HPV Vaccine Recommendations, PEDIATRICS Volume 129, Number 3, March 2012.

1. Organizational Principles to Guide and Define the Child
Health Care System and/or Improve the Health of all Children
POLICY STATEMENT
HPV Vaccine Recommendations
abstract COMMITTEE ON INFECTIOUS DISEASES
KEY WORDS
On October 25, 2011, the Advisory Committee on Immunization Practices human papillomavirus, HPV, vaccine, males, females, adolescents,
immunization, cancer
of the Centers for Disease Control and Prevention recommended that
ABBREVIATIONS
the quadrivalent human papillomavirus vaccine (Gardasil; Merck & Co, AAP—American Academy of Pediatrics
Inc, Whitehouse Station, NJ) be used routinely in males. The American HPV—human papillomavirus
Academy of Pediatrics has reviewed updated data provided by the HPV2—bivalent human papillomavirus vaccine
HPV4—quadrivalent human papillomavirus vaccine
Advisory Committee on Immunization Practices on vaccine efficacy,
safety, and cost-effectiveness as well as programmatic considerations This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors
and supports this recommendation. This revised statement updates have filed conflict of interest statements with the American
recommendations for human papillomavirus immunization of both Academy of Pediatrics. Any conflicts have been resolved through
males and females. Pediatrics 2012;129:602–605 a process approved by the Board of Directors. The American
Academy of Pediatrics has neither solicited nor accepted any
commercial involvement in the development of the content of
INTRODUCTION this publication.
All policy statements from the American Academy of Pediatrics
The American Academy of Pediatrics (AAP) recommends immunization
automatically expire 5 years after publication unless reaffirmed,
against human papillomavirus (HPV) for all 11- through 12-year-old revised, or retired at or before that time.
children as part of the adolescent immunization platform. Quadriva-
lent HPV vaccine (HPV4; Gardasil; Merck & Co, Inc, Whitehouse Station, NJ)
is the only vaccine approved for males, and either HPV4 or bivalent HPV
vaccine (HPV2; Cervarix; GlaxoSmithKline, Middlesex, UK) may be used in
females. This brief policy statement supersedes the previous AAP “per-
missive recommendation” for use of HPV4 in males1 and the retired 2007
policy statement.2 A complete rationale is available in the statement from
the Advisory Committee on Immunization Practices of the Centers for
Disease Control and Prevention.3
www.pediatrics.org/cgi/doi/10.1542/peds.2011-3865
BRIEF BACKGROUND AND RATIONALE doi:10.1542/peds.2011-3865
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
HPVs are the most common sexually transmitted viruses in the United
States. The highest prevalence of HPV infection is found in sexually Copyright © 2012 by the American Academy of Pediatrics
active adolescents and young adults. Most HPV infections are asymp-
tomatic and resolve without complications within 2 years. However,
persistent infection with high-risk HPV types is responsible for most
cervical and anal cancers in females. In males, high-risk HPV types are
responsible for a large proportion of cancers of the mouth and
pharynx, which are increasing in recent years, and of anal and penile
cancers. Each year in the United States, approximately 15 000 cases of
cancer in females and 7000 cases of cancer in males are caused by
HPV types 16 and 18. Of the cancers in males, the great majority are
cancers of the oropharynx (approximately 5400), followed by anal
cancer (approximately 1400) and penile cancer (approximately 300).
