This is the current release of the guideline.

• Human papillomavirus (HPV) infection
• Sequelae to HPV infection, such as cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts

Prevention

Family Practice
Infectious Diseases
Obstetrics and Gynecology
Pediatrics
Preventive Medicine

Advanced Practice Nurses
Health Care Providers
Nurses
Physician Assistants
Physicians
Public Health Departments

To present recommendations on the use of quadrivalent human papillomavirus (HPV) vaccine

Females aged 9 to 26 years in the United States

Quadrivalent human papillomavirus (HPV) vaccine

• Efficacy of vaccine in preventing persistent human papillomavirus (HPV) infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV
• Immunogenicity
• Safety and adverse effects
• Cost effectiveness

Searches of Electronic Databases
Searches of Unpublished Data

Not stated

Not stated

Not stated

Not applicable

Review

Not stated

Expert Consensus

The Advisory Committee on Immunization Practices (ACIP) human papillomavirus (HPV) vaccine workgroup first met in February 2004 to begin reviewing data related to the quadrivalent HPV vaccine. The workgroup held monthly teleconferences and meetings three times a year to review published and unpublished data from the HPV vaccine clinical trials, including data on safety, immunogenicity, and efficacy. Data on epidemiology and natural history of HPV, vaccine acceptability, and sexual behavior in the United States also were reviewed. Several economic and cost effectiveness analyses were considered. Presentations on these topics were made to ACIP during meetings in June 2005, October 2005, and February 2006. Recommendation options were developed and discussed by the ACIP HPV vaccine workgroup. When evidence was lacking, the recommendations incorporated expert opinion of the workgroup members. Options being considered by the workgroup were presented to ACIP in February 2006. The final recommendations were presented to ACIP at the June 2006 ACIP meeting. After discussions, minor modifications were made and the recommendations were approved at the June 2006 meeting. Modifications were made to the ACIP statement during the subsequent review process at CDC to update and clarify wording in the document.

Not applicable

Cost Effectiveness of HPV Vaccine

Since 2003, four studies have estimated the potential cost effectiveness of human papillomavirus (HPV) vaccination in the context of cervical cancer screening practices in the United States. Two of these studies applied Markov models to estimate the cost per quality-adjusted life year (QALY), focusing on the costs and impact of HPV vaccination for a given cohort, without considering the effect of vaccination on HPV transmission in the population (herd immunity). The other studies applied dynamic transmission models to incorporate the benefits of herd immunity in estimating the cost effectiveness of HPV vaccination.

The two studies based on Markov models of the natural history of HPV infection examined the cost effectiveness of vaccinating females aged 12 years. One study assumed 100% vaccine coverage, 90% vaccine efficacy against HPV 16/18, lifetime duration of protection, and a cost of $377 per vaccine series. Under these assumptions, an estimated 58% reduction was achieved in the lifetime risk for cervical cancer for the vaccinated cohort at a cost of $24,300 (2002 dollars) per QALY compared with no vaccination. A second study assumed 70% vaccine coverage, 75% efficacy against all high-risk HPV types, 10 years duration of protection plus 10 additional years of protection with a booster, and a cost of $300 per vaccine series plus $100 per booster. Under these assumptions, an estimated 20% reduction in cervical cancer incidence was achieved in the vaccinated cohort at a cost of $22,800 per QALY (2001 dollars) compared with no vaccination.

The two cost effectiveness analyses based on dynamic transmission models examined the cost effectiveness of vaccinating females. One study assumed vaccination at age 12 years with 70% vaccine coverage. The vaccine cost $300 per series plus $100 per booster and targeted HPV 16/18 with 90% efficacy and 10-year duration of protection plus 10 additional years with a booster. Under these assumptions, the lifetime risk for cervical cancer among vaccinated females would be reduced by 62% at a cost per QALY of $14,600 (2001 dollars) compared with no vaccination. A second study assumed vaccination at or before age 12 years with 70% vaccine coverage. The vaccine cost $360 per series and targeted HPV types 6, 11, 16, and 18, with 90% efficacy against infection and 100% efficacy against HPV-related diseases attributable to these HPV types, with lifelong duration of protection. Under these assumptions, over the long term, a reduction of approximately 75% was achieved in the cervical cancer incidence rate attributable to HPV 16 and 18 at a cost of $3,000 per QALY in 2005 dollars compared with no vaccination. This model also suggested that a catch-up program for females aged 12 to 24 years would cost $4,700 per QALY compared with vaccination of females aged 12 years only.

The cost per QALY gained by routine vaccination of females at age 12 years in the published studies ranged from $3,000 to $24,300. The results summarized are calculated using base-case scenarios, which vary across studies. In the sensitivity analyses, when base-case assumptions were modified, the estimated cost effectiveness ratios changed substantially. For example, factors such as duration of vaccine-induced protection, duration of natural immunity, frequency of cervical cancer screening, vaccine coverage, and vaccine cost impacted the estimated cost effectiveness of HPV vaccination.

