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**Genital Human Papillomavirus (HPV) Infection**

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**Learning Objectives**

1.  Upon completion of this content, the learner will be able to:

2.  Describe the epidemiology of genital HPV infection in the U.S.

3.  Describe the pathology of genital HPV.

4.  Discuss the clinical manifestations of genital HPV infection.

5.  Identify methods used to diagnose genital warts and cervical
    cellular abnormalities.

6.  Discuss the CDC-recommended treatment regimens for genital warts.

7.  Summarize appropriate prevention counseling messages for genital HPV
    infection.

8.  Describe public health measures for the prevention of genital HPV
    infection.

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**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

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I.  **Epidemiology of Genital HPV Infection in the U.S.**

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A.  Introduction

    1.  Genital HPV infection is one of the most common STDs.

    2.  More than 30 types of HPV are sexually transmitted and can
        infect the genital tract.

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3.  Genital HPV types are divided into two groups, based on their
    association with cervical cancer.

    a.  Infections with low-risk types can cause genital warts and
        benign or low-grade cervical cell changes (mild Pap test
        abnormalities) but are not associated with cervical cancer.

    b.  Infections with high-risk types can cause low-grade cervical
        cell changes, high-grade cervical cell changes that are
        precursors to cancer (moderate to severe Pap test
        abnormalities), and, in rare cases, cancers of the cervix,
        vulva, anus, and penis.

4.  Most genital HPV infections, whether caused by low-risk or high-risk
    types, are transient (go away on their own), asymptomatic, and have
    no clinical consequences.

5.  Incidence and prevalence information on genital HPV infection is
    incomplete because:

    a.  It is not a reportable infection in any state (genital warts are
        reportable in a few states).

    b.  Most infections are not diagnosed because they are brief,
        asymptomatic, or subclinical (have no visible clinical
        manifestations) and have no clinical consequences.

    c.  Most studies estimating incidence and prevalence have been
        performed in women, with little data about men.

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B.  Incidence in the U.S.

    1.  The estimated annual incidence of sexually transmitted HPV
        infection is 6.2 million cases.

    2.  An estimated \$1.6 billion spent annually in direct medical
        costs to treat consequences of genital HPV infection.

    3.  An estimated 20 million people (15% of the population) currently
        have a detectable genital HPV infection.

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C.  Prevalence in the U.S.

    1.  It is estimated that at least 50% of sexually active men and
        women acquire genital HPV infection at some point in their
        lives.

    2.  A recent estimate suggests that 80% of women will have acquired
        genital HPV infection by age 50.

    3.  An estimated 9.2 million sexually active youth 15-24 years of
        age are currently infected with genital HPV.

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D.  Incidence and prevalence of genital HPV-associated diseases

    1.  Genital warts

        a.  Prevalence estimates for genital warts are relatively
            imprecise.

        b.  Limited data suggest that annual incidence may be as high as
            100 per 100,000 population.

        c.  An estimated 1.4 million (1% of the sexually active U.S.
            population) is affected at any one time.

    2.  Cervical cancer

        a.  Rates of cervical cancer have fallen by approximately 75%
            since the introduction of Pap screening programs.

        b.  Cervical cancer incidence in the U.S. is currently estimated
            to be 8.3 per 100,000 women.

            1.  Approximately 10,520 new cases annually

            2.  Approximately 3,900 deaths annually

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c.  Graph: Delay Adjusted Incidence and U.S. Death Rates of Cervical
    Cancer by Year of Diagnosis and Race: 1973-2001. Although cervical
    cancer rates continue to decline for both white and black women in
    the U.S., the burden of disease continues to be on black women.

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E.  Transmission of genital HPV infection

    1.  Predominantly associated with sexual activity

    2.  Likely requires contact with viable HPV and microtrauma to skin
        or mucous membranes

    3.  Can occur from asymptomatic and subclinical patients

    4.  Infectivity after treatment of genital warts or cervical cell
        abnormalities is unknown.

    5.  Transmission by fomites (inanimate objects such as environmental
        surfaces and clothing) has never been documented.

    6.  Rarely, genital HPV infection with low-risk types is transmitted
        from mother to baby during delivery and causes respiratory tract
        warts in the baby, known as recurrent respiratory papillomatosis
        (RRP).

        a.  Estimates of the incidence rate of RRP are imprecise; they
            range from 0.4-1.2 cases per 100,000 children.

        b.  The preventive value of cesarean delivery is unknown and,
            thus, should not be performed solely to prevent transmission
            of genital HPV to the newborn.

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F.  Risk factors consistently associated with genital HPV infection in
    women

    1.  Young age

    2.  Sexual behavior

        a.  Risk increases with increasing lifetime number of male sex
            partners

        b.  Early age of first sexual intercourse

    3.  Sexual behavior of male sex partners

        a.  Risk increases for women whose sex partners have had
            multiple sex partners.

    4.  Immune status

        a.  HPV is more likely to be detected in immune-suppressed women
            (e.g., HIV-infected persons, women on dialysis, and after
            kidney transplant).

G.  Risk factors less consistently associated with genital HPV infection
    in women

    1.  Smoking

    2.  Oral contraceptive use

    3.  Nutritional factors (poor nutrition)

    4.  Lack of circumcision of male partners

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H.  Risk factors associated with genital HPV infection in men

    1.  Greater lifetime number of sex partners

    2.  Greater number of recent sex partners

    3.  Being uncircumcised

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II. **Pathogenesis**

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A.  Virology

    1.  Key features of HPV

        a.  Double-stranded DNA virus that belongs to the Papovaviridae
            family

        b.  Small and non-enveloped virions

        c.  Over 100 characterized types

        d.  Number of recognized HPV types is gradually increasing as
            more types are identified and genetically characterized.

        e.  Genital types have specific tropism (affinity) for genital
            skin and mucosa.

        f.  Very limited animal models and no widely available system
            for in vitro cultivation

        g.  Infection is identified by the detection of HPV DNA or
            capsid protein.

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2.  HPV genotyping system

    a.  Types are distinguished by different DNA sequences (\>10%
        difference) at L1 capsid (surface) protein.

    b.  Genital HPV types are generally characterized in terms of their
        oncogenic potential (ability to cause cervical cancer).

        1.  Low-risk types

            i.  Associated with genital warts and benign or low-grade
                cervical cell changes (mild Pap test abnormalities).

            ii. Most visible genital warts are caused by HPV types 6 and
                11.

            iii. Recurrent respiratory papillomatosis, a rare condition,
                 is usually associated with HPV types 6 and 11.

