A statement of retirement for this policy was published at

136(3):e730

Pediatrics
March 2012, VOLUME 129 / ISSUE 3
From the American Academy of Pediatrics
Policy Statement

HPV Vaccine Recommendations

COMMITTEE ON INFECTIOUS DISEASES

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Abstract
On October 25, 2011, the Advisory Committee on Immunization Practices of the Centers for
Disease Control and Prevention recommended that the quadrivalent human papillomavirus
vaccine (Gardasil; Merck & Co, Inc, Whitehouse Station, NJ) be used routinely in males. The
American Academy of Pediatrics has reviewed updated data provided by the Advisory
Committee on Immunization Practices on vaccine efficacy, safety, and cost-effectiveness as
well as programmatic considerations and supports this recommendation. This revised
statement updates recommendations for human papillomavirus immunization of both males
and females.

KEY WORDS

human papillomavirus
HPV
vaccine
males
females
adolescents
immunization
cancer

Abbreviations:
AAP
American Academy of Pediatrics
HPV
human papillomavirus
HPV2
bivalent human papillomavirus vaccine
HPV4
quadrivalent human papillomavirus vaccine

Introduction
The American Academy of Pediatrics (AAP) recommends immunization against human
papillomavirus (HPV) for all 11- through 12-year-old children as part of the adolescent
immunization platform. Quadrivalent 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 permissive 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

Brief Background and Rationale

HPVs are the most common sexually transmitted viruses in the United States. The highest
prevalence of HPV infection is found in sexually active adolescents and young adults. Most
HPV infections are asymptomatic 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 15000 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 administered before onset of sexual
activity. The vaccine is inactive against HPV types previously acquired by the vaccine
recipient. Second, antibody responses are highest at ages 9 through 15 years. Immunization of
males provides direct benefit to males, including prevention of genital warts and anal cancer.
Prevention of oropharyngeal cancer has not been studied but is biologically plausible. In
addition, immunization of males is expected to provide indirect benefit for females through
herd immunity. Four years after the initial recommendation for immunization of females,
uptake of the HPV vaccine lags behind other vaccines offered in adolescence; results of the
2010 National Immunization Survey indicated 32% of females 13 through 17 years have
completed the 3-dose series. The cost-effectiveness of male immunization is sensitive to a
range of assumptions, such as vaccine efficacy, vaccine coverage of females, and the effect of
HPV-associated diseases on quality of life. Recognizing low vaccine uptake among females
and the preponderance of heterosexual transmission in the epidemiology of HPV,
immunization of males becomes a cost-effective intervention for preventing disease caused
by vaccine types of HPV in both genders.

Other interventions to reduce HPV infection and HPV-associated genital warts and
malignancies include counseling of adolescents regarding sexuality, including abstinence and
proper use of condoms, and circumcision of males. HPV is transmitted skin to skin, so
protection by condoms is imperfect.4,6
As a sidebar, there is precedent for vaccines recommended by the AAP and the Advisory
Committee on Immunization Practices for prevention of sexually transmitted infections and
cancer and for immunization of all children to minimize infectious complications
disproportionately affecting females during their reproductive years. Rubella vaccine (a
component of the measles-mumps-rubella vaccine) is intended primarily to prevent fetal
miscarriages and malformations after rubella infection during pregnancy, and hepatitis B
virus vaccine prevents cirrhosis of the liver and hepatocellular carcinoma caused by hepatitis
B virus acquired at time of birth or through later sexual exposure.

HPV Vaccines
HPV4 contains no viral DNA and is not infectious. It consists of bioengineered viruslike
particles produced from the major capsid protein of HPV types 16 and 18, which are
responsible for 70% of cases of cervical, 87% of anal, 60% of oropharyngeal, and 31% of
penile cancers. In addition, the vaccine includes capsid proteins of types 6 and 11, which are
responsible for 90% of genital warts and almost all cases of juvenile recurrent respiratory
papillomatosis. Clinical trials have revealed the vaccine to be highly immunogenic, safe, and
well tolerated in males and females 9 through 26 years of age. Antibody responses are at least
twice as high in individuals of both genders 9 through 15 years of age as in those 16 through
26 years of age. HPV4 was licensed for use in females in 2006; antibodies have been shown
to persist for at least 9 years. HPV4 was licensed for use in males in 2009; the duration of
vaccine-induced antibodies is still under investigation but is known to be at least 5 years.

In sexually active female subjects 16 through 26 years of age, protection has been
demonstrated against persistent infection; precancerous lesions of the cervix, vulva, and
vagina; and genital warts caused by HPV types contained in the vaccine. The vaccine was
recommended for females in 2007. In sexually active male subjects 16 through 26 years of
age, vaccine efficacy was demonstrated against genital warts caused by vaccine types. HPV4
was permitted in males in 2010. Also in 2010, the US Food and Drug Administration added a
new indication of prevention of anal cancer in males and females on the basis of data from an
efficacy study in males. In new data from a substudy of high-risk sexually active young men
(men who have sex with men), protection has been demonstrated against precancerous
lesions of the anus. These data contribute to the current recommendation. The study did not
have adequate power (too few penile or perineal precancerous lesions) to support benefit in
preventing these precancerous conditions. No studies of HPV4 vaccine protection against
oropharyngeal cancers or recurrent respiratory papillomatosis have been conducted.

HPV2, directed at HPV types 16 and 18, was licensed for use in females in 2009. This
vaccine is highly immunogenic, safe, and well tolerated in females 9 through 26 years of age.
Antibody responses are highest in girls 9 through 15 years of age. HPV2 is not licensed for
use in males.

The safety of HPV4 was evaluated in 2 large phase III clinical trials in females, 1 phase III
clinical trial in males, and several immunogenicity studies in adolescents. There is continued
surveillance of potential adverse effects of HPV vaccine through the Vaccine Adverse Effect
Reporting System as well as real-time surveillance of large health maintenance organization
practices via the Vaccine Safety Datalink. Several other countries or communities conduct
similar surveillance for adverse effects of HPV vaccines. The Food and Drug Administration
requires postmarketing surveillance by vaccine manufacturers. After more than 40 million
doses have been administered in the first 5 years of routine administration in American girls,
no discernible, vaccine-specific adverse effect, with the exception of rare anaphylaxis to
vaccine components, has been detected.