The rationale for routine HPV immunization at 11 through 12 years of
age is twofold. First, optimal vaccine efficacy is derived if the vaccine is
602 FROM THE AMERICAN ACADEMY OF PEDIATRICS

2. FROM THE AMERICAN ACADEMY OF PEDIATRICS
administered before onset of sexual disproportionately affecting females 26 years of age, vaccine efficacy was
activity. The vaccine is inactive against during their reproductive years. Rubella demonstrated against genital warts
HPV types previously acquired by the vaccine (a component of the measles- caused by vaccine types. HPV4 was
vaccine recipient. Second, antibody re- mumps-rubella vaccine) is intended permitted in males in 2010. Also in 2010,
sponses are highest at ages 9 through primarily to prevent fetal miscarriages the US Food and Drug Administration
15 years. Immunization of males pro- and malformations after rubella infec- added a new indication of prevention
vides direct benefit to males, including tion during pregnancy, and hepatitis B of anal cancer in males and females on
prevention of genital warts and anal virus vaccine prevents cirrhosis of the the basis of data from an efficacy study
cancer. Prevention of oropharyngeal liver and hepatocellular carcinoma in males. In new data from a substudy
cancer has not been studied but is caused by hepatitis B virus acquired at of high-risk sexually active young men
biologically plausible. In addition, im- time of birth or through later sexual (men who have sex with men), protec-
munization of males is expected to exposure. tion has been demonstrated against
provide indirect benefit for females precancerous lesions of the anus. These
through herd immunity. Four years af- HPV VACCINES data contribute to the current rec-
ter the initial recommendation for im- ommendation. The study did not have
munization of females, uptake of the HPV4 contains no viral DNA and is not
adequate power (too few penile or
infectious. It consists of bioengineered
HPV vaccine lags behind other vaccines perineal precancerous lesions) to
viruslike particles produced from the
offered in adolescence; results of the support benefit in preventing these
major capsid protein of HPV types 16
2010 National Immunization Survey in- precancerous conditions. No studies
and 18, which are responsible for 70%
dicated 32% of females 13 through 17 of HPV4 vaccine protection against
of cases of cervical, 87% of anal, 60%
years have completed the 3-dose series. oropharyngeal cancers or recurrent
of oropharyngeal, and 31% of penile
The cost-effectiveness of male immu- respiratory papillomatosis have been
cancers. In addition, the vaccine in-
nization is sensitive to a range of as- conducted.
cludes capsid proteins of types 6 and
sumptions, such as vaccine efficacy, HPV2, directed at HPV types 16 and 18,
11, which are responsible for 90% of
vaccine coverage of females, and the was licensed for use in females in 2009.
genital warts and almost all cases of
effect of HPV-associated diseases on This vaccine is highly immunogenic,
juvenile recurrent respiratory papil-
quality of life. Recognizing low vaccine safe, and well tolerated in females 9
lomatosis. Clinical trials have revealed
uptake among females and the prepon- through 26 years of age. Antibody re-
the vaccine to be highly immunogenic,
derance of heterosexual transmission in sponses are highest in girls 9 through
safe, and well tolerated in males and
the epidemiology of HPV, immunization 15 years of age. HPV2 is not licensed
females 9 through 26 years of age.
of males becomes a cost-effective in- for use in males.
Antibody responses are at least twice
tervention for preventing disease as high in individuals of both genders 9 The safety of HPV4 was evaluated in 2
caused by vaccine types of HPV in both through 15 years of age as in those 16 large phase III clinical trials in females,
genders. through 26 years of age. HPV4 was 1 phase III clinical trial in males, and
Other interventions to reduce HPV in- licensed for use in females in 2006; several immunogenicity studies in ad-
fection and HPV-associated genital antibodies have been shown to persist olescents. There is continued surveil-
warts and malignancies include coun- for at least 9 years. HPV4 was licensed lance of potential adverse effects of
seling of adolescents regarding sexu- for use in males in 2009; the duration HPV vaccine through the Vaccine Ad-
ality, including abstinence and proper of vaccine-induced antibodies is still verse Effect Reporting System as well
use of condoms, and circumcision under investigation but is known to be as real-time surveillance of large health
of males. HPV is transmitted skin to at least 5 years. maintenance organization practices via
skin, so protection by condoms is In sexually active female subjects 16 the Vaccine Safety Datalink. Several
imperfect.4–6 through 26 years of age, protection has other countries or communities con-
As a sidebar, there is precedent for been demonstrated against persistent duct similar surveillance for adverse
vaccines recommended by the AAP infection; precancerous lesions of the effects of HPV vaccines. The Food and
and the Advisory Committee on Immu- cervix, vulva, and vagina; and genital Drug Administration requires post-
nization Practices for prevention of sex- warts caused by HPV types contained marketing surveillance by vaccine
ually transmitted infections and cancer in the vaccine. The vaccine was manufacturers. After more than 40
and for immunization of all children recommended for females in 2007. In million doses have been adminis-
to minimize infectious complications sexually active male subjects 16 through tered in the first 5 years of routine
PEDIATRICS Volume 129, Number 3, March 2012 603

3. administration in American girls, no or completion of the immunization (ie, Papanicolaou testing) should
discernible, vaccine-specific adverse series. Patients infected with 1 HPV continue to be conducted in women
effect, with the exception of rare ana- type may still benefit from protec- who have received HPV vaccine.