        2.  High-risk types

            i.  Associated with low grade cervical cell changes,
                high-grade cervical cell changes that are precursors to
                cancer (moderate to severe Pap test abnormalities), and,
                in rare cases, anogenital (i.e., cervix, vulva, anus,
                and penis) cancers.

            ii. HPV types 16 and 18 account for more than half of HPV
                types found in anogenital cancers.

            iii. Most women infected with high-risk HPV types have
                 normal Pap test results and never develop precancerous
                 (high-grade) cervical cell changes or cervical cancer.

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B.  Pathology

    1.  Genital HPV infects squamous epithelium and stimulates cellular
        proliferation.

    2.  Affected cells display a broad spectrum of changes ranging from
        benign hyperplasia to dysplasia to invasive carcinoma.

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C.  Natural history of genital HPV infection

    1.  Most infections are transient, asymptomatic or subclinical, and
        have no clinical consequences in immunocompetent individuals.

    2.  The incubation period is unclear.

        a.  Probably 3 weeks to months for genital warts

        b.  Probably several months to years for cervical cellular
            abnormalities

    3.  The median duration of new cervical infections (measured by
        detection of HPV DNA) is 8 months but varies by HPV type.

        a.  70% of new infections clear within 1 year.

        b.  90% of new infections clear within 2 years.

        c.  The gradual development of an effective immune response is
            thought to be the likely mechanism for HPV DNA clearance.

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4.  Persistent infection is infection that is not cleared by the immune
    system and is characterized by persistently detectable HPV DNA.

    a.  HPV infection that persists is the most important risk factor
        for precancerous (high-grade) cervical cell changes and cervical
        cancer.

    b.  Factors associated with persistent infection include:

        1.  Older age

        2.  High-risk HPV types

        3.  Immune suppression

    c.  Most women with persistent HPV infection do not develop cervical
        cancer precursors or cervical cancer.

5.  It is unclear whether HPV infection that becomes non-detectable at
    mucosal surfaces has completely cleared or remains latent in basal
    cells with potential for later reactivation.

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III. **Clinical Manifestations and Sequelae**

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A.  In most cases genital HPV infection is transient and has no clinical
    manifestations or sequelae.

B.  Clinical manifestations of genital HPV infection include:

    1.  Genital warts

    2.  Cervical cell abnormalities

    3.  Anogenital squamous cell cancers

    4.  Recurrent respiratory papillomatosis

C.  The two most common clinically significant manifestations of genital
    HPV infection are:

    1.  Genital warts that are visualized without magnification

    2.  Cervical cell abnormalities that are detected by Pap test
        screening (with or without HPV DNA testing) or colposcopy

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D.  Genital warts

    1.  Genital warts have 4 morphologic types:

        a.  Condylomata acuminata

            1.  Cauliflower-like appearance

            2.  Skin-colored, pink, or hyperpigmented

            3.  May be keratotic on skin; generally non-keratinized on
                mucosal surfaces

        b.  Smooth papules: usually dome-shaped and skin-colored

        c.  Flat papules

            1.  Macular to slightly raised

            2.  Flesh-colored, with smooth surface

            3.  More commonly found on internal structures (i.e.,
                cervix), but also occur on external genitalia

        d.  Keratotic warts: thick horny layer resembling common warts
            or seborrheic keratosis

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2.  Location

    a.  Genital warts appear most commonly in areas of coital friction.

        1.  Men--penis, scrotum, urethral meatus, and perianal area

        2.  Women\--introitus, vulva, perineum, and perianal area

    b.  Less common genital warts sites:

        1.  Cervix and vaginal walls in women

        2.  Pubic area, upper thighs, or crural folds in men and women

    c.  Perianal warts do not necessarily imply anal intercourse, but
        may be secondary to autoinoculation, sexual activity other than
        intercourse, or spread from a nearby genital wart site.

    d.  Intra-anal warts are seen predominantly in patients who have had
        receptive anal intercourse.

    e.  HPV types causing genital warts can occasionally cause lesions
        on oral, upper respiratory, upper GI, and ocular locations.

    f.  Patients with visible warts can be infected simultaneously with
        multiple HPV types.

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3.  Symptoms

    a.  Genital warts usually cause no symptoms other than the warts
        themselves.

    b.  Vulvar warts can cause dyspareunia, pruritis, and burning
        discomfort.

    c.  Penile warts occasionally cause pruritis.

    d.  Urethral meatal warts occasionally cause hematuria or impairment
        of urinary stream.

    e.  Vaginal warts occasionally cause discharge, bleeding, or
        obstruction of birth canal (due to increased wart growth in
        pregnancy).

    f.  Perianal warts occasionally cause pain, bleeding on defecation,
        or pruritis.

    g.  Most patients have fewer than 10 genital warts, with total wart
        area of 0.5-1.0 cm^2^.

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4.  Duration

    a.  Genital warts may regress spontaneously or persist with or
        without proliferation.

    b.  Frequency of spontaneous regression is unclear. A few studies
        indicate a regression rate of 10%-30% within 3 months.

    c.  Persistence of infection occurs, but frequency and duration is
        unknown.

    d.  Recurrences after treatment are common (20%-50% recurrence rate
        at 3-6 months).

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5.  High-risk HPV types occasionally are found in visible genital warts
    and have been associated with external genital (i.e., vulvar,
    penile, and anal) squamous intraepithelial lesions (i.e., squamous
    cell carcinoma in situ, bowenoid papulosis, Erythroplasia of
    Queyrat, or Bowen's disease of the genitalia).

    a.  The most commonly recognized clinical manifestation of external
        genital squamous intraepithelial lesions (SIL) is bowenoid
        papulosis, dome-shaped or flat papules that are often
        hyperpigmented.

    b.  These lesions can sometimes be clinically indistinguishable from
        genital warts, but on biopsy demonstrate high-grade SIL.

    c.  They occur in what is usually macroscopically normal epithelium
        and mucosal tissue.

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6.  Genital warts in preadolescent children

    a.  May be due to sexual abuse and should prompt an evaluation for
        such.

    b.  May also result from vertical transmission, transmission of
        non-genital HPV types to genital surface, and possibly fomite
        transmission, although fomite transmission has never been
        documented.

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Image: Perianal warts

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Image: Vulvar warts

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Image: Penile warts

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Image: Intrameatal wart

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E.  Cervical cell abnormalities

    1.  Cervical cell abnormalities are usually subclinical.

        a.  They are detected by Pap test, colposcopy, or biopsy.

        b.  Magnification by colposcopy can enhance detection of
            cervical cell abnormalities; histology is used to confirm
            and stage cervical cell abnormalities.

    2.  Cervical cell abnormalities are usually caused by high-risk HPV
        types.

        a.  Most of the time high-risk HPV types do not cause any
            abnormalities.

        b.  Most women infected with high-risk HPV types have normal Pap
            test results.

