Genital Human Papillomavirus (HPV)

HPV Curriculum
Genital Human Papillomavirus

(HPV)
1
HPV Curriculum
Learning Objectives
Upon completion of this content, the learner will be able to
1. Describe the epidemiology of genital HPV infection in the
U.S.;
2. Describe the pathogenesis of genital HPV;
3. Discuss the clinical manifestations of genital HPV
infection;
4. Identify methods used to diagnose genital warts and
cervical cellular abnormalities;
5. Discuss CDC-recommended treatment regimens for
genital warts;
6. Summarize appropriate prevention counseling messages
for genital HPV infection;
7. Describe public health measures for the prevention of
genital HPV infection.
2
HPV Curriculum
Lessons
I. Epidemiology of genital HPV infection in the
U.S.
II. Pathogenesis
III. Clinical manifestations and sequelae
IV. Diagnosis of genital warts and cervical
cellular abnormalities
V. Patient management
VI. Patient counseling and education
VII. Partner management and public health
measures
3
HPV Curriculum
Lesson I: Epidemiology of
Genital HPV Infection in the
U.S.
4
HPV Curriculum Epidemiology
Introduction
• Genital HPV is one of the most common
STDs
• More than 40 HPV types can infect the

genital tract
5
Introduction
• HPV types are divided into two groups based
on their association with cancer.
– Low-risk types (nononcogenic) associated with
genital warts and mild Pap test abnormalities
– High-risk types (oncogenic) associated with
moderate to severe Pap test abnormalities,
cervical dysplasia and cervical cancer, and other
cancers
• Most genital HPV infections are transient,
asymptomatic, and have no clinical
consequences.
6
Incidence in the U.S.
• Estimated annual incidence of sexually-

transmitted HPV infection is 14.1 million
• Estimated $1.7 billion spent annually in

direct medical costs to treat conditions
associated with genital HPV infection
7
Prevalence in the U.S.

• 100% of sexually active men and
women acquire genital HPV at some
point in their lives.
• An estimated 79 million females aged
14–59 years are infected with HPV
infection.
8
Incidence and Prevalence of

HPV-associated Diseases
• Genital warts
– Incidence may be as high as 100/100,000.
– An estimated 1.4 million may be affected at
any one time.
• Cervical cancer
– Rates of cervical cancer have fallen by
approximately 75% since the introduction of
Pap screening programs.
– Incidence is estimated at 8.1/100,000.
9
Age-Adjusted Delay-Adjusted Incidence of
Cervical Cancer by Race: 1975–2009
10
Transmission of Genital HPV

• Predominantly associated with sexual
activity
• Can occur from asymptomatic and
subclinical patients
• Infectivity after treatment of genital warts or
cervical cellular abnormalities is unknown
• Condoms may reduce risk
11
Risk Factors for Women

• Young age
• Sexual behavior
– Risk increases with increasing number of recent
and lifetime sex partners
• Sexual behavior of sex partners–risk
increases for women whose sex partners had
multiple sex partners
• Immune status–HPV more likely to be
detected in immune-suppressed women
12
Risk Factors for Men
• Risk increases with increasing number

of recent and lifetime sex partners
• Being uncircumcised increases risk
13
HPV Curriculum
Lesson II: Pathogenesis
14
HPV Curriculum Pathogenesis
Virology
• Double-stranded DNA virus that belongs to
the Papillomaviridae family
• Genital types have specific affinity for genital
skin and mucosa
• Infection identified by the detection of HPV
DNA
15
HPV Genotyping System

Genital HPV types are generally characterized
in terms of oncogenic potential.
• Low-risk types (nononcogenic types)
– Most genital warts caused by HPV types 6 and 11
– Recurrent respiratory papillomatosis associated with HPV
types 6 and 11
• High-risk types (oncogenic types)

– HPV types 16 and 18 found in 70% of cervical cancers
– Most women with high-risk HPV infection have normal Pap
test results and never develop cellular changes or cervical
16
cancer.
Pathology
• HPV infects the basal cell layer of
stratified squamous epithelium and
stimulates cellular proliferation.
• Affected cells display a broad spectrum of

changes, ranging from benign
hyperplasia, to dysplasia, to invasive
carcinoma.
17
Natural History of HPV