Recommendations
1. Girls 11 through 12 years of age should be immunized routinely with 3 doses of
HPV4 or HPV2, administered intramuscularly at 0, 1 to 2, and 6 months. The
vaccines can be administered starting at 9 years of age at the discretion of the
physician.
2. All girls and women 13 through 26 years of age who have not been immunized
previously or have not completed the full vaccine series should complete the series.
3. Boys 11 through 12 years of age should be immunized routinely with 3 doses of
HPV4, administered intramuscularly at 0, 1 to 2, and 6 months. The vaccine can be
given starting at 9 years of age at the discretion of the physician.
4. All boys and men 13 through 21 years of age who have not been immunized
previously or have not completed the full vaccine series should receive HPV4
vaccine.
5. Men 22 through 26 years of age who have not been immunized previously or have not
completed the full vaccine series may receive HPV4 vaccine. Cost-efficacy models do
not justify a stronger recommendation in this age group.
6. Special effort should be given to immunizing men who have sex with men up to 26
years of age who have not been immunized previously or have not completed the full
vaccine series.
7. Previous sexual activity is not a contraindication to HPV immunization or completion
of the immunization series. Patients infected with 1 HPV type may still benefit from
protection against remaining HPV types in the vaccine. Testing for previous exposure
to HPV is not recommended. HPV vaccine can be administered when a female patient
has an abnormal or equivocal Papanicolaou test result. There is no known therapeutic
(as opposed to prophylactic) benefit from the HPV vaccines.
8. HIV-infected people of either gender, 9 through 26 years of age, who have not been
immunized previously or have not completed the full vaccine series should receive or
complete their series with HPV4.
9. HPV vaccines can be administered at the same visit as all other recommended
vaccines.
10. HPV vaccine can be administered in these special circumstances:
o a. when a patient is immunocompromised because of disease or medication
o b. when a female patient is breastfeeding
11. HPV vaccine is not recommended during pregnancy. The practitioner should inquire
about pregnancy in sexually active female patients, but a pregnancy test is not
required before starting the immunization series. If a vaccine recipient becomes
pregnant, subsequent doses should be postponed until completion of the pregnancy. It
is recommended that women who become pregnant while receiving HPV vaccine be
reported to registries that have been developed to record data on outcomes (HPV2: 1-
888-452-9622; HPV4: 1-800-986-8999).
12. Because HPV vaccine will not prevent infection attributable to all high-risk HPV
types, cervical cancer screening recommendations (ie, Papanicolaou testing) should
continue to be conducted in women who have received HPV vaccine.
13. Administration of HPV vaccine does not change current counseling recommendations
for use of barrier methods for the prevention of HPV and other sexually transmitted
 infections as well as discussion about healthy choices about sexual activity, including
condoms and abstinence.
14. HPV immunization of children 9 years of age and older should be covered by all
public and private health insurers.

Contraindications
HPV4 should not be given to people with a history of immediate hypersensitivity to yeast or
to pregnant women.

Precautions
Immunizations should be deferred for people with moderate or severe acute illness. Because
syncope can occur in adolescents after injections and has been reported after HPV vaccine,
vaccine recipients should sit or lie down for 15 minutes after administration.

Implementation
These updated recommendations for HPV immunization will have considerable operational
and fiscal effect on pediatric practice. Therefore, the AAP has developed implementation
guidance on supply, payment, coding, and liability issues; these documents can be found at
www.aapredbook.org/implementation.

Committee on Infectious Diseases, 20112012

Michael T. Brady, MD, Chairperson

Carrie L. Byington, MD

H. Dele Davies, MD

Kathryn M. Edwards, MD

Mary P. Glode, MD

Mary Anne Jackson, MD

Harry L. Keyserling, MD

Yvonne A. Maldonado, MD

Dennis L. Murray, MD

Walter A. Orenstein, MD

Gordon E. Schutze, MD

Rodney E. Willoughby, MD
Theoklis E. Zaoutis, MD

Liaisons
Marc A. Fischer, MD Centers for Disease Control and Prevention

Bruce Gellin, MD National Vaccine Program Office

Richard L. Gorman, MD National Institutes of Health

Lucia Lee, MD Food and Drug Administration

R. Douglas Pratt, MD Food and Drug Administration

Jennifer S. Read, MD National Vaccine Program Office

Joan Robinson, MD Canadian Paediatric Society

Marco Aurelio Palazzi Safadi, MD Sociedad Latinoamericana de Infectologia Pediatrica

(SLIPE)

Jane Seward, MBBS, MPH Centers for Disease Control and Prevention

Jane Seward, MBBS, MPH Centers for Disease Control and Prevention

Jeffrey R. Starke, MD American Thoracic Society

Geoffrey Simon, MD Committee on Practice Ambulatory Medicine

Tina Q. Tan, MD Pediatric Infectious Diseases Society

Ex Officio
Carol J. Baker, MD Red Book Associate Editor

Henry H. Bernstein, DO Red Book Associate Editor

David W. Kimberlin, MD Red Book Associate Editor

Sarah S. Long, MD Red Book Associate Editor

H. Cody Meissner, MD Red Book Associate Editor

Larry K. Pickering, MD Red Book Editor

Consultant
Lorry G. Rubin, MD
Staff
Jennifer Frantz, MPH

Footnotes
This document is copyrighted and is property of the American Academy of Pediatrics
and its Board of Directors. All authors have filed conflict of interest statements with
the American Academy of Pediatrics. Any conflicts have been resolved through 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 this publication.
All policy statements from the American Academy of Pediatrics automatically expire
5 years after publication unless reaffirmed, revised, or retired at or before that time.

References
1.
1. American Academy of Pediatrics

. Human papillomaviruses. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds.
Red Book: 2009 Report of the Committee on Infectious Diseases. Elk Grove Village,
IL: American Academy of Pediatrics; 2009:477483

2.
1. American Academy of Pediatrics Committee on Infectious Diseases

. Prevention of human papillomavirus infection: provisional recommendations for

immunization of girls and women with quadrivalent human papillomavirus vaccine
[Retired]. Pediatrics. 2007;120(3):666668pmid:17766541

3.
1. Centers for Disease Control and Prevention

. Recommendations on the use of quadrivalent human papillomavirus vaccine in

malesAdvisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb
Mortal Wkly Rep. 2011;(50):17051708

4.
1. American Academy of Pediatrics, Committee on Adolescence

. Condom use by adolescents. Pediatrics. 2001;107(6):14631469

5. American Academy of Pediatrics, Committee on Adolescence. Male adolescent

sexual and reproductive health care. Pediatrics. 2011;128(6). Available at:
www.pediatrics.org/cgi/content/full/128/6/e1658
6.
 American Academy of Pediatrics, Task Force on Circumcision. Technical report:
male circumcision. Pediatrics. 2012; in press

Copyright 2012 by the American Academy of Pediatrics

http://pediatrics.aappublications.org/content/129/3/602

Q: How common are HPV infections?

A: HPV infections are so common that nearly all men and women will get at least one type of
HPV at some point in their lives. Most people never know that they have been infected and
may give HPV to a sex partner without knowing it. About 79 million Americans are currently
infected with some type of HPV. About 14 million people in the United States become newly
infected each year.

Q: What kinds of problems does HPV infection cause?

A: Most people with HPV never develop symptoms or health problems. Most HPV infections
(9 out of 10) go away by themselves within two years. But, sometimes, HPV infections will
last longer, and can cause certain cancers and other diseases. HPV infections can cause:

cancers of the cervix, vagina, and vulva in women;

cancers of the penis in men; and
cancers of the anus and back of the throat, including the base of the tongue and tonsils
(oropharynx), in both women and men. Every year in the United States, HPV causes
30,700 cancers in men and women.

Q: How do people get an HPV infection?

A: People get HPV from another person during intimate sexual contact. Most of the time,
people get HPV from having vaginal and/or anal sex. Men and women can also get HPV
from having oral sex or other sex play. A person can get HPV even if their partner doesnt
have any signs or symptoms of HPV infection. A person can have HPV even if years have
passed since he or she had sexual contact with an infected person. Most people do not realize
they are infected. They also dont know that they may be passing HPV to their sex partner(s).
It is possible for someone to get more than one type of HPV.

It's not very common, but sometimes a pregnant woman with HPV can pass it to her baby
during delivery. The child might develop recurrent respiratory papillomatosis (RRP), a rare
but dangerous condition where warts caused by HPV (similar to genital warts) grow inside
the throat.

There havent been any documented cases of people getting HPV from surfaces in the
environment, such as toilet seats. However, someone could be exposed to HPV from objects
(toys) shared during sexual activity if the object has been used by an infected person.
Top of Page

Q: Who should get HPV vaccine?

A: All girls and boys who are 11 or 12 years old should get the recommended series of HPV
vaccine. The vaccination series can be started at age 9 years. Teen boys and girls who did not
get vaccinated when they were younger should get it now. HPV vaccine is recommended for
young women through age 26, and young men through age 21. HPV vaccine is also
recommended for the following people, if they did not get vaccinated when they were
younger:

young men who have sex with men, including young men who identify as gay or
bisexual or who intend to have sex with men through age 26;
young adults who are transgender through age 26; and
young adults with certain immunocompromising conditions (including HIV) through
age 26.

