Human Papillomavirus

Elissa Meites, MD, MPH; Julianne Gee, MPH; Elizabeth Unger, PhD, MD; and Lauri Markowitz, MD
Human papillomavirus (HPV) is the most common sexually
transmitted infection in the United States. Although the
majority of HPV infections are asymptomatic and resolve
spontaneously, persistent infections can develop into
anogenital warts, precancers, and cervical, anogenital, or
oropharyngeal cancers in women and men. The relationship
between 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 shown to contain HPV DNA. Epidemiologic studies
demonstrating a consistent association between HPV and
cervical cancer were published in the 1990s; more recently,
HPV has been identified as a cause of certain other mucosal
cancers. A quadrivalent vaccine to prevent infection with four
types of HPV was licensed for use in the United States in 2006,
a bivalent vaccine was licensed in 2009, and a 9-valent vaccine
was licensed in 2014.
11
Human Papillomaviruses Human Papillomaviruses (HPV)
HPV consists of a family of small, double-stranded DNA viruses ● Small DNA virus
that infect the epithelium. More than 200 distinct types have ● More than 200 types have been
been identified; they are differentiated by their genomic identified
sequence. Most HPV types infect the cutaneous epithelium ● Most HPV types infect the
and can cause common skin warts. About 40 types infect the
cutaneous epithelium and can
mucosal epithelium; these are categorized according to their
cause common skin warts
epidemiologic association with cervical cancer.
● About 40 types infect the
Infection with low-risk or nononcogenic types, such as types 6 mucosal epithelium
or 11, can cause benign or low-grade cervical cell abnormalities,
anogenital warts, and respiratory tract papillomas. More than Human Papillomavirus Types
90% of cases of anogenital warts are caused by low-risk HPV and Disease Association
types 6 or 11.

High-risk or oncogenic HPV types act as carcinogens in the

development of cervical cancer and other anogenital cancers.
High-risk types (including types 16, 18, and 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
precancers. Type 16 is the cause of approximately 50% of cervical
cancers worldwide, and types 16 and 18 together account for
about 66% of cervical cancers. An additional five high-risk types,
31, 33, 45, 52, and 58, are responsible for another 15% of cervical
cancers and 11% of all HPV-associated cancers. Infection with a
high-risk HPV type is considered necessary for the development
of cervical cancer but, by itself, is not sufficient to cause cancer.
The vast majority of women with HPV infection, even those with
high-risk HPV types, do not develop cancer.

In addition to cervical cancer, high-risk HPV infection is

associated with less common anogenital cancers, such as cancer
of the vulva, vagina, penis, and anus. These HPV types can also
cause oropharyngeal cancers.
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 Human Papillomavirus
Pathogenesis
Pathogenesis of HPV Infection
and Cervical Cancer HPV infection occurs at the basal epithelium. Although
incidence of infection is high, most infections resolve
spontaneously within a year or two. A small proportion of
infected persons become persistently infected; persistent
infection is the most important risk factor for the development
of cervical cancer.

In women, squamous intraepithelial lesions (SIL) of the cervix

can be detected through screening. Low-grade squamous
intraepithelial lesions (LSIL) often regress. High-grade
squamous intraepithelial lesions (HSIL) are considered cancer
precursors. Previously, these types of cervical lesions were
called cervical intraepithelial neoplasia (CIN). If left undetected
and untreated, such cancer precursors can progress to cervical
cancer years or decades later.

The pathogenesis of other types of HPV-related cancers may

11 follow a similar course, although less is known about their
respective precursor lesions: anal HSIL has been identified as
a precursor to anal cancer, vulvar HSIL has been identified as a
precursor to vulvar cancer, and vaginal HSIL has been identified
as a precursor to vaginal cancer.

Infection with one type of HPV does not prevent infection

with another type. Of persons infected with HPV that infects
the mucosal epithelium, 5% to 30% are infected with multiple
types of the virus.

