Advisory Committee on Immunization Practices Issues Guidelines for Gardasil, HPV Vaccine

Special Report

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Source. CDC. Human Papillomavirus Vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2007; 56:1-24.

The Advisory Committee on Immunization Practices (ACIP) has finally published its recommendations for the use of Gardasil, the quadrivalent human papillomavirus vaccine that has recently become available. While the essence of these recommendations has been known for some months, their publication is important in that some third party payers resist reimbursement for the vaccine until they appear in print as an official document. The following is a summary of those recommendations.

Who should receive the vaccine?

Routine vaccination is recommended for females at 11-12 years of age, but the 3 dose series may be initiated as early as age 9 years.

What about females older than 12 years of age?

Vaccination is also recommended for females aged 13-26 years who have not been previously vaccinated or who have not completed the full series.

What about females younger that 9 years or older than 26 years of age?

The quadrivalent HPV vaccine is not licensed for use among females aged < 9 years or those aged > 26 years. Studies are ongoing among females aged > 26 years. No studies are underway in women greater than 26 years of age.

What about females who are already sexually active?

While it is preferable that the vaccine be administered before potential exposure to HPV through sexual contact, females who might have already been exposed to HPV should be vaccinated. Sexually active females who have not been infected with any of the HPV vaccine types receive full benefit from vaccination while vaccination provides less benefit to females if they have already been infected with one or more of the four vaccine HPV types. However, 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.

Is testing required before vaccine administration?

Pap testing and screening for HPV DNA or HPV antibody are not needed before vaccination at any age.

Should females with an equivocal or abnormal Pap test or who are known to have HPV infected be vaccinated?

Females who have an equivocal or abnormal Pap test could be infected with any of approximately 40 high-risk or low-risk genital HPV types. Such females are unlikely to be infected with all four HPV vaccine types, and they might not be infected with any HPV vaccine type. Vaccination would provide protection against infection with HPV vaccine types not already acquired. With increasing severity of Pap test findings, the likelihood of infection with HPV 16 or 18 increases and the benefit of vaccination would decrease. Women should be advised that results from clinical trials do not indicate the vaccine will have any therapeutic effect on existing HPV infection or cervical lesions.

Females who have a positive HC2 High-Risk test conducted in conjunction with a Pap test could have infection with any of 13 high-risk types. This assay does not identify specific HPV types, and testing for specific HPV types is not conducted routinely in clinical practice. Women with a positive HC2 High-Risk test might not have been infected with any of the four HPV vaccine types. Vaccination would provide protection against infection with HPV vaccine types not already acquired. However, women should be advised that results from clinical trials do not indicate the vaccine will have any therapeutic effect on existing HPV infection or cervical lesions.

Does the presence or history of genital warts obviate the need for vaccination?

A history of genital warts or clinically evident genital warts indicates infection with HPV, most often type 6 or 11. However, these females might not have infection with both HPV 6 and 11 or infection with HPV 16 or 18. Vaccination would provide protection against infection with HPV vaccine types not already acquired. However, females should be advised that results from clinical trials do not indicate the vaccine will have any therapeutic effect on existing HPV infection or genital warts.

Can a woman who is lactating receive the vaccine?

Yes.

What about vaccination during pregnancy?

Quadrivalent HPV vaccine is not recommended for use in pregnancy. The vaccine has not been causally associated with adverse outcomes of pregnancy or adverse events in the developing fetus. However, data on vaccination during pregnancy are limited. Until additional information is available, initiation of the vaccine series should be delayed until after completion of the pregnancy. If a woman is found to be pregnant after initiating the vaccination series, the remainder of the 3-dose regimen should be delayed until after completion of the pregnancy. If a vaccine dose has been administered during pregnancy, no intervention is needed. A vaccine in pregnancy registry has been established; patients and health-care providers should report any exposure to quadrivalent HPV vaccine during pregnancy (telephone: (800) 986-8999)).

Can immunocompromised patients receive the vaccine?

Because quadrivalent HPV vaccine is a noninfectious vaccine, it can be administered to females who are immunosuppressed as a result of disease or medications. However, the immune response and vaccine efficacy might be less than that in persons who are immunocompetent.

Can the vaccine be administered to someone suffering from an acute illness?

Quadrivalent HPV vaccine can be administered to persons with minor acute illnesses (eg, 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.