• Most genital HPV infections are transient,
asymptomatic (subclinical), and have no clinical
consequences in immunocompetent individuals.
• Time to development of clinical manifestations

is variable.
• Median duration of new cervical infections is 8

months, but varies.
– 90% of infections clear within 2 years
– Gradual development of an effective immune
response is the likely mechanism for HPV DNA
clearance. 18
Natural History of HPV-continued
• Persistent HPV infection

– Not cleared by the immune system
– Characterized by persistently detectable type-
specific HPV DNA
– Persistent oncogenic HPV infection is most
important risk factor for precancerous cervical
cellular changes and cervical cancer.
19
HPV Curriculum
Lesson III: Clinical

Manifestations and Sequelae
20
HPV Curriculum
HPV-associated cancers United States, 2004-2008

Estimated+
Average annual HPV HPV 16/18
Anatomic Area number of cases* attributable attributable
Cervix 11,967 11,500 9,100
Vagina 729 500 400
Vulva 3,136 1,600 1,400
Anus (F) 3,089 2,900 2,700
Oropharynx (F) 2,370 1,500 1,400
Total (Females) 21,291 18,000 15,000
Penis 1,046 400 300

Anus (M) 1,678 1,600 1,500
Oropharynx (M) 9,356 5,900 5,600
Total (Males) 12,080 7,900 7,400
* Defined by histology and anatomic site; Watson M et al. Cancer 2008. Data source: National Program of
Cancer Registries and SEER, covering 100% coverage of US population. + Gillison ML, et al. Cancer 2008 .
Ref: Human Papillomavirus-Associated Cancers MMWR 2012;61(15):258-261.
HPV Curriculum Clinical Manifestations
Clinical Manifestations and Sequelae

• In most cases, genital HPV infection is transient
and has no clinical manifestations or sequelae.
• Clinical manifestations of genital HPV infection
include
– Genital warts,*
– Cervical cellular abnormalities detected by Pap tests,*
– Some anogenital squamous cell cancers,
– Some oropharyngeal cancers, and
– Recurrent respiratory papillomatosis.
*Two most common clinically significant manifestations of genital HPV infection

22
Genital Warts-Appearance
• Condylomata acuminata
– Cauliflower-like appearance
– Skin-colored, pink, or hyperpigmented
– May be keratotic on skin; generally nonkeratinized on mucosal
surfaces
• Smooth papules
– Usually dome-shaped and skin-colored
• Flat papules
– Macular to slightly raised
– Flesh-colored, with smooth surface
– More commonly found on internal structures (i.e., cervix), but
also occur on external genitalia
• Keratotic warts
– Thick horny layer that can resemble common warts or
seborrheic keratosis 23
Genital Warts-Location
• Most commonly occur in areas of coital friction
• Perianal warts do not necessarily imply anal
intercourse.
– May be secondary to autoinoculation, sexual activity other
than intercourse, or spread from nearby genital wart site
• Intra-anal warts are seen predominantly in patients
who have had receptive anal intercourse.
• HPV types causing genital warts can occasionally
cause lesions on oral, upper respiratory, upper GI,
and ocular locations.
• Patients with visible warts are frequently
simultaneously infected with multiple HPV types.
24
Genital Warts-Symptoms
• Genital warts usually cause no symptoms. Symptoms that
can occur include:
– Vulvar warts-dyspareunia, pruritis, burning discomfort;
– Penile warts-occasional itching;
– Urethral meatal warts-hematuria or impairment of urinary stream;
– Vaginal warts-discharge/bleeding, obstruction of birth canal
(secondary to increased wart growth during pregnancy); and
– Perianal and intra-anal warts-pain, bleeding on defecation, itching
• Most patients have fewer than ten genital warts, with total
wart area of 0.5–1.0 cm2.
25
Genital Warts-Duration and

Transmission
• May regress spontaneously, or persist
with or without proliferation.
– Frequency of spontaneous regression is
unclear, but estimated at 10–30% within
three months.
– Persistence of infection occurs, but
frequency and duration are unknown.
– Recurrences after treatment are common.
26
Genital Warts and High-Risk HPV