Peer Review

After discussion, minor modifications were made and the recommendations were approved at the June 2006 Advisory Committee on Immunization Practices (ACIP) meeting. Modifications were made to the ACIP statement during the subsequent review process at the Centers for Disease Prevention and Control (CDC) to update and clarify wording in the document.

None provided

The type of evidence supporting the recommendations is not specifically stated.

Clinical trials indicate that the vaccine has high efficacy in preventing persistent human papillomavirus (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 females who have not already been infected with the respective HPV type.

Adverse Events

Adverse events of human papillomavirus (HPV) vaccine

• Injection site adverse events, such as pain, swelling, or erythema
• Mild to moderate systemic adverse events (see Table 9 in the original guideline document)
• Serious adverse events, including bronchospasm, gastroenteritis, headache/hypertension, vaginal hemorrhage, and injection site pain/movement impairment) in less than 0.1% of persons in all safety studies

Precautions: Preventing Syncope After Vaccination

Syncope (i.e., vasovagal or vasodepressor reaction) can occur after vaccination, most commonly among adolescents and young adults). Among reports to Vaccine Adverse Event Reporting System (VAERS) for any vaccine that were coded as syncope during 1990 to 2004, a total of 35% of these episodes were reported among persons aged 10 to 18 years. Through January 2007, the second most common report to VAERS following receipt of HPV vaccine was syncope. Vaccine providers should consider observing patients for 15 minutes after they receive HPV vaccine.

Acute Illnesses

Quadrivalent human papillomavirus (HPV) vaccine can be administered to persons with minor acute illnesses (e.g., diarrhea or mild upper respiratory tract infections with or without fever). Vaccination of persons with moderate or severe acute illnesses should be deferred until after the patient improves.

Hypersensitivity or Allergy to Vaccine Components

Quadrivalent HPV vaccine is contraindicated for persons with a history of immediate hypersensitivity to yeast or to any vaccine component. Data from passive surveillance in Vaccine Adverse Event Reporting System (VAERS) indicates that recombinant yeast derived vaccines pose a minimal risk for anaphylactic reactions in persons with a history of allergic reactions to Saccharomyces cerevisiae (baker's yeast).

The quadrivalent human papillomavirus (HPV) vaccine is a new vaccine; additional data will be available in the near future from clinical trials. These data and any new information on epidemiology of HPV will be reviewed by the Advisory Committee on Immunization Practices (ACIP), and recommendations will be updated as needed.

An implementation strategy was not provided.

Staying Healthy

Effectiveness

Not applicable: The guideline was not adapted from another source.

2007 Mar 23

Centers for Disease Control and Prevention - Federal Government Agency [U.S.]

United States Government

Advisory Committee on Immunization Practices

Human Papillomavirus Vaccine Working Group

Advisory Committee on Immunization Practices

Chairman: Jon Abramson, MD, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Executive Secretary: Larry Pickering, MD, CDC, Atlanta, Georgia

Members: Ban Mishu Allos, MD, Vanderbilt University School of Medicine, Nashville, Tennessee; Judith Campbell, MD, Baylor College of Medicine, Houston, Texas; Robert Beck, JD, Consumer Representative, Palmyra, Virginia; Reginald Finger, MD, Focus on the Family, Colorado Springs, Colorado; Janet Gilsdorf, MD, University of Michigan, Ann Arbor, Michigan; Harry Hull, MD, Minnesota Department of Health, St. Paul, Minnesota; Tracy Lieu, MD, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts; Edgar Marcuse, MD, Children's Hospital and Regional Medical Center, Seattle, Washington; Dale Morse, MD, New York State Department of Health, Albany, New York; Julia Morita, MD, Chicago Department of Public Health, Chicago, Illinois; Gregory Poland, MD, Mayo Medical School, Rochester, Minnesota; Patricia Stinchfield, MSN, Children's Hospitals and Clinics of Minnesota, St. Paul, Minnesota; John J. Treanor, MD, University of Rochester, Rochester, New York; Robin Womeodu, MD, University Hospital, Memphis, Tennessee

Ex-Officio Members: James E. Cheek, MD, Indian Health Services, Albuquerque, New Mexico; Wayne Hachey, DO, Department of Defense, Falls Church, Virginia; Geoffrey S. Evans, MD, Health Resources and Services Administration, Rockville, Maryland; Bruce Gellin, MD, National Vaccine Program Office, Washington, DC; Linda Murphy, Centers for Medicare and Medicaid Services, Baltimore, Maryland; George T. Curlin, MD, National Institutes of Health, Bethesda, Maryland; Kristin Lee Nichol, MD, Department of Veterans Affairs, Minneapolis, Minnesota

