796

External Genital Warts: Report of the American Medical Association Consensus

Conference
Karl R. Beutner, Michael V. Reitano, Gary A. Richwald, From the University of California at San Francisco, San Francisco, the
Dorothy J. Wiley, and the AMA Expert Panel on Los Angeles County STD Program, the UCLA School of Public Health,
Los Angeles, California; the Riverview Medical Associates, New York,
External Genital Warts*
New York

A consensus process was undertaken to describe and evaluate current information and practice
regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs)
and their sex partners. This process developed a number of key statements that were based on
strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements
included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No

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one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of
men with EGWs are at increased risk for human papillomavirus – related cervical disease and, like
all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a
sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and
to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and
general information about sexual health and other sexually transmitted diseases.

External genital warts (EGWs) are visible by gross clinical risk types (e.g., 6, 11, 42, 43, and 44) and high-risk types (e.g.,
examination without instrumentation (e.g., colposcopy, anos- 16, 18, 31, 33, 35, 39, 45, 52, 55, 56, and 58) on the basis of
copy, and urethroscopy) and are one manifestation of human their association with anogenital cancers [6 – 15]. Most EGWs
papillomavirus (HPV) infection. Internal genital warts and dys- in immunocompetent patients are caused by HPV type 6 and
plasia, although important causes of disease and the subject of sometimes HPV type 11 [7, 12]. HPV types that cause EGWs
considerable attention in the medical literature, are not the can also cause visible warts in the vagina, on the uterine cervix,
focus of these consensus statements. and inside both the urethra and the anus [6, 10, 11, 16 – 19].
An estimated 24 million Americans are infected with HPV; In addition to genital warts, these HPV types have been associ-
between 500,000 and 1 million new cases of HPV-induced ated with conjunctival, nasal, oral, and laryngeal warts [20, 21].
genital warts occur annually [1, 2]. In 1995, EGWs and internal Most infections with low- and high-risk types occur without
genital warts accounted for ú240,000 initial visits to private evidence of EGWs, squamous intraepithelial lesions (SILs), or
physicians’ offices [2]. In the United States, 1% of sexually malignancy [22 – 25].
active men and women between the ages of 18 and 49 years A variety of approaches to the diagnosis and treatment of
are estimated to have EGWs [3]. The economic burden of HPV patients with EGWs have been developed, often along the lines
infection in the United States is substantial, estimated to exceed of individual medical specialties and subspecialties. In addition,
$3.8 billion in total costs in 1997 (excluding the cost of HPV- our understanding of the pathogenesis, assessment, and treat-
related cervical cancer). This cost represents more than one- ment of EGWs has increased in recent years. The consensus
third of the approximately $10 billion spent annually on com- statements in this article were developed to provide up-to-
mon sexually transmitted diseases (STDs; excluding HIV infec- date information for practitioners with the ultimate goal of
tion) and related syndromes [2]. improving patient care.
At least 70 HPV types are currently defined by their DNA
genotype on the basis of the alignments of the nucleotide se-
quences of the open reading frames L1, E6, and E7 [4, 5]. Methods
HPV types that infect the genital area can be divided into low- Eleven questions were outlined initially by the three panel
co-chairs (K. R. Beutner, G. A. Richwald, and M. V. Reitano)
in collaboration with medical education staff of the American
Received 1 December 1997; revised 27 May 1998.
Medical Association. The first set of questions was circulated
Grant support: The American Medical Association External Genital Wart to all panel members, and a consensus on 11 key questions
Consensus Development Processes and Conference were supported by an un- was achieved after three iterations of comment and revision.
restricted educational grant from 3-M Pharmaceuticals.
* Members of the American Medical Association Expert Panel on External
In addition, two key questions were expanded by the consensus
Genital Warts are listed at the end of the text. panel co-chairs, and a total of 15 key questions provided a
Reprints or correspondence: Dr. Karl R. Beutner, Solano Dermatology Asso- framework for the panel’s deliberations and the selection of
ciates, 127 Hospital Drive, Suite 204, Vallejo, California 94589.
data sources (table 1).
Clinical Infectious Diseases 1998;27:796–806
q 1998 by the Infectious Diseases Society of America. All rights reserved.
EGWs are treated by clinicians from a variety of disciplines.
1058–4838/98/2704–0024$03.00 Consequently, the panel of national leaders was multidiscipli-