HPV Clinical Features

Clinical Features
Most HPV infections are asymptomatic and result in no clinical
● Most HPV infections are
disease. Clinical manifestations of HPV infection include
asymptomatic and result in no
anogenital warts, recurrent respiratory papillomatosis, cervical
clinical disease
cancer precursors (cervical intraepithelial neoplasia), and
● Clinical manifestations of cancers, including cervical, anal, vaginal, vulvar, penile, and
HPV infection include: oropharyngeal cancer.
■ Anogenital warts
■ Recurrent respiratory Laboratory Testing
papillomatosis HPV is not cultured by conventional methods. Infection is
identified by detection of HPV DNA from clinical specimens.
■ Cervical cancer precursors
Assays for HPV detection differ considerably in their
(HSIL)
sensitivity and type specificity, and detection is also affected
■ Cancer (cervical, anal, by the anatomic region sampled, as well as the method of
vaginal, vulvar, penile, and specimen collection.
oropharyngeal cancer)
Several HPV tests have been approved by the Food and Drug
Administration (FDA) and detect up to 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 when the presence of any combination
of these HPV types is detected; certain tests specifically identify
HPV types 16 and/or 18. These tests are approved for use in
women as part of cervical cancer screening either as primary

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screen, co-test with cytology, or management of abnormal
cervical cytology results on a Papanicolaou (Pap) test. HPV tests
are neither 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. Serology results are not used clinically.

Medical Management
No specific treatment is required or recommended for
asymptomatic HPV infection. Medical management is
recommended for treatment of specific clinical manifestations
11
of HPV-related disease (e.g., anogenital warts, precancerous
lesions, or cancers).

Epidemiology HPV Epidemiology

Occurrence ● Reservoir
HPV infection is extremely common throughout the world. ■ Human
Most sexually active adults will have an HPV infection at ● Transmission
some point during their lives, although they may be unaware
of their infection.
■ Direct contact, usually sexual
● Temporal pattern
Reservoir ■ None
Humans are the only natural reservoir for HPV. Other viruses in ● Communicability
the papillomavirus family affect other species.
■ Presumed to be high

Transmission ● Risk factors

HPV is transmitted through intimate, skin-to-skin contact with ■ Sexual behavior, including
an infected person. Transmission is most common during higher number of lifetime and
vaginal, penile, anal, or oral sex. recent sex partners

Studies of newly acquired HPV infection demonstrate that

infection typically occurs soon after first sexual activity. In a
prospective study of college women, the cumulative incidence
of infection was 40% by 24 months after first sexual intercourse,
and 10% of infections were caused by HPV 16.

Autoinoculation from one body site to another can occur.

Very rarely, vertical transmission of HPV from an infected mother

to her infant can result in a condition called juvenile-onset
recurrent respiratory papillomatosis.

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Temporal Pattern
There is no known seasonal variation in HPV infection.

Communicability
HPV is presumed to be communicable during both acute and
persistent infections. Communicability can be presumed 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 higher numbers of lifetime and recent sex
partners. Results of epidemiologic studies are less consistent
for other risk factors, including younger age at sexual initiation,
higher number of pregnancies, genetic factors, smoking, and
lack of circumcision of the male partner.

11 Secular Trends in the United States

HPV Secular Trends in
the United States Genital HPV infection is the most common sexually transmitted
infection in the United States and worldwide.
● Genital HPV is the most
common sexually transmitted Based on data from 2003-2006 (before vaccine introduction), an
infection in the U.S. estimated 79 million persons were infected in the United States.
● Common among adolescents Approximately 14 million new HPV infections occurred annually,
and young adults with nearly half occurring in persons age 15 through 24 years.
● Before vaccine introduction During 2013–2014, genital prevalence of any of 37 HPV types
assayed was 45.2% and prevalence of high-risk HPV types was
■ Estimated 79 million infected 25.1% among U.S. men age 18 through 59 years. Also during
■ 14 million new infections/year this period, genital prevalence of any of 37 HPV types assayed
● Within 10 years following was 39.9% and prevalence of high-risk HPV types was 20.4%
vaccine introduction, among U.S. women in the same age range. Within a decade
prevalence of HPV types 6, 11, following the U.S. introduction of quadrivalent HPV vaccine in
16, and 18 has decreased: 2006, prevalence of HPV types 6, 11, 16, and 18 decreased 86%
among females age 14 through 19 years and decreased 71%
■ 86% among females age among females age 20 through 24 years.
14 through 19 years
■ 71% among females age The National Cancer Institute’s (NCI) Surveillance, Epidemiology,
20 through 24 years and End Results (SEER) program and CDC’s National Program of
Cancer Registries provide data on the number of HPV cancers in
the United States. On average, 43,999 HPV-associated cancers
are reported annually, including 24,886 in females and 19,113 in
males. By gender, the most common cancers attributed to HPV
are an estimated 10,900 cervical cancers in women and 11,300
oropharyngeal cancers in men.