    3.  Cervical cell abnormalities attributed to HPV often regress
        spontaneously without treatment.

    4.  Cervical cell abnormalities are classified based on whether the
        abnormality is likely to be a cervical cancer precursor.

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5.  The 2001 Bethesda System classifies cervical cellular abnormalities
    into one of several categories:

    a.  Atypical squamous cells (ASC) are cells that do not appear to be
        completely normal.

        1.  ASC--US---atypical squamous cells of undetermined
            significance. Sometimes the changes are related to HPV
            infection. ASC--US changes are usually mild abnormalities.

        2.  ASC--H---atypical squamous cells cannot exclude a high-grade
            squamous intraepithelial lesion. ASC--H changes are more
            likely to be precancerous abnormalities.

    b.  Low-grade squamous intraepithelial lesion (LSIL)\--generally a
        transient infection with a high-risk HPV type.

    c.  High-grade squamous intraepithelial lesion (HSIL)\--generally a
        persistent infection with a high-risk HPV type with a higher
        risk for progression to cervical cancer.

    d.  See the American Society for Colposcopy and Cervical Pathology
        Consensus Guidelines on Management of Women with Cytological
        Abnormalities for more information on the Bethesda
        Classification System.
        <http://www.asccp.org/consensus/cytological.shtml>

\[Slide 35\]

F.  Anogenital squamous cell cancers

    1.  HPV infection is causally associated with cervical cancer and
        probably other anogenital squamous cell cancers (e.g., anal,
        penile, vulvar, vaginal).

    2.  Over 99% of cervical cancers have HPV DNA detected within the
        tumor.

    3.  Persistent infection with a high-risk HPV type (e.g., infection
        which is not cleared by the immune system and which is
        characterized by persistently detectable HPV DNA) is necessary
        but not sufficient for the development of cervical cancer.

        a.  Other risk factors that increase risk of developing cervical
            cancer precursors and cervical cancers include:

            1.  Early age of first intercourse (16 years or younger)

            2.  History of multiple sex partners

            3.  Active or passive smoking

            4.  Long-term use of oral contraceptive

            5.  High number of pregnancies

            6.  Immune suppression

            7.  Co-infection with *Chlamydia trachomatis* or herpes
                simplex virus type-2

\[Slide 36\]

G.  Recurrent respiratory papillomatosis

    1.  HPV infections in infants and children may present as laryngeal
        papillomatosis, also known as juvenile onset recurrent
        respiratory papillomatosis (JORRP).

    2.  Respiratory papillomatosis is a rare condition, usually
        associated with HPV types 6 and 11.

\[Slide 37\]

IV. **Diagnosis of Genital Warts and Cervical Cellular Abnormalities**

\[Slides 38-39\]

A.  Diagnosis of genital warts

    1.  Diagnosis is usually made by visual inspection with bright
        light.

    2.  Diagnosis can be confirmed by biopsy.

        a.  Confirmation of diagnosis is needed when:

            1.  Diagnosis is uncertain.

            2.  Patient is immunocompromised.

            3.  Warts are pigmented, indurated, or fixed.

            4.  Lesions do not respond or worsen with standard
                treatment.

            5.  There is persistent ulceration or bleeding.

    3.  Use of type-specific HPV DNA tests for routine diagnosis and
        management of genital warts is not recommended.

    4.  Acetic acid evaluation (acetowhitening) of external genitalia is
        not recommended.

        a.  Low specificity (many false positives)

        b.  Acetowhitening will occur at sites of prior trauma or
            inflammation.

    5.  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 health care provider).

\[Slides 40-41\]

6.  Differential diagnosis of genital warts include:

    a.  Other infections

        1.  Condylomata lata--tend to be smoother, moist, more rounded,
            and darkfield-positive for *Treponema pallidum*. This is a
            manifestation of secondary syphilis and serologic tests for
            syphilis are positive.

        2.  Molluscum contagiosum--papules with central dimple, caused
            by a pox virus; rarely involves mucosal surfaces.

    b.  Acquired dermatologic conditions

        1.  Seborrheic keratosis

        2.  Lichen planus

        3.  Fibroepithelial polyp, adenoma

        4.  Melanocytic nevus

        5.  Neoplastic lesions

    c.  Normal anatomic variants

        1.  "Pink pearly penile papules"

        2.  Vestibular papillae (micropapillomatosis labialis)

        3.  Skin tags (acrochordons)

\[Slides 42-44\]

B.  Diagnosis of cervical cell abnormalities

    1.  Cytology (Pap test)

        a.  A useful screening test to detect cervical dysplasia (not
            HPV per se)

        b.  Provides indirect evidence of HPV because it detects
            squamous epithelial cell changes that are almost always due
            to HPV

        c.  No need for more frequent Pap test screening if external
            genital warts are present (assuming patient is receiving
            screening at intervals recommended by her health care
            provider).

        d.  The role of anal Pap test for cytologic screening is under
            investigation, especially among HIV-infected persons.

        e.  Limitations of Pap tests

            1.  Specimen adequacy--Pap test occasionally must be
                repeated when the laboratory judges the specimen
                unsatisfactory for evaluation.

            2.  Variable sensitivity (A review of the literature
                estimated that the sensitivity of a single Pap test was
                60%-80% for high-grade lesions, and even lower for
                low-grade lesions).

            3.  Technologies using liquid collection media (ThinPrep®
                Pap Test™, Autocyte Prep™) and computer-assisted reading
                may enhance sensitivity, but possibly reduce
                specificity.

    2.  Nucleic acid testing

        a.  A definitive diagnosis of HPV is based on detection of viral
            nucleic acid (DNA or RNA) or capsid protein.

        b.  A test that detects high-risk types of HPV DNA in cells
            scraped from the cervix is commercially available. The FDA
            has approved this test for two optional uses:

            1.  To triage women with atypical cells of undetermined
                significance (ASC-US) Pap test results, and

            2.  As an adjunct to the Pap test to screen for cervical
                cancer in women 30 years or older.

        c.  Use of HPV DNA testing for women with SIL Pap test results
            is unnecessary because the vast majority of women with SIL
            are infected with HPV.

            1.  Diagnosis of SIL requires additional techniques (e.g.
                cytology, colposcopy, and histopathology).

            2.  External genital warts are not an indication for HPV DNA
                testing.

    3.  Colposcopy

        a.  Indication for colposcopy is guided by physical exam and Pap
            test findings with or without HPV DNA test findings.

        b.  External genital warts are not an indication for cervical
            colposcopy.

