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Volume 5, No. 4, April 2007
Abstract of the Month
Quadrivalent Human Papillomavirus Vaccine: Final ACIP Recommendations, CDC
Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, causing an estimated 6.2 million new infections every year. Persistent genital HPV infection can cause cervical cancer in women.
In June 2006, the quadrivalent HPV vaccine types 6,11,16,18, under the trade name GARDASIL™ (manufactured by Merck and Co.), was licensed for use among females aged 9--26 years for prevention of HPV-type–related cervical cancer, cervical cancer precursors, vaginal and vulvar cancer precursors, and anogenital warts. This report presents recommendations by the Advisory Committee on Immunization Practices (ACIP) on the use of the HPV vaccine.
Recommendations for Routine Use and Catch-Up
Routine Vaccination of Females Aged 11--12 Years
ACIP recommends routine vaccination of females aged 11--12 years with 3 doses of quadrivalent HPV vaccine. The vaccination series can be started as young as age 9 years.
Catch-Up Vaccination of Females Aged 13--26 Years
Vaccination also is recommended for females aged 13--26 years who have not been previously vaccinated or who have not completed the full series. Ideally, vaccine should be administered before potential exposure to HPV through sexual contact; however, 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 would receive full benefit from vaccination. Vaccination would provide 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. Pap testing and screening for HPV DNA or HPV antibody are not needed before vaccination at any age.
Dosage and Administration
The vaccine should be shaken well before administration. The dose of quadrivalent HPV vaccine is 0.5 mL, administered intramuscularly (IM), preferably in the deltoid muscle.
Recommended Schedule
Quadrivalent HPV vaccine is administered in a 3-dose schedule. The second and third doses should be administered 2 and 6 months after the first dose.
Minimum Dosing Intervals and Management of Persons Who Were Incorrectly Vaccinated
The minimum interval between the first and second doses of vaccine is 4 weeks. The minimum recommended interval between the second and third doses of vaccine is 12 weeks. Inadequate doses of quadrivalent HPV vaccine or vaccine doses received after a shorter-than-recommended dosing interval should be readministered.
Interrupted Vaccine Schedules
If the quadrivalent HPV vaccine schedule is interrupted, the vaccine series does not need to be restarted. If the series is interrupted after the first dose, the second dose should be administered as soon as possible, and the second and third doses should be separated by an interval of at least 12 weeks. If only the third dose is delayed, it should be administered as soon as possible.
Simultaneous Administration with Other Vaccines
Although no data exist on administration of quadrivalent HPV vaccine with vaccines other than hepatitis B vaccine, 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.
Cervical Cancer Screening Among Vaccinated Females
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.
Groups for Which Vaccine is Not Licensed
Vaccination of Females Aged <9 Years and >26 Years
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 under way among children aged <9 years.
Vaccination of Males
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 on efficacy in males at any age. Efficacy studies in males are under way.
Special Situations Among Females Aged 9--26 Years
Equivocal or Abnormal Pap Test or Known HPV Infection
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.
Genital Warts
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.
Lactating Women
Lactating women can receive HPV vaccine.
Immunocompromised Persons
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.
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).
Precautions and Contraindications
Acute Illnesses
Quadrivalent 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 recombinent yeast derived vaccines pose a minimal risk for anaphylaxic reactions in persons with a history of allergic reactions to Saccharomyces cerevisiae (baker's yeast).
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 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.
MMWR March 12, 2007 / 56(Early Release);1-24
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr56e312a1.htm
Editorial comment: Amy Groom, Steve Holve, and Ros Singleton
Strategy for a Successful HPV Vaccine Rollout in Indian Country
The Advisory Committee on Immunization Practices (ACIP) recommends that the human papillomavirus (HPV) vaccine be routinely administered to females 11 – 12 years of age, with catch up vaccination for women 13 – 26 years. The full recommendation can be found at the link below. This vaccine is available at no charge through the Vaccines for Children program for all VFC-eligible women 9 – 18 years, per the VFC resolution, link below.