In addition to 91% of cervical cancer, HPV is responsible

for about 91% of anal cancers, 69% of vulvar cancers, 75%
of vaginal cancers, 63% of penile cancers, and 70% of
oropharyngeal cancers.

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On the basis of health claims data in the United States,
the incidence of anogenital warts in 2004 (before vaccine
introduction) was 1.2 per 1,000 females and 1.1 per 1,000 males.
During 2003–2010, reductions in anogenital wart prevalence
were observed among U.S. females age 15 through 24 years, the
group most likely to be affected by introduction of HPV vaccine.
By 2014, decreasing prevalence of anogenital warts was also
identified in young men.

From 2008–2015, both CIN grade 2 or worse (CIN2+) rates

and cervical cancer screening declined among women age 18
through 24 years. Significant decreases in CIN2+ rates among
screened women in this age group were consistent with
population-level impact of HPV vaccination.

Among adolescents age 13 through 17 years in 2019, 71.5%

had received at least 1 dose of HPV vaccine, and 54.2% were
up-to-date with HPV vaccination (including adolescents who
received an HPV vaccine series of 2 doses initiated before age
15 years, or else 3 doses, at the recommended intervals). Among 11
females, 73.2% had received at least 1 dose of HPV vaccine and
56.8% were up-to-date with HPV vaccination. Among males,
69.8% had received at least 1 dose of HPV vaccine and 51.8%
were up-to-date with HPV vaccination. Each of these coverage
estimates represents a statistically significant increase in HPV
vaccination coverage from 2018.

Prevention
Vaccination prevents HPV infection, benefitting both the
vaccinated person and their future sex partners by preventing Cervical Cancer Screening
spread of HPV. HPV transmission can be reduced, but not
● Annual cervical cancer
eliminated, with the consistent and correct use of physical
screening not recommended
barriers such as condoms.
for average-risk individuals

Cervical Cancer Screening ● For ages 21 through 29 years,

screen with cytology testing
Most cases of and deaths from cervical cancer can be prevented
every 3 years
through screening and treatment. The Pap test detects
precancerous changes in cervical cells collected by a health ● For ages 30 through 65 years,
care provider and placed on a slide (a conventional Pap) or in screen with choice of cytology
liquid media (liquid-based cytology). Clinical tests for HPV can test every 3 years, an HPV test
be used as a primary screen either alone or in combination with alone every 5 years, or cytology
cytology (co-test) or as triage after an equivocal cytology result. test plus HPV test every 5 years
● USPSTF and ACOG have similar
Recommendations for cervical cancer screening in the United screening recommendations;
States are based on systematic evidence reviews by major ACS recommends that
medical and other organizations including the U.S. Preventive screening start at age 25 years
Services Task Force (USPSTF), American Cancer Society (ACS), for average-risk persons
and the American College of Obstetricians and Gynecologists
(ACOG). Annual cervical cancer screening is not recommended ● HPV vaccination does not
for average-risk individuals. Instead, cytology testing is eliminate the need for cervical
cancer screening

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recommended every 3 years from age 21 through 29 years.
Between age 30 and 65 years, a choice of a cytology test every
3 years, an HPV test alone every 5 years, or cytology test plus an
HPV test (co-test) every 5 years is recommended. Co-testing can
be done by either collecting one sample for the cytology test
and another for the HPV test or by using the remaining liquid
cytology material for the HPV test. Cervical screening programs
should screen those who have received HPV vaccination in the
same manner as those who are unvaccinated. Screening is not
recommended before age 21 years in those at average risk. For
those age 30 to 65 years, cytology alone or primary HPV testing
are preferred by USPSTF, but co-testing can be used as an
alternative approach. USPSTF and ACOG have similar screening
recommendations. ACS recommends that screening start at age
25 years for average-risk persons.