• High-risk HPV types occasionally can be
found in visible warts and have been
associated with squamous intrepithelial
lesions (squamous cell carcinoma in situ,
Bowenoid papulosis, Erythroplasia of Queyrat,
or Bowen’ s disease of the genitalia).
• The lesions can resemble genital warts.
• Unusual appearing genital warts should be
biopsied.
27
Genital Warts in
Preadolescent Children
• May be due to sexual abuse although this
condition is not diagnostic for sexual abuse.
Their appearance should prompt an
evaluation by a clinician.
• May also result from vertical transmission,
transmission of nongenital HPV types to
genital surface, and possibly fomite
transmission, although fomite transmission
has never been documented.
28
Perianal Warts
Source: Seattle STD/HIV Prevention Training Center at the University of 29

Washington/ UW HSCER Slide Bank
Vulvar Warts
30
Source: Reprinted with permission of Gordon D. Davis, MD.
Penile Warts
31
Source: Cincinnati STD/HIV Prevention Training Center
Intrameatal Wart
32
Source: Cincinnati STD/HIV Prevention Training Center
Cervical Cellular Abnormalities
• Usually subclinical
• Lesions associated with these abnormalities can
be detected by Pap test or colposcopy, with or
without biopsy.
• Can be caused by HPV
• Low-grade lesions often regress spontaneously
without treatment.
33
Classification of Cervical Cellular

Abnormalities
2001 Bethesda System
• Atypical Squamous Cells (ASC-US and ASC-H)
are cells that do not appear to be completely
normal
– Atypical Squamous Cells of Undetermined
Significance (ASC–US)
• Changes are often caused by HPV infection.
• Changes are usually mild.
– Atypical Squamous Cells cannot exclude a High-

Grade Squamous Intraepithelial Lesion (ASC–H).
• Changes are more likely to be associated with precancerous
abnormalities than ASC-US. 34
Classification of Cervical Cellular

Abnormalities-continued
• Low-grade squamous intraepithelial lesion (LSIL)
– Usually transient, caused by HPV infection
• High-grade squamous intraepithelial lesion (HSIL)

– Generally changes due to persistent infection with a
high-risk HPV type
– Lesions associated with HSIL have a higher risk for
progression to cervical cancer.
35
Anogenital Squamous Cell Cancers
• HPV infection is causally associated with cervical

cancer and other anogenital squamous cell
cancers (e.g., anal, penile, vulvar, vaginal).
• Over 99% of cervical cancers have HPV DNA
detected within the tumor.
• Persistent infection with a high-risk HPV type is

necessary, but not sufficient, for the development
of cervical cancer.
36
Recurrent Respiratory
Papillomatosis
• HPV infections in infants and children
may present as warts in the throat, also
known as juvenile onset recurrent
respiratory papillomatosis (JORRP).
• Respiratory papillomatosis is a rare

condition, usually associated with HPV
types 6 and 11.
37
HPV Curriculum
Lesson IV: Diagnosis of

Genital Warts and Cervical
Cellular Abnormalities
38
HPV Curriculum Diagnosis
Diagnosis of Genital Warts

• Diagnosis is usually made by visual
inspection with bright light.
• Consider biopsy when
– Diagnosis is uncertain;
– Patient is immunocompromised;
– Warts are pigmented, indurated, or fixed;
– Lesions do not respond or worsen with standard
treatment; or
– There is persistent ulceration or bleeding.
39
Diagnosis of Genital Warts-continued

• Use of type-specific HPV DNA tests for routine
diagnosis and management of genital warts is not
recommended.
• Application of acetic acid to evaluate external genitalia
is not routinely recommended due to its low specificity.
• Acetowhitening will occur at sites of prior trauma or
inflammation.
• External genital warts are not an indication for cervical
colposcopy or increased frequency of Pap test
screening (assuming patient is receiving screening at
intervals recommended by her healthcare provider).
40
Differential Diagnosis of
Genital Warts
• Other infections
– Condylomata lata
• Tend to be smoother, moist, more rounded, and
darkfield-positive for Treponema pallidum
– Molluscum contagiosum
• Papules with central dimple, caused by a pox virus;
rarely involves mucosal surfaces
• Acquired dermatologic conditions