    4.  Histology (biopsy)

        a.  Indications for cervical biopsy include:

            1.  Visible exophytic lesions on the cervix

            2.  Pap test with HSIL

            3.  Pap test with ASC-H or LSIL with colposcopic
                abnormalities

        b.  Indications for biopsy of external genitalia include:

            1.  Suspected bowenoid papulosis

            2.  Other atypical lesions where diagnosis is uncertain

    5.  For more information on guidelines for managing women with
        cervical cytologic abnormalities, refer to the 2001 Consensus
        Guidelines for the Management of Women with Cervical Cytologic
        Abnormalities.
        <http://www.asccp.org/consensus/cytological.shtml>

\[Slide 45\]

V.  **Patient Management/Treatment**

\[Slides 46-47\]

A.  General treatment of genital warts

    1.  Primary goal is removal of symptomatic warts.

    2.  If left untreated, visible genital warts may regress
        spontaneously or persist with or without proliferation.

    3.  In most patients, treatment can induce wart-free periods.

    4.  Currently available therapies may reduce, but probably do not
        eradicate, infectivity.

    5.  Effect of current treatment on future transmission is unclear.

    6.  No evidence that presence of genital warts or their treatment is
        associated with development of cervical cancer.

    7.  Because of uncertainty regarding the effect of treatment on
        future transmission and the possibility for spontaneous
        resolution, some patients may choose to forgo treatment and
        await spontaneous resolution.

    8.  Consider screening persons with newly diagnosed genital warts
        for other STDs (e.g., chlamydia, gonorrhea, HIV, syphilis).

\[Slides 48-49\]

B.  Treatment regimens

    1.  Patient-applied and provider-administered treatment regimens are
        available.

    2.  Providers should be knowledgeable about and have available at
        least one patient-applied and one provider-administered
        treatment.

C.  Choice of treatment should be guided by:

    1.  The preference of the patient

    2.  The available resources

    3.  The experience of the healthcare provider

D.  Factors that may influence selection of treatment include:

    1.  Wart size

    2.  Number of warts

    3.  Anatomic site of wart

    4.  Wart morphology

    5.  Patient preference

    6.  Cost of treatment

    7.  Convenience

    8.  Adverse effects

\[Slide 50\]

E.  Treatment response

    1.  Affected by:

        a.  Number, size, duration, and location of warts

        b.  Immune status (pregnancy, HIV infection)

        c.  In general, warts located on moist surfaces and in
            intertriginous areas respond better to topical treatment
            than do warts on drier surfaces.

    2.  Many patients require a course of therapy rather than a single
        treatment.

        a.  Non-surgical, locally destructive techniques may require
            multiple treatments.

        b.  Evaluate the risk-benefit ratio of treatment throughout the
            course of therapy to avoid over-treatment.

    3.  There is no evidence that any specific treatment is superior to
        any of the others.

        a.  No treatment is ideal for all patients or for all warts.

        b.  The use of locally developed and monitored treatment
            algorithms has been associated with improved clinical
            outcomes.

\[Slide 51\]

F.  Recurrence after treatment

    1.  Up to 2/3 of patients will experience recurrences of warts
        within 6-12 weeks of therapy; after 6 months most patients have
        clearance.

        a.  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.

        b.  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.

\[Slide 52\]

G.  Complications

    1.  Complications rarely occur if treatments for warts are employed
        properly.

        a.  Depressed or hypertrophic scars are uncommon but can occur,
            especially if the patient has had insufficient time to heal
            between treatments.

        b.  Rarely, treatment can result in disabling chronic pain
            syndromes (e.g., vulvodynia or hyperesthesia of the
            treatment site).

    2.  Patients should be warned that persistent hypopigmentation or
        hyperpigmentation are common with ablative modalities.

\[Slide 53\]

H.  CDC-recommended regimens for external genital warts (patient
    applied)

    1.  Podofilox 0.5% solution or gel (Condylox™)

        a.  Patients should apply podofilox solution with a cotton swab,
            or podofilox gel with a finger, to visible genital warts
            twice daily for 3 days, followed by 4 days of no therapy.

        b.  This cycle may be repeated as necessary for up to 4 cycles.

        c.  Total wart area treated should not exceed 10cm^2^, and a
            total volume of podofilox should be limited to 0.5mL per
            day.

        d.  If possible, the health care provider should apply the
            initial treatment to demonstrate the proper application
            technique and identify which warts should be treated.

        e.  *The safety of podofilox during pregnancy has not been
            established*.

> -OR-

2.  Imiquimod 5% cream (Aldara™)

    a.  Patients should apply imiquimod cream with a finger once daily
        at bedtime, 3 times a week for up to 16 weeks.

    b.  The treatment area should be washed with mild soap and water
        6-10 hours after the application.

    c.  *The safety of imiquimod during pregnancy has not been
        established.*

3.  Using patient-applied treatments

    a.  Provider should identify warts for treatment and teach patients
        how to apply substance.

    b.  Patient must be able to identify and reach warts to be treated.

    c.  Podofilox 0.5% solution or gel, an antimitotic drug that
        destroys warts, is relatively inexpensive, easy to use, and
        safe.

    d.  Most patients experience mild or moderate pain or local
        irritation after treatment with podofilox.

    e.  Imiquimod is a topically active immune enhancer that stimulates
        production of interferon and other cytokines.

    f.  Local inflammatory reactions are common with use of imiquimod;
        these reactions are usually mild to moderate.

    g.  Follow-up is not required, but may be useful several weeks into
        therapy to determine appropriateness of medication use and
        response to treatment.

\[Slide 54\]

I.  CDC-recommended regimens for external genital warts
    (provider-administered)

    1.  Cryotherapy with liquid nitrogen or cryoprobe

        a.  Repeat applications every 1 to 2 weeks.

        b.  May be used on internal or external warts and during
            pregnancy.

> -OR-

2.  Podophyllin resin 10%-25% in compound tincture of benzoin

    a.  Apply a small amount to each external wart and allow to air dry.

    b.  To avoid the possibility of problems with systemic absorption
        and toxicity, some experts recommend that application be limited
        to \< 0.5mL of podophyllin or \< 10cm^2^ of warts per session.

    c.  Some specialists suggest that the preparation area be thoroughly
        washed off 1 to 4 hours after application to reduce local
        irritation. Local irritation is common.

    d.  Repeat weekly if needed.

    e.  Potency, components, and contaminants in podophyllin are not
        standardized, and the shelf life is uncertain.

    f.  *The safety of podophyllin during pregnancy has not been
        established.*

> -OR-

3.  Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80%-90%

    a.  Apply a small amount only to warts and allow to air dry (white
        "frosting" develops).

    b.  If excess amount of acid is applied, powder the treated area
        with talc or sodium bicarbonate (i.e., baking soda), or with
        liquid soap preparations to remove unreacted acid.

    c.  Can be painful after application and may be caustic to
        unprotected skin around the warts (which can be protected by the
        application of Vaseline).

    d.  Repeat weekly if necessary.

    e.  Can be used on vaginal and anal warts as well as on external
        warts and during pregnancy.