HPV Vaccines HPV vaccination does not eliminate the need for continued
cervical cancer screening, since up to 30% of cervical cancers
● 9vHPV (Gardasil 9) is licensed
are caused by HPV types not prevented by the quadrivalent or
11 and currently distributed in
bivalent vaccines, and 15% of cervical cancers are caused by
the U.S.
HPV types not prevented by the 9-valent vaccine.
■ Prevents HPV types 6, 11,
16, 18, 31, 33, 45, 52, 58
● 4vHPV and 2vHPV are licensed Human Papillomavirus Vaccines
but not currently distributed in A 9-valent recombinant protein subunit HPV vaccine (9vHPV,
the U.S. Gardasil 9) is licensed for use and is currently distributed in the
United States. Two additional HPV vaccines remain licensed
■ 4vHPV prevents HPV types 6,
in the United States but are not currently distributed: a
11, 16, 18
quadrivalent HPV vaccine (4vHPV, Gardasil), and a bivalent HPV
■ 2vHPV prevents HPV types vaccine (2vHPV, Cervarix). All of the vaccines prevent infection
16, 18 with high-risk HPV types 16 and 18, types that cause most
cervical and other cancers attributable to HPV; 9vHPV vaccine
also prevents infection with five additional high-risk types. In
HPV Vaccine Characteristics addition, 4vHPV and 9vHPV vaccines prevent infections with
● HPV L1 major capsid protein HPV types 6 and 11, types that cause anogenital warts.
of the virus is antigen used for
immunization Characteristics
● L1 protein produced using The antigen for HPV vaccines is the L1 major capsid protein
recombinant technology of HPV, produced by using recombinant DNA technology. L1
proteins self-assemble into noninfectious, nononcogenic units
● L1 proteins self-assemble into
called virus-like particles (VLPs). The L1 proteins are produced
virus-like particles (VLP)
by fermentation using Saccharomyces cerevisiae yeast; 9vHPV
● VLPs are noninfectious and vaccine contains yeast protein. 9vHPV vaccine contains VLPs
nononcogenic for nine HPV types: two types that cause anogenital warts
● Administer by intramuscular (HPV types 6 and 11) and seven types that can cause cancers
injection (HPV types 16, 18, 31, 33, 45, 52, and 58). 9vHPV vaccine is
administered by intramuscular injection. Each dose of 9vHPV
● 9vHPV contains yeast protein
vaccine contains aluminum as an adjuvant. It contains no
● 9vHPV contains aluminum antibiotic or preservative.
adjuvant