– Seborrheic keratosis
– Lichen planus
– Fibroepithelial polyp, adenoma
– Melanocytic nevus
– Neoplastic lesions 41
Differential Diagnosis of
Genital Warts-continued
• Normal anatomic variants
– “Pink pearly penile papules”
– Vestibular papillae (micropapillomatosis labialis)
– Skin tags (acrochordons)
• External genital squamous intraepithelial

lesions (SIL)
– Squamous cell carcinoma in situ
– Bowenoid papulosis
– Erythroplasia of Queyrat
– Bowen’s disease of the genitalia
42
Diagnosis of Cervical Cellular

Abnormalities
• Cytology (Pap test)
– Useful screening test to detect cervical
cell changes
– Provides indirect evidence of HPV

because it detects squamous epithelial
cell changes that are almost always due
to HPV
43

• HPV DNA tests
– FDA-approved:
• To triage women with ASC-US Pap test results, and
• As an adjunct to Pap test screening for cervical cancer in
women 30 years or older.
• HPV DNA tests should not be used

– In men,
– In adolescents <21 years,
– To screen partners of women with Pap test
abnormalities,
– To determine who will receive HPV vaccine, or
– STD screening for HPV.
44

• Colposcopy
– Indication guided by physical exam or Pap test findings with
or without HPV DNA test findings
• Cervical biopsy
– May be indicated if there is/are
• Visible exophytic lesions on cervix
• Pap test with HSIL, ASC-H, or other findings
• For more information on guidelines for managing

women with cervical cytologic abnormalities, refer to
2006 Consensus Guidelines for Management of
Women with Cervical Cytologic Abnormalities
http://www.asccp.org/consensus/cytological.shtml
45
HPV Curriculum
Lesson V: Patient
Management
46
HPV Curriculum Management
General Treatment of
Genital Warts
• Primary goal is removal of warts.
• If left untreated, genital warts may regress
spontaneously or persist with or without
proliferation.
• In most patients, treatment can induce wart-free
periods.
• Currently available therapies may reduce, but
probably do not eliminate infectivity.
• Effect of current treatment on future transmission
is unclear.
47
General Treatment of
Genital Warts-continued
• No evidence that presence of genital warts or
their treatment is associated with development
of cervical cancer.
• Some patients may choose to forgo treatment
and await spontaneous resolution.
• Consider screening persons with newly
diagnosed genital warts for other STDs (e.g.,
chlamydia, gonorrhea, HIV, syphilis).
48
Treatment Regimens
• Patient-applied and provider-administered
therapies are available.
• Providers should be knowledgeable about and
have available, at least one patient-applied and
one provider-administered treatment.
• Choice of treatment should be guided by
– Patient preference,
– Available resources,
– Experience of the healthcare provider,
– Location of lesion(s), and
– Pregnancy status.
49
Treatment Regimens-continued
• Factors influencing treatment selection include
– Wart size,
– Number of warts,
– Anatomic site of wart,
– Wart morphology,
– Patient preference,
– Cost of treatment,
– Convenience, and
– Adverse effects.
50
Treatment Response
• Affected by
– Number, size, duration, and location of warts, and immune
status
– In general, warts located on moist surfaces and in
intertriginous areas respond better to topical treatment than do
warts on drier surfaces.
• Many patients require a course of therapy over several
weeks or months rather than a single treatment.
– Evaluate the risk-benefit ratio of treatment throughout the
course of therapy to avoid over-treatment.
• There is no evidence that any specific treatment is
superior to any of the others.
– The use of locally developed and monitored treatment
algorithms has been associated with improved clinical
outcomes
51
Recurrence After Treatment