Q: Why are two doses recommended for 914 year olds, while older
adolescents need three doses?

A: Since 2006, HPV vaccines have been recommended in a three-dose series given over six
months. In 2016, CDC changed the recommendation to two doses for persons starting the
series before their 15th birthday. The second dose of HPV vaccine should be given six to
twelve months after the first dose. Adolescents who receive their two doses less than five
months apart will require a third dose of HPV vaccine.

Teens and young adults who start the series at ages 15 through 26 years still need three doses
of HPV vaccine Also, three doses are still recommended for people with certain
immunocompromising conditions aged 9 through 26 years.

CDC makes recommendations based on the best available scientific evidence. Studies have
shown that two doses of HPV vaccine given at least six months apart to adolescents at age 9
14 years worked as well or better than three doses given to older adolescents and young
adults. Studies have not been done to show this for adolescents starting the series at age 15
years or older.

Q: Why is HPV vaccine recommended at age 11 or 12 years?

A: For HPV vaccine to be most effective, the series should be given prior to exposure to
HPV. There is no reason to wait to vaccinate until teens reach puberty or start having sex.
Preteens should receive all recommended doses of the HPV vaccine series long before they
begin any type of sexual activity.
Q: How well does HPV vaccine work?

A: HPV vaccines work extremely well. Clinical trials showed HPV vaccines provide close to
100% protection against cervical precancers and genital warts. Since the first HPV vaccine
was recommended in 2006, there has been a 64% reduction in vaccine-type HPV infections
among teen girls in the United States. Studies have shown that fewer teens are getting genital
warts and cervical precancers are decreasing. In other countries, such as Australia, where
HPV vaccination coverage is higher than in the United States, large decreases have been
observed in these HPV-associated outcomes. HPV vaccines offer long-lasting protection
against HPV infection and HPV disease. There has been no evidence to suggest that HPV
vaccine loses any ability to provide protection over time. Data are available for about 10
years of follow-up after vaccination.

Like all vaccines, HPV vaccine is monitored on an ongoing basis to make sure it remains safe
and effective. If it turns out that protection from HPV vaccine is not long-lasting, then the
Advisory Committee on Immunization Practices would review the data and determine
whether a booster dose would be recommended.

Even if it has been months or years since the last shot, the HPV vaccine series should be
completedbut they do not need to restart the series.

HPV vaccine is recommended based on age, not sexual experience. Even if someone has
already had sex, they should still get HPV vaccine. Even though a persons first HPV
infection usually happens during one of the first few sexual experiences, a person might not
be exposed to all of the HPV types that are covered by HPV vaccines.

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Q: Does HPV vaccination offer similar protection from cervical cancer in all
racial/ethnic groups?

A: Yes. Several different HPV types cause cervical cancer. HPV vaccines are designed to
prevent the HPV types that cause most cervical cancers, so HPV vaccination will provide
high protection for all racial/ethnic groups.

All three licensed HPV vaccines protect against types 16 and 18, which cause the majority of
cervical cancers across racial/ethnic groups (67% of the cervical cancers among whites, 68%
among blacks, and 64% among Hispanics). The 9-valent HPV vaccine protects against seven
HPV types that cause about 80% of cervical cancer among all racial/ethnic groups in the
United States.

Teens and young adults who havent completed the HPV vaccine series should make an
appointment today to get vaccinated. To protect against cervical cancer, women age 2165
years should get screened for cervical cancer at regular intervals and get follow-up care as
recommended by their doctor or nurse.

Q: How do we know that the HPV vaccine is safe?

A: The United States currently has the safest, most effective vaccine supply in history. Years
of testing are required by law to ensure the safety of vaccines before they are made available
for use in the United States. This process can take ten years or longer. Once a vaccine is in
use, CDC and the Food and Drug Administration (FDA) monitor any associated side effects
or possible side effects (adverse events) through the Vaccine Adverse Event Reporting
System and other vaccine safety systems.

All three HPV vaccinesCervarix, Gardasil, and Gardasil 9went through years of
extensive safety testing before they were licensed by FDA. Cervarix was studied in clinical
trials with more than 30,000 females. Gardasil trials included more than 29,000 females and
males, and Gardasil 9 trials included more than 15,000 females and males. No serious safety
concerns were identified in these clinical trials. FDA only licenses a vaccine if it is safe,
effective, and the benefits outweigh the risks. CDC and FDA continue to monitor HPV
vaccines to make sure they are safe and beneficial for the public.

Q: What are the possible side effects of HPV vaccination?

A: Vaccines, like any medicine, can have side effects. Many people who get HPV vaccine
have no side effects at all. Some people report having very mild side effects, like a sore arm.
The most common side effects are usually mild. Common side effects of HPV vaccine
include:

Pain, redness, or swelling in the arm where the shot was given
Fever
Headache or feeling tired
Nausea
Muscle or joint pain

Brief fainting spells and related symptoms (such as jerking movements) can happen after any
medical procedure, including vaccination. Sitting or lying down while getting a shot and then
staying that way for about 15 minutes can help prevent fainting and injuries caused by falls
that could occur from fainting.

On very rare occasions, severe (anaphylactic) allergic reactions may occur after vaccination.
People with severe allergies to any component of a vaccine should not receive that vaccine.

HPV vaccine does not cause HPV infection or cancer. HPV vaccine is made from one protein
from the virus, and is not infectious, meaning that it cannot cause HPV infection or cancer.
Not receiving HPV vaccine at the recommended ages can leave one vulnerable to cancers
caused by HPV.

There are no data that suggest getting HPV vaccine will have an effect on future fertility for
women. In fact, getting vaccinated and protecting against HPV-related cancers can help
women and families have healthy pregnancies and healthy babies.

Not getting HPV vaccine leaves people vulnerable to HPV infection and related cancers.
Treatments for cancers and precancers might include surgery, chemotherapy, and/or
radiation, which might cause pregnancy complications or leave someone unable to have
children.

Q: Why is this vaccine not mandatory for school entry?

A: Each state determines which vaccines are required for school entry. Many factors are
taken into consideration before requiring any vaccine for school entry, including: community
support for the requirement, financial resources needed to implement the requirement, burden
on school personnel for enforcing the requirement, vaccine supply, and current vaccination
coverage levels.

Since almost every state requires Tdap (tetanus, diphtheria, and acellular pertussis vaccine)
for middle school entry, parents can use this visit to the doctor to get the first HPV and
quadrivalent meningococcal conjugate vaccines for their preteen at the same time.

Q: How can someone get help paying for HPV vaccine?

A: The Vaccines for Children (VFC) program helps families of eligible children who might
not otherwise have access to vaccines. The program provides vaccines at no cost to children
ages 18 years and younger who are uninsured, Medicaid-eligible, or American Indian/Alaska
Native. To learn more, see VFC program.

Top of Page

Page last reviewed: November 21, 2016

Page last updated: November 28, 2016
Content source:
o National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention;
National Center for Immunization and Respiratory Diseases; National Center
for Chronic Disease Prevention and Health Promotion
Page maintained by: National Center for Immunization and Respiratory
Diseases

https://www.cdc.gov/hpv/parents/questions-answers.html

1600 Clifton Road Atlanta, GA 30329-4027 USA

800-CDC-INFO (800-232-4636), TTY: 888-232-6348
Email CDC-INFO
U.S. Department of Health & Human Services
HHS/Open
USA.gov
A. What is HPV
HPV is the most common sexually transmitted infection in the United States. Some strains of
HPV are responsible for warts on the hands and feet, and other strains cause warts of the
penis, scrotum, vulva, vagina, anus, rectum, urethra, cervix and mouth. HPV is spread
through skin-to-skin and mucous membrane contact during sexual activity. HPV can be
spread in the absence of vaginal and rectal intercourse.

