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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.

Human Papillomaviruses

HPV consists of a family of small, double-stranded DNA viruses 

that infect the epithelium. More than 200 distinct types have 

been identified; they are differentiated by their genomic 

sequence. 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 

or 11, can cause benign or low-grade cervical cell abnormalities, 

anogenital warts, and respiratory tract papillomas. More than 

90% of cases of anogenital warts are caused by low-risk HPV 

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.

Elissa Meites, MD, MPH; Julianne Gee, MPH; Elizabeth Unger, PhD, MD; and Lauri Markowitz, MD

Human Papillomaviruses (HPV)

● Small DNA virus

● More than 200 types have been

identified

● Most HPV types infect the

cutaneous epithelium and can

cause common skin warts

● About 40 types infect the

mucosal epithelium

Human Papillomavirus Types

and Disease Association

https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html Aug 2021
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Pathogenesis of HPV Infection 

and Cervical Cancer

Pathogenesis

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 

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.

Clinical Features

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 Testing

HPV is not cultured by conventional methods. Infection is 

identified by detection of HPV DNA from clinical specimens. 

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 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 

HPV Clinical Features

● 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

(HSIL)

■ Cancer (cervical, anal,

vaginal, vulvar, penile, and

oropharyngeal cancer)
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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 viruslike-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 

of HPV-related disease (e.g., anogenital warts, precancerous 

lesions, or cancers).

Epidemiology

Occurrence

HPV infection is extremely common throughout the world. 

Most sexually active adults will have an HPV infection at 

some point during their lives, although they may be unaware 

of their infection. 

Reservoir

Humans are the only natural reservoir for HPV. Other viruses in 

the papillomavirus family affect other species. 

Transmission

HPV is transmitted through intimate, skin-to-skin contact with 

an infected person. Transmission is most common during 

vaginal, penile, anal, or oral sex. 

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. 

HPV Epidemiology

● Reservoir

■ Human

● Transmission

■ Direct contact, usually sexual

● Temporal pattern

■ None

● Communicability

■ Presumed to be high

● Risk factors

■ Sexual behavior, including 

higher number of lifetime and 

recent sex partners
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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.

Secular Trends in the United States

Genital HPV infection is the most common sexually transmitted 

infection in the United States and worldwide. 

Based on data from 2003-2006 (before vaccine introduction), an 

estimated 79 million persons were infected in the United States. 

Approximately 14 million new HPV infections occurred annually, 

with nearly half occurring in persons age 15 through 24 years. 

During 2013–2014, genital prevalence of any of 37 HPV types 

assayed was 45.2% and prevalence of high-risk HPV types was 

25.1% among U.S. men age 18 through 59 years. Also during 

this period, genital prevalence of any of 37 HPV types assayed 

was 39.9% and prevalence of high-risk HPV types was 20.4% 

among U.S. women in the same age range. Within a decade 

following the U.S. introduction of quadrivalent HPV vaccine in 

2006, prevalence of HPV types 6, 11, 16, and 18 decreased 86% 

among females age 14 through 19 years and decreased 71% 

among females age 20 through 24 years. 

The National Cancer Institute’s (NCI) Surveillance, Epidemiology, 

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. 

HPV Secular Trends in 

the United States

● Genital HPV is the most 

common sexually transmitted 

infection in the U.S.

● Common among adolescents 

and young adults

● Before vaccine introduction

■ Estimated 79 million infected

■ 14 million new infections/year

● Within 10 years following 

vaccine introduction, 

prevalence of HPV types 6, 11, 

16, and 18 has decreased:

■ 86% among females age 

14 through 19 years

■ 71% among females age 

20 through 24 years
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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 

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 

spread of HPV. HPV transmission can be reduced, but not 

eliminated, with the consistent and correct use of physical 

barriers such as condoms. 

Cervical Cancer Screening

Most cases of and deaths from cervical cancer can be prevented 

through screening and treatment. The Pap test detects 

precancerous changes in cervical cells collected by a health 

care provider and placed on a slide (a conventional Pap) or in 

liquid media (liquid-based cytology). Clinical tests for HPV can 

be used as a primary screen either alone or in combination with 

cytology (co-test) or as triage after an equivocal cytology result.