• As many as two-thirds of patients will
experience recurrences of warts within 6–12
weeks of therapy; after 6 months most
patients have clearance.
– If persistent after 3 months, or if there is poor
response to treatment, consider biopsy to exclude
a premalignant or neoplastic condition, especially
in an immunocompromised person.
• Treatment modality should be changed if
patient has not improved substantially after 3
provider-administered treatments or if warts
do not completely clear after 6 treatments
52
Complications
• Complications rarely occur, if treatments for
warts are employed properly.
– Depressed or hypertrophic scars are uncommon,
but can occur, especially if the patient has had
insufficient time to heal between treatments.
– Rarely, treatment can result in disabling chronic
pain syndromes (e.g., vulvodynia or
hyperesthesia of treatment site).
• Patients should be notified that persistent

hypopigmentation or hyperpigmentation are
common with some treatments.
53
CDC-Recommended Regimens For External

Genital Warts (Patient-Applied)
• Podofilox 0.5% solution or gel*
– Apply solution with cotton swab or gel with a finger to visible warts twice a day for
3 days, followed by 4 days of no therapy.
– Cycle may be repeated as needed up to 4 cycles
or
• Imiquimod 5% cream*
– Apply cream once daily at bedtime, 3 times a week for up to 16 weeks.
– Treatment area should be washed with soap and water 6–10 hours after
application
or
• Sinecatechins 15% ointment*,**
– Apply ointment 3 times daily for up to 16 weeks.
– Do not wash off post-application
*Safety not established in pregnancy

**Safety not established in HIV- or HSV-co-infected individuals
54

Genital Warts (Patient-Applied)-continued
• Using patient-applied treatments
– Provider should identify warts for treatment and teach patients how to apply
substance.
– Patient must be able to identify and reach warts to be treated.
– Podofilox 0.5% solution or gel, an antimitotic drug that destroys warts, is
relatively inexpensive, easy to use, and safe.
– Most patients experience mild or moderate pain or local irritation after
treatment with podofilox.
– Imiquimod is a topically active immune enhancer that stimulates production of
interferon and other cytokines.
– Local inflammatory reactions are common with use of imiquimod and
sinecatechins; these reactions include redness and irritation and are usually
mild to moderate.
• Follow-up is not required, but may be useful several weeks
into therapy to determine appropriateness of medication use
55
and response to treatment.
Genital Warts (Provider-Administered)
• Cryotherapy with liquid nitrogen or cryoprobe
– Repeat applications every 1–2 weeks, or
• Podophyllin resin 10%–25%* in compound tincture of benzoin
– Apply a small amount to each wart and allow to air dry
– To avoid toxicity
• Application should be limited to < 0.5 mL of podophyllin or < 10 cm 2 of warts per
session
• No open lesions or wounds should exist in the area to which treatment is
administered
– Treatment may be repeated weekly if needed, or
• Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80%–90%
– Apply small amount only to warts and allow to dry
– Treatment may be repeated weekly if needed, or
• Surgical removal - tangential scissor excision, tangential shave excision,
curettage, or electrosurgery
56
*Safety not established in pregnancy
Alternative Treatment Regimens
• Alternative Treatment Regimens include

treatment options that might be
associated with more side effects and/or
less data on efficacy including
– Intralesional interferon,
– Carbon dioxide laser and surgery, and
– Topical cidofovir.
57
CDC-Recommended Regimens for

Exophytic Cervical Warts
• Biopsy needed, high-grade squamous

intraepithelial lesions (SIL) must be
excluded before treatment is initiated.
• Management should include biopsy and
consultation with a specialist.
58
CDC-Recommended
Regimens for Vaginal Warts
Treat only if symptomatic, since most treatments also
affect normal tissue and can cause scarring and pain.
• Cryotherapy with liquid nitrogen

– Use of a cryoprobe in the vagina is not recommended
because of risk for vaginal perforation and fistula formation.
or
• TCA or BCA 80%–90% applied to warts
– Apply small amount only to warts and allow to dry (white
“frosting” develops).
– Treatment may be repeated weekly if needed.
59
CDC-Recommended Regimens
for Urethral Meatal Warts

