that among females aged 16–26 years, 76% were still naive to all four of the HPV types in the vaccine and less than 1% had evidence of past or present infection with all four types. Therefore, among those infected with 1, 2, or 3 HPV vaccine types, the vaccine would still be expected to protect against disease caused by the other types.
“Although overall vaccine effectiveness would be lower, most females will still derive benefit from vaccination,” Dr. Markowitz said.
In a separate vote, ACIP also recommended vaccination for women with an equivocal or abnormal Pap test, those who have tested positive for HPV infection using the Hybrid Capture II, and for those with genital warts. However, these patients should be told that they may be already infected with one or more vaccine HPV types and that data do not indicate that the vaccine will have a therapeutic effect on existing cervical lesions, warts, or HPV infection.
Women who are lactating and those who are immunosuppressed can receive the vaccine, which is not made from live virus. However, administration should be delayed among women with moderate or severe acute illness, and those with a history of immediate hypersensitivity or severe allergic reaction to yeast or any vaccine component should not receive it, ACIP recommended.
Administration of the vaccine should be delayed until after completion of a known pregnancy. If a pregnancy is revealed after a woman has received one or two doses, the rest of the series should be postponed until after the pregnancy.
However, there is no need to test women for pregnancy prior to initiating the vaccine series, and no intervention is indicated if the vaccine is given to a pregnant woman. In fact, Gardasil is the first vaccine ever to receive a category B designation, based on animal and human data indicating no causal association with adverse outcomes of pregnancy or adverse events to the developing fetus, Dr. Markowitz noted.
Whether a booster will be required is yet to be determined, but new data presented by Dr. Eliav Barr, of Merck Research Laboratories, suggest that the vaccine remains effective for at least 5 years. Of a total 468 subjects followed to 60 months, HPV-related infection developed in 0.85% of the 235 Gardasil recipients, compared with 2.0% of the 233 placebo subjects.
Should waning immunity develop beyond 5 years, data from a subset of 114 Gardasil subjects and 127 controls who were given one dose of Gardasil at 60 months suggest that a single-dose booster would likely work: The original Gardasil recipients demonstrated thousands-fold greater increases in anti-HPV geometric mean titers for both types 16 and 18 than did those who had received placebo 5 years earlier, suggesting that the vaccine induces strong immune memory.
“These data are very promising in terms of long-term efficacy,” Dr. Barr said.
Dr. Barr also presented new safety data for 6,160 vaccine recipients and 4,064 controls. Fever of 100° or greater was more common among the vaccine subjects (11.4% vs. 9.6%), but the proportion with fever of 102° or higher was slightly higher with the vaccine (1.5% vs. 1.0%).
Pregnancies occurred in approximately 1,100 women in each group, of which about 60% in each produced live births. Fetal loss occurred in 38% of the vaccine subjects and in 40% of placebo recipients. Congenital anomalies occurred in 10 infants of vaccine recipients and in 16 placebo infants. None of the anomalies were considered likely to be due to the vaccine, Dr. Barr said.
Both Merck and the CDC plan to conduct postmarketing safety surveillance of the vaccine. The company will monitor for exposure during pregnancy, for replacement with non-vaccine types, and for detection of unanticipated safety signals, Dr. Adrian Dana, of Merck, told ACIP.
The CDC, along with the FDA, also will be following Gardasil post licensure with the passive Vaccine Adverse Event Reporting System. In addition, vaccine recipients will be among those monitored in “real time” by the CDC and a group of eight large managed care organization that make up the Vaccine Safety Datalink, the CDC's Dr. John Iskander said.
Although Gardasil will be costly, an analysis presented by CDC economist Harrell Chesson, Ph.D., suggests that it will likely be cost saving in terms of cost per life-year saved, similar to the hepatitis B, DTaP, and varicella vaccines, and far more cost-effective than the pneumococcal and meningococcal conjugate vaccines.
Given the extensive media coverage of this vaccine, Dr. Temte anticipates an unprecedented patient demand. But at the same time, getting everyone scheduled for all three doses will be a challenge.
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