> -OR-

4.  Surgical removal--tangential scissor excision, tangential shave
    excision, curettage, or electrosurgery

    a.  Surgical therapy is most beneficial for patients who have large
        numbers or areas of genital warts.

    b.  Can be used on accessible internal warts and during pregnancy.

\[Slide 55\]

J.  CDC-recommended alternative treatment regimens

    1.  Intralesional interferon

        a.  Systemic interferon is not effective.

        b.  Intralesional interferon has efficacy because of antiviral
            and/or immunostimulating effects.

        c.  Efficacy and recurrence rates of intralesional interferon
            are comparable to other treatment modalities.

        d.  Not recommended for routine use because of inconvenient
            routes of administration, frequent visits, and the
            association between its use and a high frequency of systemic
            adverse effects.

    2.  Laser surgery--costly, but may be useful in management of
        extensive warts or intraurethral warts, particularly for those
        patients who have not responded to other treatment regimens.

    3.  5FU currently is not recommended because of side effects.

\[Slide 56\]

K.  Treatment of exophytic cervical warts

    1.  High-grade squamous intraepithelial lesions must be excluded
        before treatment is initiated.

    2.  Management should include consultation with a specialist.

\[Slide 57\]

L.  CDC-recommended regimens for vaginal warts

> *Treat only if symptomatic, since most treatments also affect normal
> tissue and could cause scarring and pain.*

1.  Cryotherapy with liquid nitrogen

    a.  The use of a cryoprobe in the vagina is not recommended because
        of risk for vaginal perforation and fistula formation.

> -OR-

2.  TCA or BCA 80%-90% applied to warts

    a.  Apply small amount only to warts and allow to air dry (white
        "frosting" develops).

    b.  If an excess amount of acid is applied, powder the treated area
        with talc, sodium bicarbonate (i.e., baking soda), or with
        liquid soap preparations to remove unreacted acid.

    c.  Repeat weekly if needed.

\[Slide 58\]

M.  CDC-recommended regimens for urethral meatus warts

    1.  Cryotherapy with liquid nitrogen

> -OR-

2.  Podophyllin 10%-25%--in compound tincture of benzoin

    a.  Treatment area must be dry before contact with normal mucosa.

    b.  Repeat weekly if needed.

3.  Although data evaluating the use of podofilox and imiquimod for the
    treatment of distal meatal warts are limited, some specialists
    recommend their use in certain patients.

\[Slide 59\]

N.  Treatment of anal warts

    1.  Cryotherapy with liquid nitrogen

> -OR-

2.  TCA or BCA 80%-90% applied to warts

    a.  Apply small amount only to warts and allow to dry (white
        "frosting" develops).

    b.  If an excess amount of acid is applied, powder the treated area
        with talc, sodium bicarbonate (i.e., baking soda), or with
        liquid soap preparations to remove unreacted acid.

    c.  Repeat weekly if needed.

> -OR-

3.  Surgical removal

4.  Warts on the rectal mucosa should be managed in consultation with a
    specialist.

\[Slide 60\]

O.  CDC-recommended regimens for oral warts

    1.  Cryotherapy with liquid nitrogen

> -OR-

2.  Surgical removal

\[Slide 61\]

P.  Management of genital warts during pregnancy

    1.  Genital warts can proliferate and become more friable during
        pregnancy.

    2.  Cytotoxic agents (podophyllin, podofilox, imiquimod) should not
        be used.

    3.  Cryotherapy, TCA, BCA, and surgical removal may be used.

    4.  HPV types 6 and 11 can cause recurrent respiratory
        papillomatosis in infants and children. The route of
        transmission (i.e., transplacental, perinatal, or postnatal) is
        not completely understood.

    5.  The prevention value of cesarean delivery is unknown; thus,
        C-section should not be performed solely to prevent transmission
        to neonate.

        a.  Cesarean delivery may be indicated for women with genital
            warts if the pelvic outlet is obstructed or if vaginal
            delivery would result in excessive bleeding.

        b.  In rare instances, C-section may be necessary if extensive
            warts obstruct the birth canal or the risk of extensive
            bleeding during vaginal delivery is thought to be high.

\[Slide 62\]

Q.  Management of genital warts in immunodeficient patients

    1.  General considerations

        a.  Occur more frequently

        b.  More pronounced clinical manifestations and occurrence of
            atypical lesions such as oral warts

        c.  More resistant to conventional therapy

        d.  Recurrence of lesions after treatment more common

        e.  High-grade squamous intraepithelial lesions (HSIL) and
            invasive cancer arising in or resembling genital warts are
            more frequent in immunodeficient patients.

        f.  Role of warts (or irritated treatment sites) in HIV
            transmission unknown

    2.  Treatment considerations

        a.  Treatment unlikely to be effective due to high recurrence
            rate; therefore treat only if the patient is symptomatic.

        b.  Because HSIL and invasive cancer can occur in wart-like
            lesions, especially in the perianal area, lesions which are
            hyperpigmented or which persist despite treatment should be
            evaluated by biopsy.

\[Slide 63\]

R.  Pap test screening in immunodeficient patients

    1.  Immunodeficiency appears to accelerate intraepithelial neoplasia
        and invasive cancer.

    2.  Provide cervical Pap test screening every 6 months for 1 year,
        then annually for all HIV-infected women with or without genital
        warts.

    3.  The value of anal Pap tests and anoscopy in the absence of
        symptoms has not beem established, but is under investigation.

        a.  Because of the increased incidence of anal cancer in
            HIV-infected homosexual men, screening for anal cancer by
            cytology in this population is advocated by some
            specialists.

        b.  However, until more data about the natural history of anal
            SIL and treatment efficacy are available, such a screening
            approach is not recommended.

\[Slide 64\]

S.  Genital wart follow-up

    1.  Counsel patients to:

        a.  Watch for recurrences (most frequent in first 3 months after
            treatment)

        b.  Get regular Pap screening at intervals as recommended for
            women WITHOUT genital warts. The presence of genital warts
            is not an indication for increase in frequency of Pap test
            screening (assuming patient is receiving screening at
            intervals recommended by her health care provider) or for
            cervical colposcopy.

    2.  Follow-up evaluation is not mandatory after wart clearance, but
        provides an opportunity to:

        a.  Monitor or treat complications of therapy

        b.  Document the absence of warts

        c.  Reinforce patient education and counseling messages

    3.  Patients concerned about recurrences should be offered a
        follow-up evaluation 3 months after treatment.

\[Slide 65\]

T.  Treatment of cervical cell abnormalities

    1.  Detailed discussion of treatment of cervical cell abnormalities
        is beyond the scope of this educational offering.