or
• Podophyllin 10%–25% in compound tincture
of benzoin
– Treatment area must be dry before contact with
normal mucosa.
– Treatment may be repeated weekly, if needed.
60
CDC-Recommended
Regimens for Anal Warts
or
• TCA or BCA 80%–90% applied to warts
– Apply small amount only to warts and allow to dry
(white “frosting” develops).
– Treatment may be repeated weekly if needed.
or
• Surgical removal
61
Management in Pregnancy
• Genital warts can proliferate and become more friable
during pregnancy.
• Cytotoxic agents (podophyllin, podofilox, imiquimod)
should not be used.
• Cryotherapy, TCA, BCA, and surgical removal may be
used.
• HPV types 6 and 11 can cause recurrent respiratory
papillomatosis in children. The route of transmission is not
completely understood.
• Prevention value of cesarean delivery is unknown; thus,
C-section should not be performed solely to prevent
transmission to neonate.
62
Genital Warts in HIV-Infected Patients

• No data that treatment should be different
• Larger, more numerous warts
• Might not respond as well to therapy
• More frequent recurrence of lesions after treatment
• Squamous cell carcinomas arising in or resembling
genital warts might occur more frequently among
immunosuppressed persons, therefore, requiring
biopsy for confirmation of diagnosis for suspicious
cases, and referral to a specialist.
63
Pap Test Screening in

Immunodeficient Patients
• Provide cervical Pap test screening every 6
months for 1 year, then annually for all HIV-
infected women with or without genital warts.
• Anal Pap tests and anoscopy
– There is an increased incidence of anal cancer in
HIV-infected MSM. Some experts screen for anal
intraepithelial neoplasia by cytology-however, this is
not routinely recommended, because evidence is
limited on natural history of anal intraepithelial
neoplasias, reliability of screening methods, safety
and response to treatments, and programmatic
considerations.
64
Squamous Cell Carcinoma in situ

• Patients in whom squamous cell carcinoma
in situ of the genitalia is diagnosed should
be referred to a specialist for treatment.
• Ablative modalities usually are effective, but

careful follow-up is essential.
65
Genital Wart Follow-Up

• Counsel patients to
– Watch for recurrences,
– Continue regular Pap screening at same intervals as recommended
for women without genital warts, and
– Communicate to current sex partners about genital warts and the
risk of transmission. Patients should have no sexual activity until
warts are gone.
• After visible warts have cleared, follow-up
evaluation is not mandatory, but provides an
opportunity to
– Monitor or treat complications of therapy,
– Document absence of warts, and
– Reinforce patient education and counseling messages.
• Offer patients concerned about recurrences a66

follow-up evaluation 3 months after treatment.
Treatment of Cervical Dysplasia

• For more information on managing women with
cervical dysplasia, refer to the following
sources:
– 2006 Consensus Guidelines for the Management
of Women with Cervical Cytologic Abnormalities
http://www.asccp.org/consensus/cytological.shtml
– CDC National Breast and Cervical Cancer Early
Detection Program
http://www.cdc.gov/cancer/nbccedp/index.htm
67
HPV Curriculum
Lesson VI: Patient Counseling
and Education
68
HPV Curriculum Patient Counseling and Education
The Nature of HPV Infection

• Genital HPV infection is common in sexually active
adults.
– The majority of sexually active adults will have HPV infection at
some point, although most will never know because infection
will be asymptomatic and will clear on its own.
• Natural history of HPV infection is usually benign

– Low-risk genital HPV types are associated with mild Pap test
abnormalities and genital warts.
– High-risk types are associated with mild to severe Pap test
abnormalities and, rarely, cancers of the cervix, vulva, vagina,
anus, penis, oropharynx.
– Most women infected with HPV do not develop cervical cancer.
• Genital warts have a high recurrence rate after treatment.

