# Indian Child Health Notes

**April 2007**

# 

# [HPV Vaccine: Newest ACIP Recommendations - Comments by Amy Groom](http://www.ihs.gov/MedicalPrograms/MCH/M/obgyn0407_AOM.cfm)

# *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

#### [Editorial comment:]{.underline} 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:**

**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.