Research has shown that 99.7 percent of cervical cancers are caused by HPV infection. There
are more than 150 different types of HPV, of which more than 40 have been linked to genital
tract infections and cancer. Genital HPV types are divided into low- and high-risk types
based on their potential to cause cervical and other lower genital tract cancers.

What subtypes of the virus are of greatest concern?

HPV types 6 and 11 are the most common low-risk types, causing about 90 percent of genital
and respiratory warts (Recurrent Respiratory Papillomatosis or RRP). HPV types 16 and 18
are the most common high-risk types, causing about 70 percent of cervical cancers. These
high-risk HPV types are also known to cause some cancers of the anus, oropharynx, vulva,
vagina and penis. The subtypes that cause warts do not cause cancer.

What is the burden of HPV infections?

It is estimated that 20 million people nationwide are infected with HPV, and more than 6
million new HPV infections are diagnosed each year. Based on national estimates, 50 percent
of sexually active men and women will acquire HPV infection at some point in their lives.
Females, ages 20-24, have the highest prevalence of both high- and low-risk types of HPV.

The majority of genital HPV infections are transient, asymptomatic and clinically
unrecognizable. Furthermore, about 90 percent of HPV infections will resolve without
treatment within two years. The HPV infections that are not eliminated can lead to cervical or
other cancers, genital warts or, rarely, warts in the throat.

What are the health effects of HPV infection?

While usually asymptomatic, depending on the strain, genital or rectal warts may appear soon
after infection. Although HPV is usually cleared by an individual's immune system a few
months following infection, the virus can persist for long periods of time due to host, viral
and environmental factors, and be triggered years later to cause symptoms such as warts or
precancerous changes.

HPV is the only known cause of cervical cancer and is linked to oral, anal, vulvar, vaginal
and penile cancers. Annually, in the United States, approximately 12,000 women are
diagnosed with cervical cancer, with about 4,000 eventually dying from this disease.

HPV-associated cancers in males include certain anal, penile and oropharyngeal cancers and
dysplasia. About 25 percent of HPV-related cancers occur in males.
How is HPV transmitted?

HPV is an extremely contagious virus that is transmitted through skin-to-skin and mucous
membrane contact during sexual activity. HPV transmission can occur in the oral, anal or
genital regions even in the absence of intercourse. HPV is difficult to identify and avoid in
sexually active people because it is often not possible to see the lesions.

B. HPV Vaccine
Is there a vaccine that prevents HPV infection?

Yes. There are currently two vaccines, Gardasil (HPV4) and Cervarix (HPV2). Both provide
protection against HPV types 16 and 18, which cause most cases of cervical cancer. Gardasil
(HPV4) also protects against HPV types 6 and 11, which cause most types of genital and
respiratory warts. The HPV vaccine is very effective in preventing infection from the strains
of HPV that cause 7 out of 10 cases of cervical cancer and 9 out of 10 cases of genital warts.

Both vaccines are currently administered in three doses over 6 months.

The first dose is recommended to be given at ages 11-12.

The second dose should be given 1 to 2 months after Dose 1.
The third dose should be given 6 months after Dose 1.

Catch-up vaccination is recommended for those who do not complete the three dose series.

There are two vaccines available for protecting females against HPV:

1. Gardasil (HPV4):

Licensed by the U.S. Food and Drug Administration (FDA) and recommended by the
Advisory Committee on Immunization Practices (ACIP) in 2006;
For use in females ages 9-26;
Protects against cervical cancer, and some vulvar and vaginal cancers, caused by HPV
types 16 and 18;
Protects against anal cancer and precancerous anal lesions caused by HPV types 6 and
11.

2. Cervarix (HPV2):

Licensed by the FDA and recommended by ACIP in 2009;

For use in females ages 10-25 ONLY;
Protects against cervical cancer, and some vulvar and vaginal cancers, caused by HPV
types 16 and 18;

There is one vaccine for protecting males against HPV:

Gardasil (HPV4)

Licensed by the FDA in 2009 and recommended by ACIP in 2011;

 For use in males ages 9-26;
Protects against anal cancer and precancerous anal lesions caused by HPV types 6 and
11.

Who should get an HPV vaccine?

ACIP recommends routine HPV vaccination for females and males ages 11 to 12. Catch-up
vaccination is recommended for those who did not complete the three dose series.

What are the benefits of an HPV vaccine?

HPV vaccines prevent 7 out of 10 cases of cervical cancer and 9 out of 10 cases of genital
warts. HPV vaccination has been found to be extremely effective in preventing the
precancerous cervical cell changes that HPV 16 and 18 would cause. Gardasil (HPV4) has
also been shown to protect against anal, vaginal and vulvar cancers. In addition, the vaccines
also significantly reduce false positive Pap tests, thus reducing the number of costly and
potentially unnecessary diagnostic procedures performed on women. In total, the vaccines
have a tremendous benefit on the health care of women and men.

What is the vaccine's duration of protection?

While vaccination should be completed before initiation of sexual activity, information on the
duration of the vaccine's protection is incomplete. Studies show that serum antibody levels
remain high after HPV vaccination for up to eight years. No test is available for serologic
correlates of protection after vaccination. Ongoing studies are investigating whether
vaccinated individuals will need a booster in future years.

How many doses are required to complete the series?

Both Gardasil (HPV4) and Cervarix (HPV2) are given as a three-dose series: an initial dose
followed by doses at 1 or 2 months and 6 months. Providers should use the recommended
routine dosing intervals for series catch-up. The minimum interval between the first and
second dose is 4 weeks. The minimum interval between the second and third dose is 12
weeks. The third dose should be administered at least 24 weeks after the first dose.

How safe is the vaccine? What are the side effects?

Both HPV vaccines are very safe. Clinical trials, which have included tens of thousands of
people from all over the world, have not shown any serious adverse side effects. Since the
vaccines were licensed, no serious side effects have been shown to be caused by either
Gardasil (HPV4) or Cervarix (HPV2). However, a higher proportion of fainting and blood
clots have occurred with Gardasil (HPV4) than usually seen with other vaccines. For this
reason, to prevent head injuries resulting from fainting, the CDC recommends that
individuals remain lying or seated for 15 minutes after vaccination with Gardasil (HPV4).

Common minor side effects reported after vaccine administration include: pain at the
injection site, fever, dizziness and nausea. The CDC and FDA continue to monitor the safety
of these and every vaccine very carefully.
Why are 11- and 12-year-olds the priority age for the vaccine?

For HPV vaccine to work best, it is important to fully vaccinate both females and males
before they have their first sexual encounters and risk becoming infected with HPV. Fifteen-
to 25-year-olds have the highest prevalence of HPV infection. Vaccination must, therefore,
occur earlier in adolescence.

There is also evidence that the vaccine has a two to three times greater immunogenicity when
given to females ages 9-11 compared to females ages 15-25.

Do women need to continue to get Pap tests?

Yes. Both Gardasil (HPV4) and Cervarix (HPV2) only protect against the high-risk HPV
types that cause 7 out of 10 cases of cervical cancer. Because it is not known how long the
vaccine will protect against HPV, it is important for all women, even those who have been
vaccinated against HPV, to see their health care professionals for continued Pap screening.

C. HPV Vaccine Cost and Reimbursement

How much does the HPV vaccine cost?