phylaxis to vaccine components, has tion against remaining HPV types in 13. Administration of HPV vaccine
been detected. the vaccine. Testing for previous does not change current counsel-
exposure to HPV is not recommen- ing recommendations for use of
ded. HPV vaccine can be adminis- barrier methods for the preven-
RECOMMENDATIONS
tered when a female patient has an tion of HPV and other sexually
1. Girls 11 through 12 years of age abnormal or equivocal Papanicolaou transmitted infections as well as
should be immunized routinely test result. There is no known ther- discussion about healthy choices
with 3 doses of HPV4 or HPV2, ad- apeutic (as opposed to prophylac- about sexual activity, including
ministered intramuscularly at 0, 1 tic) benefit from the HPV vaccines. condoms and abstinence.
to 2, and 6 months. The vaccines 8. HIV-infected people of either gen- 14. HPV immunization of children 9
can be administered starting at der, 9 through 26 years of age, years of age and older should
9 years of age at the discretion who have not been immunized be covered by all public and pri-
of the physician. previously or have not completed vate health insurers.
2. All girls and women 13 through the full vaccine series should re-
26 years of age who have not ceive or complete their series CONTRAINDICATIONS
been immunized previously or with HPV4.
HPV4 should not be given to people
have not completed the full vac- 9. HPV vaccines can be administered with a history of immediate hyper-
cine series should complete the at the same visit as all other rec- sensitivity to yeast or to pregnant
series. ommended vaccines. women.
3. Boys 11 through 12 years of age 10. HPV vaccine can be administered
should be immunized routinely with in these special circumstances: PRECAUTIONS
3 doses of HPV4, administered in-
a. when a patient is immunocom- Immunizations should be deferred for
tramuscularly at 0, 1 to 2, and 6
promised because of disease or people with moderate or severe acute
months. The vaccine can be given
medication illness. Because syncope can occur in
starting at 9 years of age at the
b. when a female patient is adolescents after injections and has
discretion of the physician.
breastfeeding been reported after HPV vaccine,
4. All boys and men 13 through 21 11. HPV vaccine is not recommended vaccine recipients should sit or lie
years of age who have not been during pregnancy. The practitioner down for 15 minutes after adminis-
immunized previously or have not should inquire about pregnancy in tration.
completed the full vaccine series sexually active female patients, but
should receive HPV4 vaccine. a pregnancy test is not required IMPLEMENTATION
5. Men 22 through 26 years of age before starting the immunization
who have not been immunized These updated recommendations for
series. If a vaccine recipient be-
previously or have not completed HPV immunization will have consider-
comes pregnant, subsequent doses
the full vaccine series may re- able operational and fiscal effect on
should be postponed until comple-
ceive HPV4 vaccine. Cost-efficacy pediatric practice. Therefore, the AAP
tion of the pregnancy. It is recom-
has developed implementation guid-
models do not justify a stronger mended that women who become
ance on supply, payment, coding, and
recommendation in this age group. pregnant while receiving HPV vac-
liability issues; these documents can
6. Special effort should be given to cine be reported to registries that be found at www.aapredbook.org/
immunizing men who have sex have been developed to record data implementation.