Recommendations for cervical cancer screening in the United 

States are based on systematic evidence reviews by major 

medical and other organizations including the U.S. Preventive 

Services Task Force (USPSTF), American Cancer Society (ACS), 

and the American College of Obstetricians and Gynecologists 

(ACOG). Annual cervical cancer screening is not recommended 

for average-risk individuals. Instead, cytology testing is 

Cervical Cancer Screening

● Annual cervical cancer 

screening not recommended 

for average-risk individuals

● For ages 21 through 29 years, 

screen with cytology testing 

every 3 years 

● For ages 30 through 65 years, 

screen with choice of cytology 

test every 3 years, an HPV test 

alone every 5 years, or cytology 

test plus HPV test every 5 years

● USPSTF and ACOG have similar 

screening recommendations; 

ACS recommends that 

screening start at age 25 years 

for average-risk persons

● HPV vaccination does not 

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 vaccination does not eliminate the need for continued 

cervical cancer screening, since up to 30% of cervical cancers 

are caused by HPV types not prevented by the quadrivalent or 

bivalent vaccines, and 15% of cervical cancers are caused by 

HPV types not prevented by the 9-valent vaccine.

Human Papillomavirus Vaccines

A 9-valent recombinant protein subunit HPV vaccine (9vHPV, 

Gardasil 9) is licensed for use and is currently distributed in the 

United States. Two additional HPV vaccines remain licensed 

in the United States but are not currently distributed: a 

quadrivalent HPV vaccine (4vHPV, Gardasil), and a bivalent HPV 

vaccine (2vHPV, Cervarix). All of the vaccines prevent infection 

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 

addition, 4vHPV and 9vHPV vaccines prevent infections with 

HPV types 6 and 11, types that cause anogenital warts.

Characteristics

The antigen for HPV 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 (VLPs). The L1 proteins are produced 

by fermentation using Saccharomyces cerevisiae yeast; 9vHPV 

vaccine contains yeast protein. 9vHPV vaccine contains VLPs 

for nine HPV types: two types that cause anogenital warts 

(HPV types 6 and 11) and seven types that can cause cancers 

(HPV types 16, 18, 31, 33, 45, 52, and 58). 9vHPV vaccine is 

administered by intramuscular injection. Each dose of 9vHPV 

vaccine contains aluminum as an adjuvant. It contains no 

antibiotic or preservative. 

HPV Vaccines

● 9vHPV (Gardasil 9) is licensed 

and currently distributed in 

the U.S.

■ Prevents HPV types 6, 11, 

16, 18, 31, 33, 45, 52, 58

● 4vHPV and 2vHPV are licensed 

but not currently distributed in 

the U.S.

■ 4vHPV prevents HPV types 6, 

11, 16, 18

■ 2vHPV prevents HPV types 

16, 18

HPV Vaccine Characteristics

● 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)

● VLPs are noninfectious and 

nononcogenic

● Administer by intramuscular 

injection

● 9vHPV contains yeast protein

● 9vHPV contains aluminum 

adjuvant
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Vaccination Schedule and Use

HPV vaccination is recommended for females and males 

at age 11 or 12 years for prevention of HPV infections and 

HPV-associated diseases, including certain cancers. The 

vaccination series can be started at age 9 years. Catch-up 

HPV vaccination is recommended for all persons through age 

26 years who are not adequately vaccinated. Catch-up HPV 

vaccination is not recommended for all adults older than age 

26 years, since the public health benefit of vaccination in this 

age range is minimal. HPV vaccines are not licensed for use in 

persons older than age 45 years. 

HPV vaccines are administered as a 2- or 3-dose series, 

depending on age at initiation and medical conditions. 

A 2-dose series is recommended for persons who receive the 

first valid dose before their 15th birthday (except for persons 

with certain immunocompromising conditions). The second and 

final dose should be administered 6 through 12 months after 

the first dose (0, 6–12 month schedule). If dose 2 is administered 

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 

least 6 to 12 months after dose 1.

A 3-dose series is recommended for persons who receive the 

first valid dose on or after their 15th birthday, and for persons 

with primary or secondary immunocompromising conditions 

that might reduce cell-mediated or humoral immunity, such as 

B lymphocyte antibody deficiencies, T lymphocyte complete or 

partial defects, human immunodeficiency virus (HIV) infection, 

malignant neoplasm, transplantation, autoimmune disease, or 

immunosuppressive therapy, in whom immune response to 

vaccination may be attenuated. In a 3-dose schedule, dose 2 

should be administered 1–2 months after dose 1, and dose 3 

should be administered 6 months after dose 1 (0, 1–2, 6 month 

schedule). 

There is no maximum interval between doses. If the HPV 

vaccination schedule is interrupted, the vaccine series does 

not need to be restarted. For persons who already received 1 

dose of HPV vaccine before their 15th birthday, and now are 

age 15 years or older, the 2-dose series is considered adequate. 

If the series was interrupted after dose 1, dose 2 should be 

administered as soon as possible. 

Routine HPV vaccination is recommended beginning at 9 years 

of age for children with any history of sexual abuse or assault. 