    2.  For more information on managing women with cervical cell
        abnormalities, refer to:

        a.  CDC National Breast and Cervical Cancer Early Detection
            Program <http://www.cdc.gov/cancer/nbccedp/index.htm>

        b.  2001 Consensus Guidelines for the Management of Women with
            Cervical Cytologic Abnormalities
            <http://www.asccp.org/consensus/cytological.shtml>

\[Slide 66\]

VI. **Patient Counseling and Education**

\[Slide 67\]

A.  Patient counseling and education should include:

    1.  The nature of HPV infection

        a.  Genital HPV infection is common in sexually active adults.

        b.  Incubation period is variable, and it is often difficult to
            determine the source of infection.

        c.  Natural history of HPV infection is usually benign.

            1.  Low-risk genital HPV types are associated with mild Pap
                test abnormalities and genital warts.

            2.  High-risk types are associated with mild to severe Pap
                test abnormalities and, rarely, cancers of the cervix,
                vulva, anus, and penis.

            3.  Most women infected with high-risk HPV types have no Pap
                test abnormalities and do not develop cervical cancer.

        d.  Genital warts have a high recurrence rate after treatment.

\[Slide 68\]

2.  Transmission issues

    a.  Determining source of infection usually difficult; infection is
        not evidence of infidelity.

    b.  Recurrences usually are not re-infection.

    c.  Likelihood of transmission and duration of infectivity with or
        without treatment are unknown.

    d.  Abstinence and long-term mutual monogamy with an uninfected
        partner are the most effective options to prevent transmission.

    e.  The value of disclosing a past diagnosis of genital HPV
        infection to future partners is unclear, although candid
        discussions about past STD should be encouraged and attempted
        whenever possible.

\[Slide 69\]

3.  Risk reduction

    a.  Assess patient's behavior-change potential.

    b.  Develop individualized risk-reduction plans with the patient for
        lasting results.

    c.  Discuss prevention strategies such as abstinence, mutual
        monogamy with an uninfected partner, condoms, limiting number of
        sex partners, etc.

    d.  Effect of condoms in preventing transmission of genital HPV
        infection is not known.

        1.  HPV infections can occur in male and female genital areas
            that are not covered by a latex condom, as well as in areas
            that are covered.

        2.  While the effect of condoms in preventing HPV infection is
            unknown, condom use has been associated with lower rates of
            genital warts and cervical cancer, both HPV-associated
            diseases.

\[Slide 70\]

B.  HPV and cervical cancer prevention patient counseling and education
    resources

    1.  American Social Health Association, National HPV and Cervical
        Cancer Prevention Resource Center. Available at:
        <http://www.ashastd.org/hpvccrc/>

    2.  CDC Cervical Cancer Screening Fact Sheet
        <http://www.cdc.gov/cancer/nbccedp/cc_basic.htm>

    3.  National Cancer Institute Cervical Cancer Screening Information
        For Patients
        <http://www.nci.nih.gov/cancerinfo/pdq/screening/cervical/patient/>

    4.  American Society of Colposcopy and Cervical Cancer Pathology
        <http://www.asccp.org/pdfs/patient_edu/women_should_know.pdf>

\[Slide 71\]

VII. **Partner Management and Public Health Measures**

\[Slide 72\]

A.  Partner management for patients with genital warts

    1.  Sex partner examination is not necessary for management of
        genital warts because no data indicate that reinfection plays a
        role in recurrences.

    2.  Providing treatment solely for the purpose of preventing future
        transmission cannot be recommended because the value of
        treatment in reducing infectivity is not known.

    3.  The counseling of sex partners provides an opportunity for these
        partners to:

        a.  Learn about the implications of having a partner who has
            genital warts and about the potential for future disease
            transmission

        b.  Receive STD and Pap screening if necessary

\[Slide 73\]

B.  Cervical cancer screening

    1.  The key strategy to prevent cervical cancer is regular cervical
        cancer screening (Pap test screening) for all sexually active
        women.

    2.  New technologies including liquid-based cytology and testing for
        high-risk HPV types may offer potential advantages over
        conventional Pap testing.

    3.  Several organizations provide guidelines for cervical cancer
        screening (e.g., age to begin screening, screening intervals,
        special considerations), including the American Cancer Society
        (ACS), the American College of Obstetricians and Gynecologists
        (ACOG), and the U.S. Preventive Services Task Force (USPSTF).

        a.  CDC Cervical Cancer and Pap Test Information
            <http://www.cdc.gov/cancer/nbccedp/info-cc.htm>

        b.  National Cancer Institute Screening for Cervical Cancer
            Health Professional Information
            <http://www.nci.nih.gov/templates/doc_pdq.aspx?cdrid=62756>

        c.  American Cancer Society
            <http://www.guideline.gov/summary/summary.aspx?doc_id=3530&nbr=2756&string=Cervical+AND+Cancer+AND+Screening>

        d.  ACOG
            <http://www.acog.org/from_home/publications/press_releases/nr07-31-03-1.cfm?printerFriendly=yes>

        e.  U.S. Preventive Services Task Force Cervical Cancer
            Screening Recommendations
            <http://www.ahrq.gov/clinic/uspstf/uspscerv.htm>

        f.  American Society for Colposcopy and Cervical Pathology
            Consensus Guidelines on Management of Women with Cytological
            Abnormalities for more information on the Bethesda
            Classification System and on management of cervical cell
            abnormalities:
            <http://www.asccp.org/consensus/cytological.shtml>

\[Slide 74\]

C.  Reporting requirements

    1.  Genital HPV infection is not a reportable infection in any
        state.

    2.  Genital warts are reportable in some states.

    3.  Check with state or local health department for reporting
        requirements in your area.

\[Slide 75\]

D.  HPV vaccines

    1.  Several potential HPV vaccine approaches are under
        investigation. The most promising is the use of virus-like
        particles (VLPs), which preserve native conformations of viral
        proteins without presence of viral DNA.

        a.  In a recent double-blind, multi-center, randomized clinical
            trial, administration of a HPV type 16 (HPV-16) VLP vaccine
            reduced the incidence of HPV-16 infection and HPV-16-related
            cervical intraepithelial neoplasias.

        b.  HPV-16 is present in 50% of cervical cancers and high-grade
            cervical intraepithelial neoplasias and in 25% of low-grade
            cervical intraepithelial neoplasias.

**CASE STUDY**

\[Slide 77\]

Anne Drew is a 34-year-old woman who comes in stating that she wants to
get \"checked out\" because Jonathan, her sex partner, has small solid
\"bumps\" on the skin at the base of his penis. Jonathan told her that
he was diagnosed and treated for genital warts about a year ago, and his
health care provider told him they could recur.