69
Transmission Issues
• Usually sexually transmitted
• Infection is often shared between partners
• Determining source of infection is usually difficult
(incubation period variable)
• Recurrences usually are not reinfection
• Transmission risk to current and future partners
after treatment is unclear.
• Likelihood of transmission and duration of
infectivity with or without treatment are unknown.
• Value of disclosing a past diagnosis of genital
HPV infection to future partners is unclear,
although candid discussions about past STD
should be encouraged. 70
Risk Reduction
• Assess patient’s behavior-change potential.
• Develop individualized risk-reduction plans with the patient
for lasting results.
• Discuss prevention strategies such as abstinence, mutual
monogamy, condoms, limiting number of sex partners, etc.
• Consistent and correct male condom use reduces risk for
genital HPV acquisition and HPV-associated diseases
(e.g., genital warts and cervical cancer).
– HPV infections can occur in areas that are not covered
or protected by a condom (e.g., scrotum, vulva, or
perinanus).
71
Patient Counseling and

Education Resources
• Division of STD Prevention http://
www.cdc.gov/std/hpv/default.htm
• American Sexual Health Association, National HPV and
Cervical Cancer Prevention Resource Center http://
www.ashastd.org/std-sti/hpv.html
• CDC Cervical Cancer Screening Fact Sheet
http://www.cdc.gov/cancer/cervical/pdf/cc_basic.pdf
• National Cancer Institute Cervical Cancer Screening
Information For Patients
http://www.cancer.gov/cancertopics/pdq/screening/cervical
/Patient
• American Society of Colposcopy and Cervical Cancer
Pathology http
://www.asccp.org/EducationeLearning/EducatetheEducat
orsbrHPVResourceCenter/tabid/5980/Default.aspx
72
HPV Curriculum
Lesson VII: Partner Management

and Public Health Measures
73
HPV Curriculum Prevention
Partner Management for Patients

with Genital Warts
• Sex partner examination is not necessary for
management of genital warts. There are no data to
indicate that reinfection plays a role in recurrences.
• Providing treatment solely for the purpose of
preventing future transmission cannot be
recommended because value of treatment in
reducing infectivity is not known.
• Counseling of sex partners provides an opportunity
for these partners to
– Learn about the implications of having a partner who has
genital warts and about the potential for disease
transmission, and
– Receive STD and Pap screening, if necessary. 74
Cervical Cancer Screening

• The key strategy to prevent cervical cancer is regular
cervical cancer screening (Pap test screening) for all
sexually active women ≥21 years.
• New technologies, including liquid-based cytology and
testing for high-risk HPV types, may offer some benefits.
• Liquid-based cytology is an alternative to conventional Pap
tests
• Several organizations provide guidelines for cervical cancer
screening, including
– American Cancer Society (ACS),
– American College of Obstetricians and Gynecologists (ACOG),
– U.S. Preventive Services Task Force (USPSTF), and
– American Society for Colposcopy and Cervical Pathology
75
(ASCCP).
Special Considerations
• Pregnant women should have a Pap test as

part of routine prenatal care
• Anal Pap test screening in HIV-positive

persons not routinely recommended
76
Reporting Requirements
• Genital HPV infection is not a reportable

infection.
• Genital warts are reportable in some states.
• Some states have made cervical precancer
reportable.
• Check with state or local health department
for reporting requirements for HPV
associated outcomes in your area.
77
HPV Vaccines
• Two types
– Bivalent vaccine (HPV2) protects against HPV 16 and 18-associated
cervical precancers.
– Quadrivalent vaccine (HPV4) protects against HPV 6, 11, 16, and 18-
associated genital warts, cervical precancers, vulvar and vaginal
precancers, and anal precancers.
• Administration
– Either vaccine is recommended for routine vaccination of females aged
11 or 12 years. HPV4 is recommended for routine vaccination of
males aged 11 or 12 years. This vaccine can be given at 9 or 10 years
of age.
– Vaccination is also recommended for 13–26 year old females and
13–21 year old males who have not had any or all the doses at a
younger age.
– MSM should be vaccinated through age 26 years.
– Immunocompromised persons (including those with HIV-infection)
should be vaccinated through age 26 years.
78
HPV Vaccines (continued)