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CID 1998;27 (October) External Genital Wart Consensus 797

nary, consisting of representatives from dermatology, family Information supporting the panel’s findings was rated using
practice, gynecology/obstetrics, internal medicine, infectious a two-tier, eight-category, quasi evidence – based method pre-
disease, pathology, pediatrics, student health, urology, epidemi- viously validated by the U.S. Preventive Services Task Force
ology, sociology, and health education. [26]. The strength and the quality of evidence supporting each
The consensus statements were formulated following an ex- recommendation were based on study design, efficacy, and
tensive review of the literature. MEDLINE and other proprie- clinical benefit. Whenever possible, the panel gave greater
tary databases were used for extensive subject, key-word, weight to study designs that were less subject to bias and
and title-word searches for the preceding 11 years. Select inferential error. Where there was insufficient evidence, ratings
MEDLINE searches were conducted for articles published be- were based on the clinical experience and judgment of the
fore 1985. Data sources not found through database searches consensus panel.
included abstract booklets, conference proceedings, and refer- Recommendations with strong evidence for substantial clinical
ences identified from bibliographies of pertinent articles and benefit to support the proposition were rated as A; those with
books, companies, or manufacturers of therapeutic agents. moderate or strong evidence that showed only limited clinical

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Preliminary position statements corresponding to the key benefit were rated as B. When the evidence for efficacy was
questions were presented for detailed review and revision by insufficient to support an affirmative or negative recommendation
the expert panel at a 3-day, closed meeting in January 1997. or evidence for efficacy did not outweigh the adverse conse-
Small working groups and plenary session discussions were quences of use, the panel rated the proposition as C or optional.
used to prepare written statements that were reviewed repeat- When evidence showed a moderate lack of efficacy or a moderate
edly by the entire expert panel. Two additional revisions of the association with adverse outcomes, a recommendation was rated
statements were conducted by correspondence with the full as D, generally not to be offered. When there was good evidence
expert panel. The final statement was approved by all panel supporting poor efficacy or a strong association with adverse
members in May 1997. outcomes, the panel rated the recommendation as E. The quality
of evidence was rated in three categories (I, II, and III). The
Table 1. Key questions on EGWs of the American Medical Associa- categories were judged and ranked on the basis of evidence from
tion Consensus Conference. one or more properly randomized, controlled clinical trials (I), one
or more well-designed observational studies (i.e., nonrandomized
Evaluation and diagnosis clinical trial; cohort, case-control, or time series study; or noncon-
What is the basis for diagnosis of EGWs and perianal warts?
trolled experimental trials) (II), and opinions of respected authori-
What are the indications for biopsy or other tests, such as detection of
HPV DNA, to confirm the diagnosis of EGWs? ties that were based on clinical experience, descriptive studies,
Therapy and reports of expert committees (III) (table 2).
What are the goals of therapy and acceptable therapeutic modalities for
the treatment of EGWs?
What follow-up is recommended once EGWs are cleared? Consensus
Screening: women
Should women with EGWs undergo cervical cancer screening? Clinical Diagnosis
Should female sex partners of patients for whom EGWs or HPV-
associated cervical disease are diagnosed be evaluated for EGWs? EGWs are visible warts that occur in the genital area,
Should female sex partners of male patients with EGWs undergo cervical (e.g., penis, scrotum, perineum, vulva, perianal area, pubic
cancer screening?
area, upper thighs, and crural folds) [29, 59 – 62]. They ap-
Screening: men
Should male sex partners of patients for whom EGWs or HPV-associated pear as discrete lesions or may coalesce into confluent
cervical disease are diagnosed be evaluated for EGWs? plaques [30, 36, 63]. The clinical diagnosis of EGWs in
When is anal cancer screening indicated? the immunocompetent patient by physical examination is
Children and adolescents reliable on the basis of a good correlation between physical
How should children with lesions suspected of being EGWs be evaluated
findings and histological studies [31, 62, 64 – 67]. Clinical
to confirm or rule out the diagnosis of EGWs?
How should children suspected of being sexually abused be evaluated for inspection, without the aid of instrumentation (i.e., colpos-
EGWs? copy, anoscopy, and urethroscopy), is sufficient to diagnose
How should children with EGWs be evaluated for suspected child sexual most EGWs. EGWs are frequently multifocal, with one or
abuse? more lesions on one anatomic site (e.g., vulva), or multicen-
Patient counseling
tric, with lesions on disparate anatomic sites (e.g., perineum
How should patients be counseled about infectivity, transmission, risk
reduction, and disclosure? and cervix) [30, 31, 35, 36, 61 – 70]. Thus, it is important to
What gaps currently exist in patient education on EGWs and how should examine the entire lower genital tract for the presence of
these gaps be addressed? multicentric visible warts before treatment.
Health care provider education Bright light and magnification with a loop, hand lens, or
What gaps currently exist in health care provider education of EGWs and
colposcope may assist in diagnosis. Evaluation for visible in-
how should these gaps be addressed?
traanal warts by anoscopy is recommended for men and women
NOTE. EGW Å external genital wart; HPV Å human papillomavirus. with recurrent perianal warts and/or a history of receptive anal