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Vaccination Schedule and Use
HPV Vaccination Schedule
HPV vaccination is recommended for females and males
at age 11 or 12 years for prevention of HPV infections and
● Routine vaccination
HPV-associated diseases, including certain cancers. The recommended for females and
vaccination series can be started at age 9 years. Catch-up males at age 11 or 12 years
HPV vaccination is recommended for all persons through age (minimum age 9 years)
26 years who are not adequately vaccinated. Catch-up HPV ● Catch-up vaccination
vaccination is not recommended for all adults older than age recommended for all persons
26 years, since the public health benefit of vaccination in this not adequately vaccinated
age range is minimal. HPV vaccines are not licensed for use in through age 26 years
persons older than age 45 years. ● Catch-up vaccination not
recommended for all adults
HPV vaccines are administered as a 2- or 3-dose series,
over age 26 years
depending on age at initiation and medical conditions.
● Shared clinical decision-making
A 2-dose series is recommended for persons who receive the is recommended for some
first valid dose before their 15th birthday (except for persons adults age 27 through 45 years
with certain immunocompromising conditions). The second and ● Not licensed for adults over
final dose should be administered 6 through 12 months after
the first dose (0, 6–12 month schedule). If dose 2 is administered
age 45 11
at least 5 months after the first dose, it can be counted as valid.
If dose 2 is administered at a shorter interval, an additional dose
should be administered at least 12 weeks after dose 2 and at HPV Vaccination Schedule
least 6 to 12 months after dose 1. ● 2-dose series
A 3-dose series is recommended for persons who receive the ■ For immunocompetent
first valid dose on or after their 15th birthday, and for persons persons who receive first valid
with primary or secondary immunocompromising conditions dose before 15th birthday
that might reduce cell-mediated or humoral immunity, such as ■ 0, 6–12 month schedule
B lymphocyte antibody deficiencies, T lymphocyte complete or ■ Minimum interval of
partial defects, human immunodeficiency virus (HIV) infection,
5 months
malignant neoplasm, transplantation, autoimmune disease, or
immunosuppressive therapy, in whom immune response to ● 3-dose series
vaccination may be attenuated. In a 3-dose schedule, dose 2 ■ For persons who receive
should be administered 1–2 months after dose 1, and dose 3 first valid dose on or after
should be administered 6 months after dose 1 (0, 1–2, 6 month 15th birthday
schedule).
■ For persons with
There is no maximum interval between doses. If the HPV primary or secondary
vaccination schedule is interrupted, the vaccine series does immunocompromising
not need to be restarted. For persons who already received 1 conditions
dose of HPV vaccine before their 15th birthday, and now are ■ 0, 1–2, 6 month schedule
age 15 years or older, the 2-dose series is considered adequate. ● Series does not need to be
If the series was interrupted after dose 1, dose 2 should be restarted if the schedule
administered as soon as possible. is interrupted
Routine HPV vaccination is recommended beginning at 9 years ● Prevaccination assessments
of age for children with any history of sexual abuse or assault. not recommended
● No therapeutic effect on
Ideally, vaccine should be administered before any exposure existing HPV infection,
to HPV through sexual contact. However, persons in the anogenital warts, or
HPV-related lesions

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routine and catch-up age ranges (through age 26 years)
should be vaccinated, even if they might have been exposed
to HPV in the past.

Vaccination will provide less benefit to sexually active persons

who have been already infected with one or more HPV vaccine
types. However, HPV vaccination can provide protection against
HPV vaccine types not already acquired. Recipients may be
advised that prophylactic vaccine is not expected to have a
therapeutic effect on existing HPV infection, anogenital warts,
or HPV-related lesions.

HPV vaccine should be administered at the same visit as other

age-appropriate vaccines, such as Tdap and quadrivalent
meningococcal conjugate (MenACWY) vaccines. Administering
all indicated vaccines at a single visit increases the likelihood
that patients will receive each of the vaccines on schedule. Each
vaccine should be administered using a separate syringe at a
different anatomic site.
11
Catch-up vaccination is recommended through age 26 years.
Above this age, shared clinical decision-making regarding HPV
vaccination is recommended for some adults age 27 through 45
years who are not adequately vaccinated. HPV vaccination does
not need to be discussed with most adults over age 26 years;
clinicians can consider discussing HPV vaccination with persons
who are most likely to benefit.

Considerations for shared clinical decision-making regarding

HPV vaccination of adults age 27 through 45 years include:

• HPV is a very common sexually transmitted infection. Most

HPV infections are transient and asymptomatic and cause
no clinical problems.

• Although new HPV infections are most commonly

acquired in adolescence and young adulthood, some
adults are at risk for acquiring new HPV infections. At any
age, having a new sex partner is a risk factor for acquiring a
new HPV infection.

• Persons who are in a long-term, mutually monogamous

sexual partnership are not likely to acquire a new
HPV infection.

• Most sexually active adults have been exposed to some

HPV types, although not necessarily to all of the HPV types
targeted by vaccination.

• No clinical antibody test can determine whether a person is

already immune or still susceptible to any given HPV type.

• HPV vaccine efficacy is high among persons who have not

been exposed to vaccine-type HPV before vaccination.