The cost of both Gardasil (HPV4) and Cervarix (HPV2) range from approximately $95.00 to
$130.00 per dose and $285.00 to $390.00 for the complete series. Vaccination costs may vary
depending on the setting, so it is best to contact your practice administrator and/or your
patient's insurance carrier for specific pricing.

Will insurance companies provide reimbursement for the vaccine?

ACIP recommends HPV vaccination for females and males, with routine immunization
between 11 and 12 years of age. The Vaccines for Children (VFC) program covers the cost of
the HPV vaccine for all VFC-eligible children through the age of 18.

All private insurance plans regulated by New York State are required to cover the cost of all
ACIP-recommended vaccines, including HPV, for their patients through the age of 18. All
other private insurance plans should be contacted individually to determine their coverage of
HPV vaccination.

What if someone is uninsured or underinsured?

Uninsured and underinsured individuals under the age of 19 are eligible for the VFC program
and can receive vaccines at no cost.

In addition, both Merck and GSK have patient assistance programs which offer help for
individuals 19-26 years of age who cannot afford HPV vaccination.

The Merck Vaccine Patient Assistance Program (1-800-293-3881) offers free Gardasil
(HPV4) vaccine to people 19-26 years of age who are under or uninsured and cannot afford
to pay for the vaccine.
GSK's Vaccine Access Program (1-877-822-2911) provides free Cervarix (HPV2) to any
female 19-25 years of age who does not have insurance or cannot afford to pay for the
vaccine.

D. Answering Parents' Questions about HPV and HPV

Vaccination
This section provides information to help you answer parents' common questions about HPV
and the HPV vaccine.

How can people reduce the risk of HPV infection?

There are a number of ways that people can lower their chances of contracting HPV.

Get vaccinated. Vaccines against some of the most common types of HPV are
available for both males and females. The HPV vaccines are most effective when
administered prior to a person's first sexual encounter. In addition, for the best
protection against HPV, all three doses of the vaccine should be administered.
Practice abstinence. Defined as never having engaged in any type of sexual activity
with another person, abstinence is the most effective way to prevent HPV. However,
it should be remembered, that HPV can still be spread during sexual activity other
than vaginal, rectal or oral intercourse.
Limit the number of sex partners, be in a faithful relationship and choose a
partner with no or few prior sex partners. These practices can lower a person's
chances of contracting HPV. However, even people with only one lifetime sex partner
can get HPV.
Use condoms. Condoms may lower the risk of contracting HPV; however, HPV can
infect areas of one's body which are not covered by a condom.
Avoid sexual contact if one's partner is known to have HPV and is having (or
recently had) an outbreak of genital warts.

Is HPV different from HIV and herpes?

It is important that patients realize that although HPV, HIV and herpes are all sexually
transmitted viruses, they do not cause the same health problems or symptoms; nor are they
treated or prevented by the same methods or medications. For further information on these
other viruses please refer to the NYSDOH and the CDC.

Why are boys currently recommended to receive the HPV Vaccine?

Gardasil (HPV4) is currently licensed, safe and effective for males ages 9 through 26 years
of age.

The HPV vaccine protects males against the types of HPV that cause about 90 percent
of anal and genital warts.
About one-third of all cancers caused by HPV occur in males.
HPV has been linked to anal, penile and throat cancers in men.
Immunized boys will be less likely to spread cancer-causing types of HPV to their
sexual partners, thus decreasing disease in both males and females.
Does the HPV vaccine lead to increased sexual activity among teens?

Making sexual activity safer does not cause teens to become sexually active at an earlier age.
To date, there is no evidence that receiving the HPV vaccine encourages earlier initiation of
sex or increased sexual activity. According to a 2012 national study by the CDC published in
the American Journal of Preventive Medicine, younger females who received the HPV
vaccine did not have any higher rates of sexual promiscuity when compared to unvaccinated
females of similar ages (Liddon N. et al., 2012). Interestingly, among sexually active
adolescent females aged 15-19 years, the vaccinated females were more likely to report
consistent condom use by their partners in the past four weeks, than the unvaccinated females
of similar age.

Adolescents should be reminded that there are still many risks associated with sexual activity,
including pregnancy, HIV, herpes and other sexually transmitted infections (STIs). Safe
sexual practices, including condom use, should be reinforced at all adolescent patient
encounters.

Parents are the primary educators for teens on sexuality. Parents can weaken the power that
negative outside influences, such as peer pressure, have on their children by talking to them
about sexual health and relationships. Research has shown that informed teenagers, and
teenagers with involved parents, are more likely to delay the initiation of sexual behavior
(Deptula DP et al., 2010 and Rose A et al., 2005).

Parents can have their children vaccinated and still tell them that they shouldn't have sex as a
teenager. Having their child vaccinated is sending them the message that when they do
become sexually active, they should do so as safely as possible.

Why should my child be vaccinated at age 11 or 12? They are not sexually
active yet. Can't we wait?

Many parents have difficulty imagining a time when their child will become sexually active.
However, given that at least 20 percent of all 15-year-olds have already engaged in vaginal
sex, it is never too early to start thinking about the future sexual health of a child. In addition,
when it is given at ages 11 or 12, the vaccine has been shown to produce a better immune
response compared with older ages. The 11/12-year-old well child exam provides a unique
opportunity to educate both parents and adolescents about HPV and the HPV vaccine.

For the HPV vaccine to be most effective, children need to be vaccinated before they come
into contact with HPV. Once they are infected with the virus, it's too late for the vaccine to
protect them. We don't plan to get the flu or tetanus, but we get vaccinated against them so
that we are protected in the future.

In addition, research has shown that the HPV vaccine produces higher levels of antibodies
that fight HPV infection when given to children aged 9 to 11 compared to older adolescents.

Even if a child isn't sexually active they are protected from the most common types of HPV
infection. However, statistics indicate that as many as 25 percent of all 15-year-olds and 50
percent of all 17 -year-olds are sexually active. Parents can protect their children's health by
making sure they receive the HPV vaccine.
Girls who are vaccinated are protected from the types of HPV that cause:

8 out of 10 cases of anal cancer,

7 out of 10 cases of cervical cancer,
5 out of 10 cases of vaginal cancer, and
4 out of 10 cases of vulvar cancer.

Boys who are vaccinated are protected from the types of HPV that cause:

8 out of 10 cases of anal cancer, and

3 out of 10 cases of penile cancer.

References:
Deptula DP, Henry DB, Schoeny ME. How can parents make a difference? Longitudinal
associations with adolescent sexual behavior. Journal of Family Psychology 2010
Dec;24(6):731-9.

Rose A, Koo HP, Bhaskar B, Anderson K, white G, Jenkins RR. The influence of primary
caregivers on the sexual behavior of early adolescents. Journal of Adolescent health 2005
Aug;37(2):135-44.

https://www.health.ny.gov/prevention/immunization/providers/hpv_q_and_a.htm

Human Papillomavirus
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Human Papillomavirus
Pathogenesis
Clinical Features
Laboratory Diagnosis
Medical Management

Epidemiology
Disease Burden in the United States
Prevention
Human Papillomavirus Vaccine
 Vaccination Schedule and Use

Contraindications and Precautions to Vaccination

Adverse Reactions Following Vaccination
Vaccine Storage and Handling
Supplement

Human papillomavirus (HPV) is the most common sexually transmitted infection in the
United States. The relationship of cervical cancer and sexual behavior was suspected for
more than 100 years and was established by epidemiologic studies in the 1960s. In the early
1980s, cervical cancer cells were demonstrated to contain HPV DNA. Epidemiologic studies
showing a consistent association between HPV and cervical cancer were published in the
1990s. The first vaccine to prevent infection with four types of HPV was licensed in 2006.

