ACIP outlines plan for Gardasil vaccine

The quadrivalent human papil-lomavirus vaccine should be given to all girls at age 11-12, and to all female 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. Merck’s Gardasil vaccine, licensed in early June, is now available. The three-dose series, given over a 6-month period, is indicated for the prevention of disease caused by HPV types 16 and 18, which are associated with about 70% of cervical cancers, as well as types 16 and 18, both associated with genital warts. 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. The CDC is not obligated to follow ACIP’s advice, but it usually does. Although the vaccine should be administered prior to the initiation of sexual activity, females who are already sexually active should still be vaccinated. Use of the vaccine in young women has been strongly endorsed by the American College of Physicians, ACP liaison were thrilled that the recommendation includes young adult women. They’re currently working on education efforts. 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.

Serology and PCR testing done by Merck showed that among females aged 16-26 years, 76% were still naïve to all four HPV types in the vaccine, and less than 1% had evidences of past or present infection with all four types. Among those infected with one, two, or three 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. 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. These patients should be told that they may be already infected with one or more vaccines 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. But administration should be delayed among women with moderate or severe acute illness; women with a history of immediate hypersensitivity or severe allergic reaction to yeast or any vaccine component should not receive it. 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.

But 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. The recommendations for universal immunization of females through the entire age range approved by the FDA – as opposed to a "permissive" recommendation outside of the 11-12 year "adolescent visit" age – is exactly what the American College of Obstetricians and Gynecologists wanted. There are between 2 and 3 million abnormal PAP smears a year in the United States, due largely to HPV. If we can eliminate these, it will be a huge leap forward. This vaccine is the biggest thing in women’s health since the pill. Whether a booster will be required is yet to be determined, but new data presented by Merck Research Laboratories suggest that the vaccine remains effective for at least 5 years. Of 468 subjects followed to 60 months, HPV-related infection developed in less than 1% of the 235 Gardasil recipients, compared with 2% 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 have thousands-fold greater increased 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. He also presented new safety data for 6,160 vaccine recipients and 4,064 controls. Fever of 100 degrees or greater was more common among the vaccine subjects (11.4% vs. 9.6%), but the proportion with fever of 102 degrees or higher was only slightly higher with the vaccine (1.5% vs. 1.0%). Pregnancies occurred in about 1,100 women in each group, of which about 60% in each produced live births. Fetal loss occurred in 38% of the vaccine recipients and in 16 placebo infants. None of the anomalies were considered likely to be due to the vaccine. Both Merck and the CDC plan to conduct postmarketing safety surveillance of the vaccine. The company will monitor for exposure during pregnancy, for increased infection rates for HPV types other than those included in the vaccine, and for detection of unanticipated safety signals. The CDC, along with the Food and Drug Administration, will be following Gardasil with the passive Vaccine Adverse Event Reporting System. Also, vaccine recipients will be among those monitored in "real time" by the CDC and a group of eight large managed care organizations that make up the Vaccine Safety Datalink. ACIP also voted to include Gardasil in the federally funded Vaccines for Children program. The vaccine will cost $360 for the three-dose series ($120/dose) in the private sector; the public contract price has not yet been determined. Although Gardasil will be costly, an analysis presented by CDC economist, suggest 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, currently given routinely to infants and adolescents, respectively.