Liaison Representatives: American Academy of Family Physicians, Jonathan Temte, MD, Madison, Wisconsin, and Doug Campos-Outcalt, MD, Phoenix, Arizona; American Academy of Pediatrics, Keith Powell, MD, Akron, Ohio, and Carol Baker, MD, Houston, Texas; America's Health Insurance Plans, Andrea Gelzer, MD, Hartford, Connecticut; American College Health Association, James C. Turner, MD, Charlottesville, Virginia; American College of Obstetricians and Gynecologists, Stanley Gall, MD, Louisville, Kentucky; American College of Physicians, Kathleen M. Neuzil, MD, Seattle, Washington; American Medical Association, Litjen Tan, PhD, Chicago, Illinois; American Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; Association of Teachers of Preventive Medicine, W. Paul McKinney, MD, Louisville, Kentucky; Biotechnology Industry Organization, Clement Lewin, PhD, Cambridge, Massachusetts; Canadian National Advisory Committee on Immunization, Monica Naus, MD, Vancouver, British Columbia; Healthcare Infection Control Practices Advisory Committee, Steve Gordon, MD, Cleveland, Ohio; Infectious Diseases Society of America, Samuel L. Katz, MD, Durham, North Carolina; London Department of Health, David Salisbury, MD, London, United Kingdom; National Association of County and City Health Officials, Nancy Bennett, MD, Rochester, New York, and Jeffrey S. Duchin, MD, Seattle, Washington; National Coalition for Adult Immunization, David A. Neumann, PhD, Alexandria, Virginia; National Foundation for Infectious Diseases, William Schaffner, MD, Nashville, Tennessee; National Immunization Council and Child Health Program, Romeo S. Rodriquez, Mexico City, Mexico; National Medical Association, Patricia Whitley-Williams, MD, New Brunswick, New Jersey; National Vaccine Advisory Committee, Gary Freed, MD, Swiftwater, Pennsylvania, and Peter Paradiso, PhD, Collegeville, Pennsylvania; Society for Adolescent Medicine, Amy B. Middleman, MD, Houston, Texas; Pharmaceutical Research and Manufacturers of America, Damian A. Araga, Swiftwater, Pennsylvania

Human Papillomavirus Vaccine Working Group

Chair: Janet Gilsdorf, MD, Ann Arbor, Michigan

Members: Robert L. Beck, JD, Palmyra, Virginia; Stuart Berman, MD, Atlanta, Georgia; Joseph Bocchini, MD, Shreveport, Louisiana; Harrell Chesson, PhD, Atlanta, Georgia; Carolyn Deal, PhD, Bethesda, Maryland; Shelley Deeks, MD, Toronto, Canada; John Douglas, MD, Atlanta, Georgia; Eileen F. Dunne, MD, Atlanta, Georgia; Dan Fishbein, MD, Atlanta, Georgia; Stanley Gall, MD, Louisville, Kentucky; Bruce Gellin, MD, Washington, DC; Karen Goldenthal, MD, Rockville, Maryland; Harry Hull, MD, St. Paul, Minnesota; Samuel Katz, MD, Durham, North Carolina; Katrin Kohn, MD; Herschel W. Lawson, MD, Atlanta, Georgia; Nicole Liddon, PhD, Atlanta, Georgia; Lauri E. Markowitz, MD, Atlanta, Georgia; Eric Mast, MD, Atlanta, Georgia; Alison Mawle, PhD, Atlanta, Georgia; Amy Middleman, MD, Houston, Texas; Siobhan O'Connor, MD, Atlanta, Georgia; Mona Saraiya, MD, Atlanta, Georgia; Debbie Saslow, PhD, Atlanta, Georgia; Jane Seward, MBBS, Atlanta, Georgia; Jonathan L. Temte, MD, Madison, Wisconsin; James Turner, MD, Charlottesville, Virginia; Elizabeth R. Unger, MD, Atlanta, Georgia; Gregory S. Wallace, MD, Atlanta, Georgia; Robin Womeodu, MD, Memphis, Tennessee; Richard Zimmerman, MD, Pittsburgh, Pennsylvania; and Jane Zucker, MD, New York, New York

Centers for Disease Control and Prevention (CDC), our planners, and our content experts wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters. On behalf of CDC, Dr. Elizabeth Unger is involved in a material transfer agreement with Merck Research Laboratories to implement the competitive Luminex assay for HPV 6, 11, 16, and 18 serology. Presentations will not include any discussion of the unlabeled use of a product or a product under investigational use.

This is the current release of the guideline.

None available

This NGC summary was completed by ECRI on April 19, 2007.

No copyright restrictions apply.