**History**

-   No history of abnormal Pap tests and no history of STDs

-   Last Pap test was performed 4 months ago

-   Sexually active since age 16 with men and 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

\[Slide 78\]

1\. What should be included in Ms. Drew's evaluation?

Ms. Drew's evaluation should include a pelvic exam with a visual
inspection of genitalia. Diagnosis of genital warts is usually made by
visual inspection with bright light. If the diagnosis is uncertain, it
can be confirmed by biopsy.

Acetic acid evaluation of external genitalia is of limited value due to
its low specificity (many false positives) and is not recommended. Ms.
Drew had a normal Pap test four months ago. There is no need for more
frequent Pap tests when external genital warts are present.

HPV DNA testing is not recommended for diagnosis and management of
external genital warts.

\[Slide 79\]

**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

\[Slide 80\]

2\. What is the differential diagnosis for the papular genital lesions?

Correct responses include the following:

-   Secondary syphilis (Condylomata lata)

-   Molluscum contagiosum--caused by a pox virus

-   Genital warts--caused by HPV

-   Sebaceous glands--acquired dermatologic condition

-   Skin tags--acquired dermatologic condition

-   Melanocytic nevi--acquired dermatologic condition

-   Lichen planus--acquired dermatologic condition

3\. What is the **most likely** diagnosis based on history and physical
examination?

**Genital warts is the most likely diagnosis** due to her partner's
history of genital warts and the appearance of the lesions.

It is not a high priority to test for this diagnosis. The diagnosis of
genital warts is usually based on clinical appearance. No serologic test
is commercially available, nor would one be helpful in making the
diagnosis of genital warts since the presence of antibodies does not
indicate active infection.

If the lesions appear atypical (pigmented, fixed, indurated, or
ulcerated), then biopsy is indicated.

Secondary syphilis is not the most likely diagnosis, given the patient's
history and the general low incidence of syphilis. It is a high priority
to test for this diagnosis because the Condylomata lata of secondary
syphilis can mimic genital warts. A serologic test for syphilis should
be performed to evaluate for that possibility.

Molluscum contagiosum is not the most likely diagnosis because the
lesions are smooth dome-shaped papules with a characteristic central
umbilication (dimple). It is not a high priority to test for this
diagnosis.

Sebaceous glands is not the most likely diagnosis. Sebaceous glands are
normal anatomical structures that are generally smooth and
yellowish-white, and are usually not located on the perineum. It is not
a high priority to test for this diagnosis.

Skin tags is not the most likely diagnosis. Skin tags are normal
structures. While they may be somewhat pedunculated like warts, they
have a smooth instead of a rough surface. It is not a high priority to
test for this diagnosis.

Melanocytic nevi is not the most likely diagnosis. Melanocytic nevi are
hyperpigmented lesions. It is not a high priority to test for this
diagnosis.

Lichen planus is not the most likely diagnosis. Lichen planus tend to be
hyperpigmented lesions, and are violaceous and polygonal. It is not a
high priority to test for this diagnosis.

4\. Which laboratory tests should be ordered or performed?

Correct responses include the following:

-   Serologic test for syphilis (e.g., RPR -- STAT if available)

-   Test for *Chlamydia trachomatis*

-   Test for *Neisseria gonorrhoeae*

-   Counseling and testing for HIV

Screening for other STDs, including HIV, should be considered for all
persons newly diagnosed with HPV. A serologic test for syphilis should
be performed to rule out secondary syphilis.

\[Slide 81\]

**Patient Management**

The following genital warts management options are discussed with Ms.
Drew:

Patient-applied therapy

-   Podofilox 0.5% solution or gel (Condylox)

-   Imiquimod 5% cream (Aldara)

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

No intervention

\[Slide 82\]

5\. What is the effect of treatment on future transmission? What is the
possibility of recurrence after treatment?

The effect of treatment on future transmission is unknown. Because of
uncertainty about the effect of treatment on future transmission and the
possibility for spontaneous resolution, some patients may choose to
forgo treatment and await spontaneous resolution.

Recurrence of genital warts within the first several months after
treatment is common and usually indicates recurrence rather than
reinfection. Many patients require a course of therapy rather than a
single treatment. Treatment is labor intensive and non-surgical, locally
destructive techniques may require multiple treatments. Complications
rarely occur if treatments for warts are properly employed.

6\. What are appropriate counseling messages for Ms. Drew about genital
warts and HPV infection?

Correct responses include the following:

-   Genital HPV is a sexually transmitted viral infection which is
    common in sexually active adults.

-   The incubation period is variable and it is often difficult to
    determine the source of infection.

-   The 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, anus, and
    penis.

-   The majority of women infected with high-risk HPV types do not
    develop cervical cancer.

-   Genital warts have a high recurrence rate after treatment.

-   The value of disclosing a past diagnosis of genital HPV infection is
    unclear, although candid discussions about past STD should be
    encouraged and attempted whenever possible.

-   HPV infections can occur in male and female genital areas that are
    covered or protected by a latex condom, as well as in areas that are
    not covered.

-   While the effect of condoms in preventing HPV infection is unknown,
    condom use has been associated with lower rates of genital warts and
    cervical cancer, both HPV-associated diseases.

-   There is no need for her to have more frequent Pap test screenings
    after being diagnosed with genital warts (assuming she is receiving
    screening at intervals recommended by her health care provider),
    since genital warts are associated with low-risk HPV types, not the
    high-risk types associated with moderate to severe Pap test
    abnormalities and invasive cancer.

7\. What conditions could cause a substantial increase in the number and
size of Ms. Drew's genital warts?

Pregnancy and immunodeficiency can cause a substantial increase in the
number and size of genital warts.

**TEST QUESTIONS**

1.  It is estimated that at least \_\_\_of sexually active adults are
    infected with genital HPV during their lifetime.

    a.  10%

    b.  25%

    c.  40%

    d.  **50%**

2.  All of the following are true about transmission of genital HPV,
    **except**:

    a.  Transmission is associated with sexual activity.

    b.  **Transmission via fomites has been documented.**

    c.  Transmission can occur from asymptomatic and subclinical
        patients.

    d.  Transmission probably requires contact with viable HPV and
        microtrauma to skin/mucous membranes.