What about allergies?

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 anaphylaxic reactions in persons with a history of allergic reactions to Saccharomyces cerevisiae (baker's yeast).

What is the dose, route of administration and schedule for the vaccine?

The dose of the quadrivalent vaccine is 0.5 mL (shake well before administration) given intramuscularly, preferably in the deltoid muscle. The minimum recommended interval between the first and second doses is 4 weeks. The second and third doses should be administered 2 and 6 months after the first dose. The minimum interval between these two doses should at 12 weeks. The third dose, if delayed beyond the recommended time, should be administered as soon as possible.

Can it be administered together with other vaccines?

The quadrivalent HPV vaccine is not a live vaccine and has no components that adversely impact safety or efficacy of other vaccinations. Quadrivalent HPV vaccine can be administered at the same visit as other age appropriate vaccines, such as the Tdap and quadrivalent meningococcal conjugate (MCV4) vaccines. Administering all indicated vaccines together at a single visit increases the likelihood that adolescents and young adults will receive each of the vaccines on schedule. Each vaccine should be administered using a separate syringe at a different anatomic site.

If someone has been vaccinated, do they need to continue cervical cancer screening?

Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. HPV types in the vaccine are responsible for approximately 70% of cervical cancers; females who are vaccinated could subsequently be infected with a carcinogenic HPV type for which the quadrivalent vaccine does not provide protection. Furthermore, those who were sexually active before vaccination could have been infected with a vaccine type HPV before vaccination. Health-care providers administering quadrivalent HPV vaccine should educate women about the importance of cervical cancer screening.

Should males be vaccinated?

Quadrivalent HPV vaccine is not licensed for use among males. Although data on immunogenicity and safety are available for males aged 9-15 years, no data exist regarding efficacy in males of any age, although efficacy studies are in progress.

Patients occasionally experience syncope after receiving injections, including for vaccines. Is this an issue with the quadrivalent HPV vaccine?

Syncope (ie, vasovagal or vasodepressor reaction) can occur after vaccination, most commonly among adolescents and young adults. Among reports to VAERS for any vaccine that were coded as syncope during 1990-2004, a total of 35% of these episodes were reported among persons aged 10-18 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.

If a patient suffers an adverse event after vaccine receipt, how do I report it?

As with any newly licensed vaccine, surveillance for rare adverse events associated with administration of quadrivalent HPV vaccine is important for assessing its safety in widespread use. All clinically significant adverse events should be reported to VAERS at http://vaers.hhs.gov, even if causal relation to vaccination is not certain. VAERS reporting forms and information are available electronically at www.vaers.hhs.gov or by telephone ((800) 822-7967). Web-based reporting is available and providers are encouraged to report electronically at https://secure.vaers.org/VaersDataEntryintro.htm to promote better timeliness and quality of safety data.

Safety surveillance for adolescent quadrivalent HPV vaccine, Tdap, MCV4, and other vaccines is being conducted on an ongoing basis in cooperation with FDA. A vaccine in pregnancy registry has been established by Merck and Co., Inc.; patients and health-care providers should report any exposure to quadrivalent HPV vaccine during pregnancy (telephone: ((800) 986-8999).

What is the duration of protection provided by the vaccine?

As with any new vaccine, the duration of protection is not yet known. Long-term data on duration of antibody response and clinical protection will be obtained through studies conducted in the Nordic countries through the Nordic cancer registries and through other studies in the United States. Follow up of vaccine trial participants aged 9-15 years will continue for up to 10 years after dose 3. This will include evaluation of antibody titers and, in participants who reach their 16th birthday, evaluation of vaccine effectiveness.

Won't the widespread use of this vaccine simply result in a change in HPV types causing infection?

The prevalence and incidence of HPV types in the vaccine are expected to decrease as a result of vaccination. Studies are planned to monitor HPV types in various populations and specimens.

How will the long term safety of the vaccine be monitored?

Postlicensure studies to evaluate general safety and pregnancy outcomes will be conducted by the manufacturer and independently by CDC. Monitoring will be accomplished through VAERS and CDC's Vaccine Safety Datalink, which will include surveillance of cohorts of recently vaccinated females and evaluation of outcomes of pregnancy among those pregnant at the time of vaccination. The manufacturer will be monitoring long-term safety as part of the Nordic Cancer Registry Program.