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798 Beutner et al. CID 1998;27 (October)

Table 2. Key statements, strength of recommendations, quality of evidence, and supporting materials
of the American Medical Association Consensus Conference.

Strength of Quality of
Variable, recommendation recommendation evidence [Reference(s)]

Diagnosis
Clinical examination is sufficient to diagnose A III
most EGWs.
Mild acetic acid soaking should not be used D II [27, 28]
routinely to screen patients for EGWs.
Biopsy is seldom necessary to accurately D III
diagnose EGWs.
Detection and typing of HPV are not E III [29 – 33]
currently recommended for diagnosis or

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management of EGWs.
Treatment
The goal of treatment for EGWs is the A III
removal of symptomatic warts.
Standard therapies for EGWs can eventually A I and III [34]
remove most warts, although no one
treatment is ideal for all warts or all
patients.
Clinicians should be knowledgeable about C III
and have available to them at least one
patient-applied treatment and one health
care provider – administered therapy.
Screening
Sex partners of patients with EGWs should B III [27, 35 – 41]
be evaluated for EGWs, screened for other
STDs, and receive educational
information.
The value of referring sex partners of C III [28, 39, 42, 43]
women with HPV-related cervical SILs
for EGW screening is unknown.
Women with EGWs should undergo cervical A II [44 – 47]
cytological screening.
Patients with external perianal warts or a C III [48 – 55]
history of receptive anal intercourse may
be at increased risk for anal high-grade
SILs, but routine screening is not
currently recommended.
Children and adolescents
The presence of EGWs in minors is rare and A III [32, 56 – 58]
requires initiation of sexual abuse
evaluation.

NOTE. A Å strong evidence for substantial clinical benefit to support the proposition; B Å moderate or strong
evidence that showed only limited clinical benefit; C Å evidence for efficacy is insufficient to support an affirmative
or negative recommendation or evidence for efficacy did not outweigh the adverse consequences of use (or optional);
D Å moderate lack of efficacy or a moderate association with adverse outcomes (generally not to be offered); E Å
good evidence supporting poor efficacy or a strong association with adverse outcomes; EGW Å external genital wart;
HPV Å human papillomavirus; STD Å sexually transmitted disease; SIL Å squamous intraepithelial lesion; I Å one
or more properly randomized, controlled clinical trials; II Å one or more well-designed observational studies; III Å
opinions of respected authorities that were based on clinical experience, descriptive studies, and reports of expert
committees.

intercourse. If urinary symptoms of terminal hematuria or an papules [71, 73, 74]; keratotic genital warts that have a thick,
abnormal urinary stream are present, the distal urethra and horny layer and may resemble a common wart or a seborrheic
meatus should be visually examined, and a referral for urethros- keratosis; and flat-topped papules that appear macular to
copy should be considered. slightly raised [71, 75, 76].
There are four morphological types of EGWs: condylomata The morphological type is generally associated with one of
acuminata that are cauliflower-shaped [36, 71, 72]; papular the two major types of skin in the genital area: fully keratinized
warts that are dome-shaped (usually skin-colored) 1- to 4-mm hair-bearing or non-hair-bearing skin and partially keratinized,