with men up to 26 years of age on outcomes (HPV2: 1-888-452-9622;
who have not been immunized HPV4: 1-800-986-8999). COMMITTEE ON INFECTIOUS
previously or have not com- 12. Because HPV vaccine will not pre- DISEASES, 2011–2012
pleted the full vaccine series. Michael T. Brady, MD, Chairperson
vent infection attributable to all
Carrie L. Byington, MD
7. Previous sexual activity is not a con- high-risk HPV types, cervical can- H. Dele Davies, MD
traindication to HPV immunization cer screening recommendations Kathryn M. Edwards, MD
604 FROM THE AMERICAN ACADEMY OF PEDIATRICS

4. FROM THE AMERICAN ACADEMY OF PEDIATRICS
Mary P. Glode, MD R. Douglas Pratt, MD – Food and Drug Admin- EX OFFICIO
Mary Anne Jackson, MD istration Carol J. Baker, MD – Red Book Associate Editor
Harry L. Keyserling, MD Jennifer S. Read, MD – National Vaccine Pro- Henry H. Bernstein, DO – Red Book Associate
Yvonne A. Maldonado, MD gram Office Editor
Dennis L. Murray, MD Joan Robinson, MD – Canadian Paediatric So- David W. Kimberlin, MD – Red Book Associate
Walter A. Orenstein, MD ciety Editor
Gordon E. Schutze, MD Marco Aurelio Palazzi Safadi, MD – Sociedad Sarah S. Long, MD – Red Book Associate Editor
Rodney E. Willoughby, MD Latinoamericana de Infectologia Pediatrica H. Cody Meissner, MD – Red Book Associate
Theoklis E. Zaoutis, MD (SLIPE) Editor
Jane Seward, MBBS, MPH – Centers for Disease Larry K. Pickering, MD – Red Book Editor
Control and Prevention
LIAISONS Jane Seward, MBBS, MPH – Centers for Disease
Marc A. Fischer, MD – Centers for Disease Control and Prevention
CONSULTANT
Control and Prevention Jeffrey R. Starke, MD – American Thoracic
Lorry G. Rubin, MD
Bruce Gellin, MD – National Vaccine Program Society
Office Geoffrey Simon, MD – Committee on Practice
Richard L. Gorman, MD – National Institutes of Ambulatory Medicine
Health Tina Q. Tan, MD – Pediatric Infectious Diseases STAFF
Lucia Lee, MD – Food and Drug Administration Society Jennifer Frantz, MPH
REFERENCES
1. American Academy of Pediatrics. Human papillomavirus vaccine [Retired]. Pediat- adolescents. Pediatrics. 2001;107(6):1463–
papillomaviruses. In: Pickering LK, Baker CJ, rics. 2007;120(3):666–668 1469
Kimberlin DW, Long SS, eds. Red Book: 2009 3. Centers for Disease Control and Pre- 5. American Academy of Pediatrics, Com-
Report of the Committee on Infectious Dis- vention. Recommendations on the use of mittee on Adolescence. Male adolescent
eases. Elk Grove Village, IL: American Acad- quadrivalent human papillomavirus vac- sexual and reproductive health care. Pe-
emy of Pediatrics; 2009:477–483 cine in males—Advisory Committee on diatrics. 2011;128(6). Available at: www.
2. American Academy of Pediatrics Committee Immunization Practices (ACIP), 2011. MMWR pediatrics.org/cgi/content/full/128/6/
on Infectious Diseases. Prevention of human Morb Mortal Wkly Rep. 2011;(50):1705– e1658
papillomavirus infection: provisional rec- 1708 6. American Academy of Pediatrics, Task Force
ommendations for immunization of girls 4. American Academy of Pediatrics, Com- on Circumcision. Technical report: male
and women with quadrivalent human mittee on Adolescence. Condom use by circumcision. Pediatrics. 2012; in press
PEDIATRICS Volume 129, Number 3, March 2012 605