The quadrivalent HPV vaccine is remarkably effective. In studies, the vaccine was 100% effective in preventing carcinoma in situ (CIN) 2/3 from 16/18 which are associated with 70% of cervical cancer, but this success comes at a cost. In the private sector, the vaccine costs $120 per dose or $360/person for a complete series of three vaccinations. IHS and tribal sites that are eligible and order through the VA Pharmaceutical Prime Vendor (PPV) can get the vaccine at $84.17/dose.
While the quadrivalent HPV vaccine was placed on the CDC federal contract in October of 2005, and is currently available through VFC in most states, some states have been delayed in the roll out of the vaccine or have had to restrict access to the vaccine to certain age groups due to limitations in VFC and state funds. Eventually coverage with HPV vaccine for all VFC eligible female patients 9 – 18 years of age should be available.
IHS recommends implementation of the full ACIP recommendation, targeting females 11 – 12 year olds with routine vaccination, and catch up vaccination for 13 – 18 or 13-26 year olds where possible. In states where HPV vaccine is not yet available for 11 – 18 year olds due to limits in supply and/or funding, IHS recommends the following:
1. Target girls 11-12 years old and 17-18 years old with HPV vaccine starting this summer and fall. This will capture older girls who will lose their VFC eligibility if we don't try to immunize them this year.
2. Ensure that each state has reliable numbers of the IHS female user population 9 – 18 years of age. This may assist states in lobbying the CDC for additional funds for HPV vaccine which should ultimately allow for full implementation of the ACIP recommendation for VFC-eligible patients seen by IHS and tribal facilities.
3. If a state is unable or unwilling to provide vaccine to at least the 11 -1 2 year olds and 17 – 18 year olds, than consideration should be given for the agency to approach the CDC about increasing funding to ensure that AI/AN girls receive the HPV vaccine to which they are entitled by statute.
In order to vaccinate women 19 – 26 years old, the following strategies may help to offset the cost:
Medicaid - If Medicaid covers HPV vaccine for this age group in your state, contact your billing department to see how to bill for this vaccine. If you have a single fee for Medicaid visits, you may be able to schedule vaccinations with a billable provider (e.g. physician, nurse practitioner, physician assistant or midwife; not a nurse only visit) which may allow clinics to recover the cost of this immunization. The Alaska Native Medical Center (ANMC) in Anchorage has come up with a method to bill Medicaid by writing a prescription for HPV vaccine so that it can be billed separate from the clinic visit.
Merck Vaccine Patient Assistance Program (PAP) - The Merck PAP allows patients over age 19 years who meet certain income and insurance coverage criteria to obtain HPV vaccine for free. Sites purchase some vaccine up front, and for patients who are approved by the Merck program, the vaccine is replaced by Merck to the dispensing pharmacy on a quarterly basis. The applicant must apply from a facility that is not ‘wholly owned and operated by the government’. Hence, all tribal and urban facilities would qualify, plus those IHS facilities that receive additional funding, other than federal funding, e. g., grants, contracts, private funding, etc. If you are in doubt whether your facility qualifies, please contact (800) 293-3881 toll free 8:00 AM–8:00 PM EST Monday – Friday. If your facility does not qualify, then the patient could apply from a different facility, e. g., private, or semi-governmental clinic.
The application process is straightforward. Sites usually hear within the hour if the application is approved, though it can take up to 4 hours. The application is available at the link below.
See also the STD Corner below which has other Frequently Asked Questions on HPV vaccine.
Resources:
CDC Recommendations
http://www.cdc.gov/nip/recs/provisional_recs/hpv.pdf
Vaccines
For Children Resolution
http://www.cdc.gov/nip/vfc/acip_resolutions/0606hpv.pdf
Merck Vaccine Patient Assistance Program Home
http://www.merck.com/merckhelps/vaccines/home.html
Merck Vaccine Patient Assistance Program Application
http://www.merck.com/merckhelps/vaccines/mvpap_app.pdf
Human papillomavirus vaccination. ACOG Committee Opinion No. 344. American College of Obstetricians and Gynecologists. Obstet Gynecol 2006;108:699–705.
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OB/GYN
Dr. Neil Murphy is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Murphy is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to Native or indigenous peoples around the world. Please don't hesitate to contact him by e-mail or phone at 907-729-3154.