Ideally, vaccine should be administered before any exposure 

to HPV through sexual contact. However, persons in the 

HPV Vaccination Schedule

● Routine vaccination 

recommended for females and 

males at age 11 or 12 years 

(minimum age 9 years)

● Catch-up vaccination 

recommended for all persons 

not adequately vaccinated 

through age 26 years

● Catch-up vaccination not 

recommended for all adults 

over age 26 years

● Shared clinical decision-making 

is recommended for some 

adults age 27 through 45 years

● Not licensed for adults over 

age 45 

HPV Vaccination Schedule

● 2-dose series

■ For immunocompetent 

persons who receive first valid 

dose before 15th birthday

■ 0, 6–12 month schedule

■ Minimum interval of 

5 months

● 3-dose series

■ For persons who receive 

first valid dose on or after 

15th birthday

■ For persons with 

primary or secondary 

immunocompromising 

conditions

■ 0, 1–2, 6 month schedule

● Series does not need to be 

restarted if the schedule 

is interrupted

● Prevaccination assessments 

not recommended

● No therapeutic effect on 

existing HPV infection, 

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.

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 

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 is highly immunogenic. More than 98% of 

recipients develop an antibody response to each covered HPV 

type within one month after completing the vaccine series. 

However, there is no known serologic correlate of protection 

and the minimum antibody titer needed for protection has not 

been determined. The high efficacy found in the clinical trials 

has precluded identification of this threshold. Further follow-up 

of vaccinated cohorts might allow determination of serologic 

correlates of protection in the future.

All licensed HPV vaccines have high efficacy for prevention 

of HPV vaccine-type-related persistent infection, CIN2+, and 

adenocarcinoma in-situ (AIS). Prelicensure, clinical efficacy for 

4vHPV was assessed in phase III clinical trials. To date, ongoing 

monitoring has demonstrated that vaccine effectiveness 

remains above 90%, with no waning of immunity through at 

least 10 to 12 years after immunization. 

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). 

HPV Vaccine Efficacy

● High vaccine efficacy

● More than 98% of recipients 

develop an antibody response 

to covered HPV types within 

one month after completing 

the series

● 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
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Human Papillomavirus

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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 

to Vaccination

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

Both 4vHPV and 9vHPV are produced using Saccharomyces 

cerevisiae (baker’s yeast) and thus are contraindicated for 

persons with a history of immediate hypersensitivity to yeast. 

2vHPV should not be used in persons with an anaphylactic 

allergy to latex as the pre-filled syringes might contain latex in 

the tip cap.

Vaccination during Pregnancy

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 

pregnancy. If a vaccine dose has been administered during 

pregnancy, no intervention is needed. Pregnancy testing is not 

needed before vaccination.

A pregnancy registry has been established by the manufacturer 

of 9vHPV. Women exposed to this vaccine around the time 

of conception or during pregnancy are encouraged to be 

registered by calling 1-800-986-8999 (merckpregnancyregistries.

com/gardasil9.html). 

Persons who are lactating or breastfeeding can receive 

HPV vaccine.

Vaccine Safety

HPV vaccine is generally well-tolerated. Safety has been 

well-established from prelicensure trials and postlicensure 

monitoring and evaluation. 

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 

HPV Vaccine Contraindications 

and Precautions

● Contraindication

■ Severe allergic reaction to 

a vaccine component or 

following a prior dose 

■ History of immediate 

hypersensitivity to yeast 

(4vHPV and 9vHPV only)

■ Anaphylactic allergy to latex 

(2vHPV only)

● Precaution

■ Moderate or severe acute 

illnesses (defer until 

symptoms improve)

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 

dose(s) 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 manufacturer

● Pregnancy testing is not 

needed before vaccination
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vaccination was reported by 10% to 13% of HPV vaccine 

recipients. 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. Although rare, 

anaphylaxis can occur. No other serious adverse events have 

been significantly associated with any HPV vaccine, based on 

monitoring by CDC and FDA. 

A variety of systemic adverse events following vaccination were 

reported by vaccine recipients, including nausea, dizziness, 

myalgia, and malaise. However, these symptoms occurred with 

similar frequency among vaccine and placebo recipients.

Postlicensure monitoring of reports from the Vaccine 

Adverse Event Reporting System (VAERS) did not identify any 

unexpected adverse event, was consistent with data from 

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 

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 vaccinepreventable 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.

HPV Vaccine Safety

● HPV vaccine is generally welltolerated

● Local reactions (pain, redness, 

swelling)

■ 20%-90%

● Fever (100%)

■ 10%-13% (similar to reports in 

placebo recipients)

● Anaphylaxis is rare, but can 

occur 

● No other serious adverse 

reactions associated with any 

HPV vaccine
176

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NOTES