Top of Page

Human Papillomaviruses (HPV)

Small DNA virus

More than 120 types identified based on the genetic sequence of the outer capsid protein L1
About 40 types infect the mucosal epithelium

Human Papillomavirus Types and Disease Association

Human Papillomaviruses
Human papillomaviruses are small, double-stranded DNA viruses that infect the epithelium.
More than 120 HPV types have been identified; they are differentiated by the genetic
sequence of the outer capsid protein L1. Most HPV types infect the cutaneous epithelium and
can cause common skin warts. About 40 types infect the mucosal epithelium; these are
categorized according to their epidemiologic association with cervical cancer. Infection with
low-risk, or nononcogenic types, such as types 6 and 11, can cause benign or low-grade
cervical cell abnormalities, genital warts and laryngeal papillomas. High-risk, or oncogenic,
HPV types act as carcinogens in the development of cervical cancer and other anogenital
cancers. High-risk types (currently including types 16 and 18, among others) can cause low-
grade cervical cell abnormalities, high-grade cervical cell abnormalities that are precursors to
cancer, and anogenital cancers. High-risk HPV types are detected in 99% of cervical cancers.
Type 16 is the cause of approximately 50% of cervical cancers worldwide, and types 16 and
18 together account for about 70% of cervical cancers. Infection with a high-risk HPV type is
considered necessary for the development of cervical cancer, but by itself it is not sufficient
to cause cancer because the vast majority of women with HPV infection do not develop
cancer.

In addition to cervical cancer, HPV infection is also associated with anogenital cancers less
common than cervical cancer, such as cancer of the vulva, vagina, penis and anus. The
association of genital types of HPV with non-genital cancers is less well established, but
studies support a role for these HPV types in some oropharyngeal cancers.

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Pathogenesis
Natural History of HPV Infection

HPV infection occurs at the basal epithelium. Although the incidence of infection is high,
most infections resolve spontaneously. A small proportion of infected persons become
persistently infected; persistent infection is the most important risk factor for the development
of cervical cancer. The most common clinically significant manifestation of persistent genital
HPV infection is cervical intraepithelial neoplasia, or CIN. Within a few years of infection,
low-grade CINcalled CIN 1may develop, which may spontaneously resolve and the
infection clear.

Persistent HPV infection, however, may progress directly to higher-grade CIN, called CIN2
or CIN3. High-grade abnormalities are at risk of progression to cancer and so are considered
cancer precursors. Some high-grade abnormalities spontaneously regress. If left undetected
and untreated, years or decades later CIN2 or 3 can progress to cervical cancer.

Infection with one type of HPV does not prevent infection with another type. Of persons
infected with mucosal HPV, 5% to 30% are infected with multiple types of the virus.

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Clinical Features
HPV Clinical Features

Most HPV infections are asymptomatic and result in no clinical disease

Clinical manifestations of HPV infection include:
o anogenital warts
 o recurrent respiratory papillomatosis
o cervical cancer precursors (cervical intraepithelial neoplasia)
o cancer (cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancer)

Most HPV infections are asymptomatic and result in no clinical disease. Clinical
manifestations of HPV infection include anogenital warts, recurrent respiratory
papillomatosis, cervical cancer precursors (cervical intraepithelial neoplasia), and cancers,
including cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancer.

Laboratory Diagnosis
HPV has not been cultured by conventional methods. Infection is identified by detection of
HPV DNA from clinical samples. Assays for HPV detection differ considerably in their
sensitivity and type specificity, and detection is also affected by the anatomic region sampled
as well as the method of specimen collection.

Several HPV tests have been approved by the Food and Drug Administration (FDA) and
detect 13-14 high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). Test
results are reported as positive or negative for any of the types; some tests specifically
identify HPV 16 and 18. These tests are approved for triage of Papanicolaou (Pap) test results
(ASC-US, atypical cells of undetermined significance) and in combination with the Pap test
for cervical cancer screening in women 30 years of age and older. The tests are not clinically
indicated nor approved for use in men.

Epidemiologic and basic research studies of HPV generally use nucleic acid amplification
methods that generate type-specific results. The polymerase chain reaction (PCR) assays used
most commonly in epidemiologic studies target genetically conserved regions in the L1 gene.

The most frequently used HPV serologic assays are virus-like particle (VLP)-based enzyme
immunoassays. However, laboratory reagents used for these assays are not standardized and
there are no standards for setting a threshold for a positive result.

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Medical Management
There is no specific treatment for HPV infection. Medical management depends on treatment
of the specific clinical manifestation of the infection (such as genital warts or abnormal
cervical cell cytology).

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Epidemiology
HPV Epidemiology

Reservoir
o Human
 Transmission
o Direct contact, usually sexual
Temporal pattern
o None
Communicability
o Presumed to be high

Occurrence

HPV infection occurs throughout the world.

Reservoir

Viruses in the papillomavirus family affect other species. Humans are the only natural
reservoir of HPV.

Transmission

HPV is transmitted by direct contact, usually sexual, with an infected person. Transmission
occurs most frequently with sexual intercourse but can occur following nonpenetrative sexual
activity.

Studies of newly acquired HPV infection demonstrate that infection occurs soon after onset
of sexual activity. In a prospective study of college women, the cumulative incidence of
infection was 40% by 24 months after first sexual intercourse. HPV 16 accounted for 10.4%
of infections.

Genital HPV infection also may be transmitted by nonsexual routes, but this appears to be
uncommon. Nonsexual routes of genital HPV transmission include transmission from a
woman to a newborn infant at the time of birth.

Temporal Pattern

There is no known seasonal variation in HPV infection.

Communicability

HPV is presumably communicable during the acute infection and during persistent infection.
This issue is difficult to study because of the inability to culture the virus. Communicability
can be presumed to be high because of the large number of new infections estimated to occur
each year.

Risk Factors

Risk factors for HPV infection are primarily related to sexual behavior, including lifetime and
recent sex partners. Results of epidemiologic studies are less consistent for other risk factors,
including young age at sexual initiation, number of pregnancies, genetic factors, smoking,
and lack of circumcision of male partner.
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Disease Burden in the United States

HPV Disease Burden in the United States

Anogenital HPV is the most common sexually transmitted infection in the US

o estimated 79 million infected
o 14 million new infections/year
Common among adolescents and young adults

Anogenital HPV infection is believed to be the most common sexually transmitted infection
in the United States. An estimated 79 million persons are infected, and an estimated 14
million new HPV infections occur annually with half of these in persons 15-24 years.

The two most common types of cervical cancer worldwide, squamous cell carcinoma
followed by adenocarcinoma, are both caused by HPV. The CDC and National Cancer
Institutes United States Cancer Statistics Working Group reports that from 2005 through
2009 there were annual averages of 12,595 cases and 3,968 deaths due to cervical cancer.
HPV is believed to be responsible for nearly all of these cases of cervical cancer. HPV types
16 and 18 are associated with 70% of these cancers.

In addition to cervical cancer, HPV is believed to be responsible for 90% of anal cancers,
71% of vulvar, vaginal, or penile cancers, and 72% of oropharyngeal cancers.

Population-based estimates, primarily from clinics treating persons with sexually transmitted
infections, indicate that about 1% of the sexually active adolescent and adult population in
the United States have clinically apparent genital warts. More than 90% of cases of
anogenital warts are associated with the low-risk HPV types 6 and 11.

About 8 billion dollars are spent annually on management of sequelae of HPV infections,
primarily for the management of abnormal cervical cytology and treatment of cervical
neoplasia. This exceeds the economic burden of any other sexually transmitted infection
except human immunodeficiency virus.

