ACIP Recommends Quadrivalent HPV Vaccine

March 23, 2007 — The Advisory Committee on Immunization Practices (ACIP) recommends quadrivalent human papillomavirus (HPV) vaccine for girls and women aged 9 to 26 years, according to guidelines published in the March 12 Early Release issue of the Morbidity and Mortality Weekly Report.

"Genital HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year," write Lauri E. Markowitz, MD, from the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention (proposed), and colleagues. "Although the majority of infections cause no clinical symptoms and are self-limited, persistent infection with oncogenic types can cause cervical cancer in women.... Cervical cancer rates have decreased in the United States because of widespread use of Papanicolaou testing, which can detect precancerous lesions of the cervix before they develop into cancer; nevertheless, during 2007, an estimated 11,100 new cases will be diagnosed and approximately 3,700 women will die from cervical cancer."

The guidelines represent the first ACIP statement on the use of a quadrivalent HPV vaccine licensed by the US Food and Drug Administration on June 8, 2006. This report reviews the epidemiology of HPV and associated diseases, the licensed HPV vaccine, and recommendations for vaccination among girls and women aged 9 to 26 years in the United States.

The licensed HPV vaccine is composed of HPV L1, the major capsid protein of HPV. The quadrivalent HPV vaccine is a mixture of 4 HPV type-specific noninfectious virus-like particles prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant.

In clinical trials, the vaccine was highly effective in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among girls and women who had not already been infected with the respective HPV type. Although there is no evidence of protection against disease caused by HPV types with which girls and women are infected at the time of vaccination, girls and women infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other vaccine HPV types.

In clinical trials, systemic clinical adverse events were reported by a similar proportion of HPV vaccine and placebo recipients, and the maximum intensity rating of systemic clinical adverse events was mild or moderate. Vaccine-related serious adverse events occurred in less than 0.1% of persons, and included bronchospasm, gastroenteritis, headache/hypertension, vaginal hemorrhage, and injection site pain/movement impairment.

In the overall safety evaluation, 10 persons in the group that received quadrivalent HPV vaccine and 7 persons in the placebo group died during the course of the trials, but none of the deaths were considered to be vaccine related.

Quadrivalent HPV vaccine is not recommended for use in pregnancy.

Quadrivalent HPV vaccine is available as a sterile suspension for injection in a single-dose vial or a prefilled syringe, and it is administered intramuscularly as 3 separate 0.5-mL doses. The second dose should be administered 2 months after the first dose and the third dose 6 months after the first dose.

The recommended age for vaccination of girls is 11 to 12 years during the established young adolescent healthcare visit at age 11 to 12 years as recommended by several professional organizations when other vaccines are also recommended.

The HPV vaccine can be given as young as age 9 years, and catch-up vaccination is recommended for teens and women aged 13 to 26 years who were not previously vaccinated. It is not possible for a clinician to assess the extent to which sexually active persons would benefit from vaccination, and the risk for HPV infection might continue as long as persons are sexually active. At any age, Papanicolaou testing and screening for HPV DNA or HPV antibody are not recommended before vaccination.

The guidelines caution that vaccination is not a substitute for routine cervical cancer screening and girls and women who have received vaccination should have cervical cancer screening according to the recommended protocol.

After reviewing available data on the epidemiology and natural history of HPV, vaccine acceptability, and sexual behavior in the United States, the ACIP also considered economic and cost-effectiveness analyses presented during meetings in June 2005, October 2005, and February 2006. The ACIP HPV vaccine workgroup developed recommendation options based on the above, as well as on expert opinion of the workgroup members.

The final recommendations were presented to ACIP at the June 2006 ACIP meeting and approved at the June 2006 meeting. The guidelines also recommend long-term follow-up studies to determine duration of protection. Additional data available in the near future from clinical trials and any new information on epidemiology of HPV will be reviewed by ACIP as they become available, and recommendations will be updated as needed.

"The recommendation for routine vaccination of females aged 11 to 12 years is based on several considerations, including studies suggesting that quadrivalent HPV vaccine among adolescents will be safe and effective; high antibody titers achieved after vaccination at age 11 - 12 years; data on HPV epidemiology and age of sexual debut in the United States; and the high probability of HPV acquisition within several years of sexual debut," the authors write. "Ideally, HPV vaccine should be administered before sexual debut, and duration of protection should extend for many years, providing protection when exposure through sexual activity might occur. The vaccine has been demonstrated to provide protection for at least 5 years without evidence of waning protection."

Morbid Mortal Wkly Rep Early Release. 2007;56:1-24.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr56e312a1.htm