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CID 1998;27 (October) External Genital Wart Consensus 799

moist, and non-hair-bearing skin. Keratotic and smooth papular addition, biopsy may be considered when individual warts are
EGWs occur on fully keratinized skin, condylomata acuminata ú1 cm, which raises the possibility of a Buschke-Löwenstein
occur most commonly on moist surfaces, and flat-topped papu- tumor; the diagnosis is in doubt; lesions do not respond to a
lar EGWs can occur on either surface. standard course of therapy; lesions are pigmented, thus sug-
gesting the possibility of bowenoid papulosis or high-grade
SILs [85, 86]; and if disease worsens during therapy, which
Differential Diagnosis
can occur when papulosquamous conditions such as lichen
The differential diagnosis of EGWs includes two types of planus or psoriasis are treated with ablative therapeutic modal-
morphological lesions: papules and flat erythematous lesions ities. Biopsy may be indicated more often for immunosup-
[77 – 82]. Genital papules include normal anatomic structures: pressed patients because high-grade SILs are more common in
pearly penile papules, vestibular papillae, and sebaceous glands these patients than in immunocompetent patients and may be
or glands of Tyson. Acquired papules include the following: less often distinguishable clinically from EGWs.
molluscum contagiosum, Crohn’s disease, seborrheic keratosis, Detection and typing of HPV have no proven benefit in the

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lichen planus, lichen nitidus, skin tags, melanocytic nevi, pseu- diagnosis or management of EGWs. Thus, routine detection
doverrucous papules, and condylomata. Vulvar intraepithelial and typing of HPV is not recommended currently for diagnosis
neoplasia, formerly called vulvar carcinoma in situ, is a papular or management of EGWs.
pruritic lesion that may appear as a skin-colored, hypopig-
mented or hyperpigmented, warty lesion. Bowenoid papulosis
is a condition marked by the presence of dome-shaped or flat- Cervical Cancer Screening
topped papules (usually 1 – 5 mm in diameter) that may have As with other sexually active women, all women with EGWs
a hyperpigmented or bluish hue and may be clinically indistin- and those reporting contact with a sex partner with EGWs
guishable from the papular form of EGWs [83 – 86]. Histologi- should have their history of recent cervical cancer screening
cal examination of these papules shows high-grade intraepithe- documented [44]. Women with EGWs should undergo annual
lial neoplasia; bowenoid papulosis is usually associated with cervical cytological screening. After three negative annual
HPV type 16 infection [87, 88] but can also be associated with screening tests, women may be screened at intervals recom-
other high-risk types of HPV. A very rare manifestation of mended by reported guidelines that are supported by their
infection due to low-risk types of HPV is the Buschke- health care provider [44].
Löwenstein tumor, a form of verrucous squamous cell carci-
noma [85, 89].
Flat erythematous lesions include psoriasis, seborrheic der- Anal Screening
matitis, balanitis circinata associated with Reiter’s syndrome,
high-grade SILs, Bowen’s disease, erythroplasia of Queyrat Patients with perianal warts (i.e., those visible on inspection
(Bowen’s disease on the glans penis or basaloid [flat] carci- without use of an anoscope), patients who are HIV-seroposi-
noma on the vulva), vulvar intraepithelial neoplasia, and squa- tive, and patients with a history of receptive anal intercourse
mous cell carcinoma [77, 80, 82, 85, 86]. may be at increased risk of anal high-grade SILs [44, 50].
There is no direct evidence that anal high-grade SILs progress
to invasive anal cancer. By analogy with cervical cancer, it is
Additional Diagnostic Approaches possible that identification and treatment of anal high-grade
Bright light and magnification may assist in the diagnosis SILs will reduce the incidence of anal cancer [49]. One recent
of smaller EGWs. The value of using dilute (3% – 5%) acetic study showed that anal cytology was useful in identifying pa-
acid solutions (i.e., ‘‘the acetowhite test’’) has not been estab- tients with intraanal SILs [51]. However, more data are needed
lished, and the positive predictive value of this test for EGWs on the natural history of intraanal high-grade SILs, the perfor-
is low [27, 28]. Some clinicians find that acetic acid soaking mance of screening tests for intraanal high-grade SILs, and the
is a useful adjunct in diagnosing visible lesions suspected of efficacy of therapy for these lesions in preventing anal cancer
being EGWs, particularly flat-topped papular warts [90]. How- before firm recommendations can be made on routine screening
ever, acetic acid soaking is not recommended for screening of the anal canal in patients with EGWs and/or a history of
individuals for EGWs, since acetowhite areas often are not receptive anal intercourse.
EGWs [27, 28]. When the acetowhite test is used, care must
be exercised to avoid overdiagnosis of EGWs, as acetowhite
Screening for Other STDs
change occurs with many other conditions.
When the diagnosis is in doubt, referral to a practitioner Patients with EGWs should be evaluated for other STDs,
experienced in the diagnosis of EGWs should be considered. many of which may be asymptomatic [1, 2]. This evaluation
Biopsy in cases of clinically diagnosed EGWs seldom is may include testing for chlamydial infection, gonorrhea, syphi-
needed. However, biopsy should be performed when lesions lis, vaginitis, hepatitis B, and HIV infection. The need to test
are indurated, fixed to underlying structures, or ulcerated. In for these STDs is greatest among sexually active patients under