3.  HPV types \_\_ and \_\_\_ account for more than half of HPV types
    found in genital cancers.

    a.  6 and 11

    b.  6 and 18

    c.  **16 and 18**

    d.  11 and 16

4.  Genital HPV types are characterized in terms of their oncogenic
    potential (ability to cause cervical cancer).

    a.  **True**

    b.  False

5.  Most women infected with high-risk HPV types:

    a.  Develop cervical cancer

    b.  **Have normal Pap test results**

    c.  Have abnormal Pap test results

    d.  Have genital warts

6.  Which of the following is the most important risk factor associated
    with development of cervical cancer precursors (high-grade cervical
    cell changes) and cervical cancer?

    a.  Older age

    b.  High-risk HPV types

    c.  **Persistence of HPV infection**

    d.  Immunodeficiency

7.  If left untreated, visible warts may:

    a.  Resolve on their own

    b.  Remain unchanged

    c.  Increase in size and number

    d.  **Any of the above**

8.  Which factor should guide genital wart treatment?

    a.  The preference of the patient

    b.  The available resources

    c.  The experience of the health care provider

    d.  **All of the above**

9.  Which of the following is **not** a presentation of genital warts?

    a.  Condylomata acuminata

    b.  Smooth papules

    c.  Flat papules

    d.  Keratotic warts

    e.  **All of the above are presentations of genital warts**

10. Acetic acid evaluation of external genital warts is of limited value
    because:

    a.  It has low sensitivity (many false negatives).

    b.  **It has low specificity (many false positives).**

    c.  It is not cost effective.

    d.  All of the above

11. Manifestations of genital HPV infection include:

    a.  Genital warts

    b.  Cervical cell abnormalities

    c.  Anogenital squamous cell cancers

    d.  Respiratory papillomatosis

    e.  **All of the above**

12. Most genital HPV infections are transient and have no clinical
    manifestations or sequelae.

    a.  **True**

    b.  False

13. Which HPV types usually cause cervical cancer?

    a.  Low-risk types

    b.  **High-risk types**

    c.  Both low-risk and high-risk types

    d.  Neither low-risk nor high-risk types

14. Diagnosis of external genital warts is usually made by:

    a.  **Visual inspection**

    b.  Biopsy

    c.  Acetic acid evaluation

    d.  HPV DNA test

15. The FDA has approved the HPV DNA test for use in:

    a.  Cervical cancer screening for women under 30 years

    b.  **Triage of women with ASC-US Pap test results**

    c.  Triage of women with LSIL Pap test results

    d.  External genital wart diagnosis

16. Cervical cellular abnormalities are detected by which of the
    following?

    a.  Serologic test

    b.  **Pap test**

    c.  Wet mount

    d.  HPV DNA test

17. Which of the following statements is true about the treatment of
    genital warts?

    a.  In most patients treatment does not induce wart-free periods.

    b.  Current treatment decreases future transmission.

    c.  **The primary goal is removal of symptomatic warts.**

    d.  Available therapies eradicate infectivity.

18. Which of the following is a patient-applied treatment for external
    genital warts?

    a.  **Podofilox**

    b.  Podophyllin

    c.  Trichloroacetic acid (TCA)

    d.  Bichloroacetic acid (BCA)

19. Which of the following is a provider-administered treatment for
    external genital warts?

    a.  Cryotherapy with liquid nitrogen or cryoprobe

    b.  Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80%-90%

    c.  Podophyllin resin 10%-25% in compound tincture of benzoin

    d.  **All of the above**

20. All of the following external genital wart treatments may be used in
    pregnancy, **except**:

    a.  Surgical removal

    b.  Trichloroacetic acid (TCA) or biochloroacetic acid (BCA) 80%-90%

    c.  **Imiquimod 5% cream (Aldara)**

    d.  Cryotherapy

21. Which of the following is true of HPV infection in immunodeficient
    patients?

    a.  Genital warts occur more frequently.

    b.  Genital warts are more resistant to conventional therapy.

    c.  The occurrence of atypical lesions (e.g., oral warts) is more
        likely.

    d.  **All of the above**

22. Patient counseling and education should cover:

    a.  The nature of HPV infection

    b.  Transmission issues

    c.  Risk reduction

    d.  **All of the above**

23. All of the following are appropriate patient education messages
    about the nature of HPV infection **except**:

    a.  Genital HPV is a viral infection which is one of the most common
        STDs.

    b.  **High-risk HPV types are associated with external genital
        warts.**

    c.  Genital warts have a high recurrence rate after treatment.

    d.  The majority of women with high-risk HPV types do not develop
        cervical cancer.

24. Which of the following is correct about partner management for
    patients diagnosed with genital warts?

    a.  Sex partner examination is not necessary for management of
        genital warts because no data indicate that reinfection plays a
        role in recurrences.

    b.  Providing treatment solely for the purpose of preventing future
        transmission cannot be recommended because the value of
        treatment in reducing infectivity is not known.

    c.  The 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 future disease
        transmission and receive STD and Pap screening if necessary.

    d.  **All of the above**

25. The presence of genital warts is an indication for:

    a.  Change in Pap test frequency

    b.  Cervical colposcopy

    c.  Both of the above

    d.  **Neither of the above**

26. Which of the following actions should be considered for patients
    with newly diagnosed genital warts?

    a.  Screening of all current and former sex partners for genital
        warts

    b.  Immediate Pap smear, regardless of when last Pap screening was
        performed

    c.  **Screening for other STD (e.g., chlamydia, gonorrhea, HIV,
        syphilis)**

    d.  HPV DNA test

**RESOURCES**

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**Websites and Other Resources**

1.  CDC Division of STD Prevention: 
    [www.cdc.gov/std](http://www.cdc.gov/std)

2.  National Network of STD/HIV Prevention Training Centers: 
    <http://depts.washington.edu/nnptc/>

3.  2002 CDC STD Treatment Guidelines (including downloadable version
    for Palm devices):  <http://www.cdc.gov/STD/treatment/>

4.  CDC National STD Hotline:  800-227-8922 or 800-342-2437

    a.  En Español: 800-344-7432

    b.  TTY for the Deaf and Hard of Hearing: 800-243-7889

5.  CDC National Prevention Information Network (NPIN): 
    [www.cdcnpin.org](http://www.cdcnpin.org/)

6.  American Social Health Association, National HPV and Cervical Cancer
    Prevention Resource Center: <http://www.ashastd.org/hpvccrc/>

7.  CDC Cervical Cancer and Pap Test Information
    <http://www.cdc.gov/cancer/nbccedp/info-cc.htm>

8.  National Cancer Institute (NCI):
    [http://www.nci.nih.gov](http://www.nci.nih.gov/)

9.  U.S. Preventive Services Task Force Cervical Cancer Screening
    Recommendations: <http://www.ahrq.gov/clinic/uspstf/uspscerv.htm>

10. American College of Obstetrics and Gynecology:
    [http://www.acog.org](http://www.acog.org/)

11. American Society of Colposcopy and Cervical Pathology (ASCCP):
    [http://www.asccp.org](http://www.asccp.org/)

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