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Prevention
HPV Infection

HPV transmission can be reduced but not eliminated with the use of physical barriers such as
condoms. Recent studies demonstrated a significant reduction in HPV infection among young
women after initiation of sexual activity when their partners used condoms consistently and
correctly. Abstaining from sexual activity (i.e., refraining from any genital contact with
another individual) is the surest way to prevent genital HPV infection. For those who choose
to be sexually active, a monogamous relationship with an uninfected partner is the strategy
most likely to prevent future genital HPV infections.
Cervical Cancer Screening

Cervical Cancer Screening

Revised in 2012
Screening should begin at age 21 years
Screen women 21 to 65 years of age with Pap test every 3 years
Co-testing (Pap and HPV testing) every 5 years in women 30 to 65 years of age

Most cases and deaths from cervical cancer can be prevented through detection of
precancerous changes within the cervix by cervical cytology using the Pap test. Currently
available Pap test screening can be done by a conventional Pap or a liquid-based cytology.
CDC does not issue recommendations for cervical cancer screening, but various professional
groups have published recommendations. Cervical cancer screening recommendations were
revised in 2012 after the U.S. Preventive Services Task Force (USPSTF) and a
multidisciplinary group, including the American Cancer Society (ASC), American Society
for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical
Pathology (ASCP) reviewed new evidence. Previously, recommendations varied by
organization. Since 2012, all organizations have recommended that screening should begin at
age 21 years. While there are slight differences in other aspects of the recommendations, all
groups recommend screening in women aged 21 to 65 years with cytology (Pap test) every 3
years. For women aged 30 to 65 years who want to lengthen the screening interval, screening
can be done with a combination of cytology and HPV testing (co-testing) every 5 years.

The use of HPV vaccine does not eliminate the need for continued Pap test screening, since
30% of cervical cancers are caused by HPV types not included in the vaccine.

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Human Papillomavirus Vaccine

Human Papillomavirus Vaccine

HPV L1 major capsid protein of the virus is antigen used for immunization
L1 protein produced using recombinant technology
L1 proteins self-assemble into virus-like particles (VLP)
VLP are noninfectious and nononcogeric

Characteristics

Three HPV vaccines are licensed in the United States. The vaccines are non-infectious
subunit vaccines. The antigen for the vaccines is the L1 major capsid protein of HPV,
produced by using recombinant DNA technology. L1 proteins self-assemble into
noninfectious, nononcogenic units called virus-like particles (VLP).

Quadrivalent HPV (HPV4) vaccine (Gardasil, Merck) was approved by the FDA in June
2006. The vaccine is approved for females and males 9 through 26 years of age. Each 0.5-mL
dose of HPV4 contains 20 micrograms HPV 6 L1 protein, 40 micrograms HPV 11 L1
protein, 40 micrograms HPV 16 L1 protein, and 20 micrograms HPV 18 L1 protein. The
vaccine antigen is adsorbed on alum adjuvant. The vaccine also includes sodium chloride, L-
histidine, polysorbate 80, and sodium borate. HPV4 does not contain a preservative or
antibiotic. The vaccine is supplied in single-dose vials and syringes. A 9-valent vaccine
(Merck) was approved by the FDA in December 2014.

HPV Vaccines

HPV4 (Gardasil, Merck)

o approved for females and males 9 through 26 years of age
o contains types 16 and 18 (high risk) and types 6 and 11 (low risk)
a 9-valent vaccine licensed in December 2014
HPV2 (Cervarix, GlaxoSmithKline)
o approved for females 10 through 25 years of age
o contains types 16 and 18 (high risk)

Bivalent HPV (HPV2) vaccine (Cervarix, GlaxoSmithKline) was approved by the FDA in
October 2009. The vaccine is approved for females 9 through 25 years of age. HPV2 is not
approved for males. The L1 antigen is adsorbed onto aluminum hydroxide. The unique
adjuvant system, AS04, is composed of 3-O-desacyl-4-monophosphoryl lipid A (MPL)
adsorbed onto aluminum hydroxide. Each 0.5-mL dose contains 20 micrograms of HPV type
16 L1 protein and 20 micrograms of HPV type 18 L1 protein. HPV2 does not contain a
preservative or antibiotic. It is available in 2 types of prefilled syringes.

Immunogenicity and Vaccine Efficacy

HPV vaccines are highly immunogenic. More than 99% of recipients develop an antibody
response to HPV types included in the respective vaccines 1 month after completing the
three-dose series. However, there is no known serologic correlate of immunity and no known
minimal titer determined to be protective. The high efficacy found in the clinical trials to date
has precluded identification of a minimum protective antibody titer. Further follow-up of
vaccinated cohorts may allow determination of serologic correlates of immunity in the future.

Both HPV vaccines have been found to have high efficacy for prevention of HPV vaccine
typerelated persistent infection, CIN 2/3 and adenocarcinoma in-situ (AIS). Clinical efficacy
for HPV4 against cervical disease was determined in two double-blind, placebo-controlled
trials. In women 16 through 26 years of age vaccine efficacy for HPV 16 or 18related CIN
2/3 or AIS was 97%. HPV4 efficacy against HPV 6, 11, 16 or 18related genital warts was
99%.

HPV2 efficacy was evaluated in two randomized, double-blind, controlled clinical trials in
females aged 15 through 25 years. In the phase III trial, efficacy against HPV 16 or 18-related
CIN 2/3 or AIS was 93%.

HPV4 was evaluated in men 16 through 26 years and found to have 88% efficacy against
vaccine type genital warts. Among men who have sex with men (MSM), efficacy
against anal intraepithelial neoplasia grade 2 or 3 (AIN2/3) was 75%.

HPV Vaccine Efficacy

High efficacy among females without evidence of infection with vaccine HPV types
 No evidence of efficacy against disease caused by vaccine types with which participants
were infected at the time of vaccination
Prior infection with one HPV type did not diminish efficacy of the vaccine against other
vaccine HPV types

Although high efficacy among persons without evidence of infection with vaccine HPV types
was demonstrated in clinical trials of both HPV vaccines, there is no evidence of efficacy
against disease caused by vaccine types with which participants were infected at the time of
vaccination (i.e., the vaccines had no therapeutic effect on existing infection or disease).
Participants infected with one or more vaccine HPV types prior to vaccination were protected
against disease caused by the other vaccine types. Prior infection with one HPV type did not
diminish efficacy of the vaccine against other vaccine HPV types.

The duration of protection following HPV vaccine is not known. For both vaccines a subset
of participants have been followed for more than 60 months with no evidence of waning
protection. Study populations will continue to be followed for any evidence of waning
immunity.

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Vaccination Schedule and Use

ACIP recommends vaccination of females with HPV2 or HPV4 for prevention of cervical
cancers and precancers. HPV4 is recommended also for prevention of genital warts. ACIP
recommends routine vaccination at age 11 or 12 years with HPV4 or HPV2 for females and
with HPV4 for males. The vaccination series can be started beginning at age 9 years.

HPV Vaccination Recommendations

ACIP recommends routine vaccination at age 11 or 12 years with HPV4 or HPV2 for females
and HPV 4 for males
The vaccination series can be started as young as 9 years of age
Vaccination also recommended for females 13 through 26 years of age
Vaccination also recommended for males 13 through 21 years of age
All immunocompromised males (including HIV infection) and MSM through 26 years of age
should be vaccinated
Males aged 22 through 26 years may be vaccinated

HPV4 and HPV2 are each administered in a 3-dose series. The second dose should be
administered 1 to 2 months after the first dose and the third dose 6 months after the first dose.
Vaccination also is recommended for females aged 13 through 26 years and for males aged
13 through 21 years, who have not been previously vaccinated or who have not completed the
3-dose series. For immunocompromised males (including HIV infection) and men who have
sex with men, ACIP recommends routine vaccination with HPV4, as for all males, through
26 years of age for those who have not been vaccinated previously or who have not
completed the 3-dose series. Males aged 22 through 26 years without these risk factors may
be vaccinated as well. HPV2 is neither licensed nor recommended for males.
If females or males reach age 27 years before the vaccination series is complete, the second
and/or third doses of vaccine can be administered after age 26 to complete the vaccination
series.