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800 Beutner et al. CID 1998;27 (October)

the age of 25, a group accounting for two-thirds of all reported as a 10%–25% suspension of resin in benzoin tincture [66, 70,
STDs in the United States [1, 2]. 74, 102–105]. TCA and BCA are caustic agents that destroy
warts by chemical coagulation of proteins.
Simple office surgery also can remove warts and often
Treatment
promptly provides a wart-free state. Once local anesthesia is
The primary goal of treatment of EGWs is to eliminate warts achieved, EGWs can be physically removed and destroyed by
that cause physical or psychological symptoms. Physically, EGWs curettage, electrosurgery, or tangential excision with a pair of
often are asymptomatic but can be painful, friable, or pruritic. fine scissors or a scalpel. These simple procedures are applica-
Emotionally, EGWs may be stigmatizing socially and a reminder ble to patients with limited, average, or extensive EGWs.
of an STD. Treatment can induce wart-free periods, but the under- A therapeutic implant consisting of 5-fluorouracil, bovine
lying viral infection may or may not persist. The elimination of collagen, and epinephrine injected beneath the wart has been
warts may or may not decrease infectivity since EGWs may not shown to be effective [106, 107]. The mechanism of action of
represent the entire viral burden (e.g., internal sites and clinically this implant is probably due to the antimetabolic effect of