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• Vaccine effectiveness might be low among persons with
risk factors for HPV infection or disease (e.g., adults with
multiple lifetime sex partners and likely previous infection
with vaccine-type HPV), as well as among persons with
certain immunocompromising conditions.

• HPV vaccines are prophylactic (i.e., they prevent new

HPV infections). They do not prevent progression of HPV
infection to disease, decrease time to clearance of HPV
infection, or treat HPV-related disease.

Prevaccination assessments (e.g., HPV testing of any kind,

cervical cancer screening or Pap testing, pregnancy testing, or
“virginity testing”) are not required. No prevaccination testing
(e.g., Pap or HPV testing) is recommended to establish the
appropriateness of HPV vaccination.

The Advisory Committee on Immunization Practices (ACIP)

has not preferentially recommended any of the licensed HPV
vaccines. There is no ACIP recommendation for additional 11
vaccination with 9vHPV for persons who have completed a
series with one of the other recommended HPV vaccines.

Vaccine recipients should always be seated during vaccine

administration. Because syncope has sometimes been reported
in association with HPV vaccination, clinicians should consider
observing recipients for 15 minutes after vaccination.

Immunogenicity and Vaccine Efficacy

HPV Vaccine Efficacy
HPV vaccine is highly immunogenic. More than 98% of
● High vaccine efficacy
recipients develop an antibody response to each covered HPV
type within one month after completing the vaccine series. ● More than 98% of recipients
However, there is no known serologic correlate of protection develop an antibody response
and the minimum antibody titer needed for protection has not to covered HPV types within
been determined. The high efficacy found in the clinical trials one month after completing
has precluded identification of this threshold. Further follow-up the series
of vaccinated cohorts might allow determination of serologic ● No evidence of efficacy against
correlates of protection in the future. disease caused by vaccine
types with which participants
All licensed HPV vaccines have high efficacy for prevention
were infected at the time of
of HPV vaccine-type-related persistent infection, CIN2+, and
vaccination
adenocarcinoma in-situ (AIS). Prelicensure, clinical efficacy for
4vHPV was assessed in phase III clinical trials. To date, ongoing ● Prior infection with one HPV
monitoring has demonstrated that vaccine effectiveness type did not diminish efficacy
remains above 90%, with no waning of immunity through at of the vaccine against other
least 10 to 12 years after immunization. vaccine HPV types

Although high efficacy was demonstrated among persons

without evidence of prior infection with HPV vaccine types
in clinical trials, there was no evidence of efficacy against
disease caused by vaccine types with which participants were
already infected at the time of vaccination (i.e., the vaccines
had no therapeutic effect on existing infection or disease).

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Participants infected with one or more HPV vaccine types prior
to vaccination were protected against disease caused by the
other vaccine types. Prior infection with one HPV type did not
diminish vaccine efficacy against other HPV vaccine types.

Contraindications and Precautions

HPV Vaccine Contraindications to Vaccination
and Precautions As with other vaccines, a history of a severe allergic reaction
● Contraindication (anaphylaxis) to a vaccine component or following a prior
dose is a contraindication to further doses. Moderate or severe
■ Severe allergic reaction to
acute illness (with or without fever) in a patient is considered a
a vaccine component or
precaution to vaccination, although persons with minor illness
following a prior dose
may be vaccinated.
■ History of immediate
hypersensitivity to yeast Both 4vHPV and 9vHPV are produced using Saccharomyces
(4vHPV and 9vHPV only) cerevisiae (baker’s yeast) and thus are contraindicated for
persons with a history of immediate hypersensitivity to yeast.
Anaphylactic allergy to latex
11
■