• Dosing
– Three-dose series intramuscularly over a six-month period
• Women who have received HPV vaccine should continue

routine cervical cancer screening.
– Thirty percent of cervical cancers are caused by HPV types other than
16 and 18
• CDC has a website with additional vaccine information
http://www.cdc.gov/vaccines/pubs/ACIP-list.htm#hpv
79
HPV Curriculum
Case Study
80
HPV Curriculum Case Study
History
• Anne Drew: 34-year-old woman who wants to get "checked
out" because Jonathan, her sex partner, has small solid
"bumps" on the skin on the shaft of his penis.
• Jonathan told her that he was diagnosed and treated for
genital warts about a year ago, and his healthcare provider
told him they could recur.
• No history of abnormal Pap smears and no history of STDs
• Last Pap smear performed 4 months ago
• Sexually active with men only since age 16; has had a total of
7 sex partners over her lifetime
• Currently sexually active with 1 partner for the last 8 months
• Uses oral contraceptives for birth control
81
Question
1. What should be included in Ms. Drew’s
evaluation?
82
Physical Examination
• Vital signs: blood pressure 96/74, pulse 78,
respiration 13, temperature 37.1° C
• Cooperative, good historian
• Chest, heart, musculoskeletal, and abdominal
exams within normal limits
• Pelvic exam is normal
• Visual inspection of the genitalia reveals multiple
small (<0.5 cm), flesh-colored, papular lesions in the
perineal area
83
Questions
2. What is the differential diagnosis for the
papular genital lesions?
3. What is the most likely diagnosis
based on history and physical
examination?
4. Which laboratory tests should be
ordered or performed?
84
Patient Management
The following genital warts management options are
discussed with Ms. Drew:
• Patient-applied therapy
– Podofilox 0.5% solution or gel
– Imiquimod 5% cream
– Sinecatechins 15% ointment
• Provider-administered therapy
– Cryotherapy with liquid nitrogen or cryoprobe
– Podophyllin resin 10%–25% in compound tincture of
benzoin
– Trichloroacetic acid (TCA) or bichloroacetic acid (BCA)
80%–90%
• Surgical removal
85
• No intervention
Questions
5. What is the effect of treatment on future
transmission? What is the possibility of
recurrence after treatment?
6. What are appropriate counseling messages
for Ms. Drew about genital warts and HPV
infection?
7. What condition could cause a substantial
increase in the number and size of Ms.
Drew’s genital warts?
86

Genital Human Papillomavirus (HPV)

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HPV Curriculum

Genital Human Papillomavirus

• More than 40 HPV types can infect the

Incidence in the U.S.

• Estimated annual incidence of sexually-

• Estimated $1.7 billion spent annually in

Prevalence in the U.S.

Incidence and Prevalence of

Transmission of Genital HPV

Risk Factors for Women

Risk Factors for Men

• Risk increases with increasing number

• Being uncircumcised increases risk

Lesson II: Pathogenesis

HPV Genotyping System

• High-risk types (oncogenic types)

• Affected cells display a broad spectrum of

Natural History of HPV

• Time to development of clinical manifestations

• Median duration of new cervical infections is 8

Natural History of HPV-continued

• Persistent HPV infection

Lesson III: Clinical

HPV-associated cancers United States, 2004-2008

Penis 1,046 400 300

Clinical Manifestations and Sequelae

*Two most common clinically significant manifestations of genital HPV infection

Genital Warts-Duration and

Genital Warts and High-Risk HPV

Source: Seattle STD/HIV Prevention Training Center at the University of 29

Cervical Cellular Abnormalities

Classification of Cervical Cellular

– Atypical Squamous Cells cannot exclude a High-

Classification of Cervical Cellular

• High-grade squamous intraepithelial lesion (HSIL)

Anogenital Squamous Cell Cancers

• HPV infection is causally associated with cervical

• Persistent infection with a high-risk HPV type is

• Respiratory papillomatosis is a rare

Lesson IV: Diagnosis of

Diagnosis of Genital Warts

Diagnosis of Genital Warts-continued

• Acquired dermatologic conditions

• External genital squamous intraepithelial

Diagnosis of Cervical Cellular

– Provides indirect evidence of HPV

Diagnosis of Cervical Cellular

• HPV DNA tests should not be used

Diagnosis of Cervical Cellular

• For more information on guidelines for managing

Recurrence After Treatment

• Patients should be notified that persistent

CDC-Recommended Regimens For External

*Safety not established in pregnancy

CDC-Recommended Regimens For External

Alternative Treatment Regimens

• Alternative Treatment Regimens include

CDC-Recommended Regimens for