Prevaccination assessments (e.g., Pap testing or screening for high-risk HPV DNA, type-
specific HPV tests, or HPV antibody) to establish the appropriateness of HPV vaccination are
not recommended.

Ideally, vaccine should be administered before potential exposure to HPV through sexual
contact; however, persons who may have already been exposed to HPV should be vaccinated.
Sexually active persons who have not been infected with any of the HPV vaccine types will
receive full benefit from vaccination. Vaccination will provide less benefit to persons if they
have already been infected with one or more of the HPV vaccine 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 of HPV infection may continue as long as persons are sexually
active. Pap testing or screening for HPV DNA or HPV antibody is not recommended prior to
vaccination at any age.

Both HPV vaccines are administered in a three-dose series of intramuscular injections. The
second and third doses should be administered 1 to 2 and 6 months after the first dose. The
third dose should follow the first dose by at least 24 weeks. The third dose need not be
repeated as long as it was administered at least 16 weeks after the first dose and at least 12
weeks after the second dose. An accelerated schedule for HPV vaccine is not recommended.

HPV Vaccination Schedule

Routine schedule is 0, 1 to 2, 6 months

An accelerated schedule using minimum intervals is not recommended
Series does not need to be restarted if the schedule is interrupted
Prevaccination assessments not recommended
No therapeutic effect on HPV infection, genital warts, cervical lesions

There is no maximum interval between doses. If the 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 given 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.

Whenever feasible, the same HPV vaccine should be used for the entire vaccination series.
No studies address interchangeability of HPV vaccines. However, if the vaccine provider
does not know or have available the HPV vaccine product previously administered, either
HPV vaccine can be used to complete the series to provide protection against HPV 16 and 18.
For protection against HPV 6 or 11-related genital warts, a vaccination series with fewer than
3 doses of HPV4 might provide less protection than a complete 3-dose HPV4 series.

HPV vaccine should be administered at the same visit as other age-appropriate vaccines, such
as Tdap and quadrivalent meningococcal conjugate (MCV4) vaccines. Administering all
indicated vaccines 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.
As mentioned, prevaccination assessments (e.g. Pap testing or screening for high-risk HPV
DNA, type-specific HPV tests, or HPV antibody) to establish the appropriateness of HPV
vaccination are not recommended at any age. HPV vaccination can provide protection
against infection with HPV vaccine types not already acquired. Therefore, vaccination is
recommended through the recommended age for females regardless of whether they have an
abnormal pap test result, and for females or males regardless of known HPV infection.

Women should be advised that the vaccine will not have a therapeutic effect on existing HPV
infection, genital warts or cervical lesions.

A history of genital warts or clinically evident genital warts indicates infection with HPV,
most often type 6 or 11. However, these persons may be infected with HPV types other than
the HPV4 vaccine types, and therefore they may receive HPV4 vaccine if they are in the
recommended age group. Persons with a history of genital warts should be advised that data
do not indicate HPV4 vaccine will have any therapeutic effect on existing HPV infection or
genital warts.

Because HPV vaccines are subunit vaccines, they can be administered to persons who are
immunosuppressed because of disease or medications. However, the immune response and
vaccine efficacy might be less than that in persons who are immunocompetent. Women who
are breastfeeding may receive HPV vaccine.

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Contraindications and Precautions to Vaccination

HPV Vaccine Contraindication and Precautions

Contraindication
o severe allergic reaction to a vaccine component or following a prior dose
Precaution
o moderate or severe acute illnesses (defer until symptoms improve)

A severe allergic reaction (e.g., anaphylaxis) to a vaccine component or following a prior

dose of HPV vaccine is a contraindication to receipt of HPV vaccine. Anaphylactic allergy to
latex is a contraindication to bivalent HPV vaccine in a prefilled syringe since the tip cap
contains natural rubber latex. A moderate or severe acute illness is a precaution to
vaccination, and vaccination should be deferred until symptoms of the acute illness improve.
A minor acute illness (e.g., diarrhea or mild upper respiratory tract infection, with or without
fever) is not a reason to defer vaccination.

HPV vaccine is not recommended for use during pregnancy. The vaccine has not been
causally associated with adverse pregnancy outcomes or with adverse effects on the
developing fetus, but data on vaccination during pregnancy are limited. Pregnancy testing
before vaccination is not needed. However, if a woman is found to be pregnant after initiation
of the vaccination series, the remainder of the series should be delayed until after completion
of the pregnancy. No intervention is indicated. Women known to be pregnant should delay
initiation of the vaccine series until after delivery.
HPV Vaccination During Pregnancy

Initiation of the vaccine series should be delayed until after completion of pregnancy
If a woman is found to be pregnant after initiating the vaccination series, remaining doses
should be delayed until after the pregnancy
If a vaccine dose has been administered during pregnancy, there is no indication for
intervention
Women vaccinated during pregnancy should be reported to the respective manufacturer

HPV Vaccine Adverse Reactions

Local reactions (pain, redness, swelling)

o 20%-90%
Fever (100F)
o 10%-13%*
No serious adverse reactions associated with either vaccine

*similar to reports in placebo recipients

Pregnancy registries for both HPV2 and HPV4 have been terminated. However, vaccination
with either vaccine during pregnancy may still be reported to VAERS or to the manufacturer:
GlaxoSmithKline at 1-888-825-5249 (for HPV2), or Merck at 1-877-888-4231 (for HPV4).

Adverse Reactions Following Vaccination

The most common adverse reactions reported during clinical trials of HPV vaccines were
local reactions at the site of injection. In prelicensure clinical trials, local reactions, such as
pain, redness or swelling were reported by 20% to 90% of recipients. A temperature of 100F
during the 15 days after vaccination was reported in 10% to 13% of recipients of either
vaccine. A similar proportion of placebo recipients reported an elevated temperature. Local
reactions generally increased in frequency with increasing doses. However, reports of fever
did not increase significantly with increasing doses. No serious adverse events have been
associated with either HPV vaccine based on monitoring by CDC and the Food and Drug
Administration.

A variety of systemic adverse reactions were reported by vaccine recipients, including

nausea, dizziness, myalgia and malaise. However, these symptoms occurred with equal
frequency among both vaccine and placebo recipients.

Syncope has been reported among adolescents who received HPV and other vaccines
recommended for this age group (Tdap, MCV4). Recipients should always be seated during
vaccine administration. Clinicians should consider observing recipient for 15 minutes after
vaccination.

Vaccine Storage and Handling

HPV vaccines should be maintained at refrigerator temperature between 35F and 46F (2C
and 8C). Manufacturer package inserts contain additional information. For complete
information on best practices and recommendations please refer to CDCs Vaccine Storage
and Handling Toolkit[4.33 MB, 109 pages].

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Acknowledgment

The editors thank Drs. Lauri Markowitz and Elizabeth Unger for their assistance in updating
this chapter.

Selected References

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ACOG committee opinion No. 467. Obstet Gynecol 2010;116:800803.
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Committee on Immunization Practices (ACIP). MMWR 2007;56(No.RR-2):124.
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https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html
http://www.arhp.org/Publications-and-Resources/Patient-Resources/Fact-Sheets/Understanding-
HPV-Vaccine