2vHPV should not be used in persons with an anaphylactic

(2vHPV only)
allergy to latex as the pre-filled syringes might contain latex in
● Precaution the tip cap.
■ Moderate or severe acute
illnesses (defer until Vaccination during Pregnancy
symptoms improve) HPV vaccines are not recommended for use during pregnancy.
If a person is found to be pregnant after starting the vaccine
series, the remainder of the series should be delayed until after
HPV Vaccination During Pregnancy pregnancy. If a vaccine dose has been administered during
● Initiation of the vaccine series pregnancy, no intervention is needed. Pregnancy testing is not
should be delayed until after needed before vaccination.
completion of pregnancy
A pregnancy registry has been established by the manufacturer
● If a woman is found to be of 9vHPV. Women exposed to this vaccine around the time
pregnant after initiating the of conception or during pregnancy are encouraged to be
vaccination series, remaining registered by calling 1-800-986-8999 (merckpregnancyregistries.
dose(s) should be delayed until com/gardasil9.html).
after the pregnancy
● If a vaccine dose has been Persons who are lactating or breastfeeding can receive
administered during pregnancy, HPV vaccine.
there is no indication for
intervention
Vaccine Safety
● Women vaccinated during HPV vaccine is generally well-tolerated. Safety has been
pregnancy should be reported well-established from prelicensure trials and postlicensure
to the manufacturer monitoring and evaluation.
● Pregnancy testing is not
needed before 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 100°F during the 15 days after

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 Human Papillomavirus
vaccination was reported by 10% to 13% of HPV vaccine
recipients. A similar proportion of placebo recipients reported HPV Vaccine Safety
an elevated temperature. Local reactions generally increased in ● HPV vaccine is generally well-
frequency with increasing doses. However, reports of fever did tolerated
not increase significantly with increasing doses. Although rare, ● Local reactions (pain, redness,
anaphylaxis can occur. No other serious adverse events have swelling)
been significantly associated with any HPV vaccine, based on
monitoring by CDC and FDA. ■ 20%-90%
● Fever (100%)
A variety of systemic adverse events following vaccination were
■ 10%-13% (similar to reports in
reported by vaccine recipients, including nausea, dizziness,
placebo recipients)
myalgia, and malaise. However, these symptoms occurred with
similar frequency among vaccine and placebo recipients. ● Anaphylaxis is rare, but can
occur
Postlicensure monitoring of reports from the Vaccine ● No other serious adverse
Adverse Event Reporting System (VAERS) did not identify any
reactions associated with any
unexpected adverse event, was consistent with data from
HPV vaccine
prelicensure clinical trials, and supports the safety data for
9vHPV. The Vaccine Safety Datalink did not identify any new
safety concerns after monitoring around 839,000 doses of 11
9vHPV administered during 2015–2017.

Because syncope has sometimes been reported, vaccine

recipients should always be seated during vaccine
administration. Clinicians should consider observing recipients
for 15 minutes after vaccination.

Vaccine Storage and Handling

HPV vaccines should be maintained at refrigerator temperature
between 2°C and 8°C (36°F and 46°F). Manufacturer package
inserts contain additional information. For complete information
on best practices and recommendations for vaccine storage and
handling, please refer to CDC’s Vaccine Storage and Handling
Toolkit, www.cdc.gov/vaccines/hcp/admin/storage/toolkit/
storage-handling-toolkit.pdf.

Surveillance and Reporting of HPV Infection

HPV infection is not a nationally notifiable condition. For
information on guidance for state and local health department
staff who are involved in surveillance activities for vaccine-
preventable diseases, please consult the Manual for the
Surveillance of Vaccine-Preventable Diseases, www.cdc.gov/
vaccines/pubs/surv-manual/chapters.html.

Acknowledgements
The editors would like to acknowledge Valerie Morelli,
Ginger Redmon, and Mona Saraiya for their contributions to
this chapter.

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 Human Papillomavirus
Selected References
NOTES CDC. Human papillomavirus vaccination for adults: updated
recommendations of the Advisory Committee on Immunization
Practices. MMWR 2019;68(32):698–702.

CDC. Human papillomavirus vaccination: recommendations

of the Advisory Committee on Immunization Practices (ACIP).
MMWR 2014;63(RR-05):1–30.

CDC. Use of a 2-dose schedule for human papillomavirus

vaccination—updated recommendations of the
Advisory Committee on Immunization Practices. MMWR
2016;65(49):1405–8.

CDC. Use of 9-valent human papillomavirus (HPV) vaccine:

updated HPV vaccination recommendations of the
Advisory Committee on Immunization Practices. MMWR
2015;64(11):300–4.
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