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normal skin may act as reservoirs for infection). 5-fluorouracil. IFNs have antiviral, antitumor, and immune en-
If left untreated, EGWs may resolve on their own, remain hancing activity. Intralesional IFN has been shown to be effec-
unchanged, or increase in size or number, and rarely, if ever, tive; however, systemic administration has proved to be inef-
EGWs may progress to cancer [6–12, 16, 17, 91–94]. Treatment fective for EGWs [29, 30, 37, 38, 59, 68, 92, 102].
should be tailored to the patient’s disease and needs as well as Concurrent use of multiple therapeutic modalities on a single
to available resources. At the present, no one treatment is ideal wart is not recommended as routine treatment. Because of
for all patients or all warts. Treatments can be classified as either unproven efficacy, significant toxicity, and teratogenicity, pa-
patient-applied or health care provider–administered (table 3). tient-applied 5-fluorouracil cream is not recommended for rou-
Clinicians who treat patients with EGWs should be knowledge- tine treatment of EGWs.
able about and have available at least one patient-applied treatment Treatments for EGWs frequently disrupt skin integrity to
and one health care provider–administered therapy. varying degrees and for varying durations. Consequently, heal-
Patient-applied treatments include podofilox solution and gel ing open sores (i.e., erosions and, rarely, ulcers) may increase
and imiquimod cream. Health care provider – administered a sexually active patient’s risk of contracting or transmitting
treatments can be divided into topical therapy (e.g., cryother- other STDs.
apy, trichloroacetic acid [TCA], bichloroacetic acid [BCA], The average patient has a relatively small number of EGWs
and podophyllin resin), simple office surgery (e.g., curettage, that can eventually be eliminated with most treatment modal-
electrosurgery, scissor excision, and laser vaporization), and ities. Health care provider – administered topical treatments sel-
injectable therapy (e.g., IFN and 5-fluorouracil/epinephrine gel dom work promptly in patients with large or extensive areas
implant). of EGWs. These patients should have surgical treatment or a
IFN, 5-fluorouracil/epinephrine gel implant, imiquimod, and patient-applied therapy to at least debulk their EGWs. Patients
podofilox have been systematically and prospectively evaluated with limited disease (i.e., one to five warts) may benefit most
in multicenter, placebo-controlled clinical trials. Other thera- from simple office surgery, cryotherapy, or other health care
peutic modalities have been compared with alternative treat- provider – administered treatments. Additional details on treat-
ments or no treatment but have not been subjected to rigorous ment are available in the Centers for Disease Control and Pre-
placebo-controlled study [34]. vention’s STD Treatment Guidelines [107a].
Podofilox solution or gel (0.5%) and imiquimod cream (5%) Many patients require a course of therapy rather than a single
are patient-applied treatments. Podofilox is an antimitotic treatment. Studies have not systematically evaluated the pa-
agent, purified from podophyllum resin, that can destroy warts tient-related and health care provider – related factors that in-
[97, 98]. Imiquimod is a topically active immune enhancer that fluence the selection of therapy. Factors that may influence
stimulates production of IFN and other cytokines [99, 100]. treatment selection include the following: size, morphology,
Patients must be able to identify and reach the warts and to and number of warts; anatomic site; patient’s preference; pa-
follow application instructions to successfully use these patient- tient’s age and cognitive ability; and clinician’s training and
applied therapies. experience (table 4). The development of a comprehensive
Cryotherapy destroys warts by cryocytolysis. Inadequate train- treatment algorithm for patients with EGWs would be desirable
ing in the use of cryotherapy frequently results in over- or under- but is very difficult because of a number of reasons. Different
treatment of warts, thus leading to poor efficacy and/or increased specialties have effective but fundamentally different ap-
complications. Although the use of an injected local or topical proaches to treatment. Many health care providers either do
anesthetic is not required, it can facilitate cryotherapy, particularly not have all therapeutic modalities available to them or are not
when a large number or a large area of warts is present. Podophyl- trained in their use. Disease presentation and patient prefer-
lum resin contains a number of antimitotic compounds including ences vary widely.
podofilox (i.e., podophyllotoxin) and the two mutagens [101] For health care provider – administered topical therapies, ex-
quercetin and kaempherol. Podophyllin is usually compounded perts recommend that if there has not been significant improve-

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CID 1998;27 (October) External Genital Wart Consensus 801

Table 3. Summary of patient-applied and health care provider – administered treatments for EGWs.

Therapy Advantage(s) and disadvantage(s) Contraindication(s) and pitfall(s)

Recommended treatment*
Patient-applied
Podofilox solution and gel Patient applied, results are dependent on patient ú10 cm2 of wart area; safety for use in
compliance pregnancy not known
Imiquimod cream Patient-applied immune enhancer Safety for use in pregnancy not known
Health care provider – administered
Cryotherapy Effective for moist and dry warts, pain (can be reduced Over- or underapplication
by use of an anesthetic), safety and efficacy highly
dependent on health care provider’s skills and
experience
Podophyllin Most effective on moist warts, relatively simple to use, Pregnancy, large wart area,

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unknown shelf-life, may contain mutagens, variable overapplication
concentration of active components, limited value for
dry warts
TCA or BCA Inexpensive, most effective for moist warts, relatively Large area of friable warts, low
simple to use and safe during pregnancy, limited value viscosity results in spreading if
for dry warts overapplied
Office surgery
Curettage, electrosurgery, and Prompt wart-free state, results depend on health care
scissor excision provider’s skill and training, requires equipment, longer
clinic visit, local anesthetic is mandatory
Alternative treatment†
Intralesional
5-FU/epinephrine implant Pain on injection, multiple visits Pregnancy and breast-feeding
IFN Immune enhancer, long time (weeks to months) to Pregnancy, transplant patients,
clearance, many (9 – 16) visits, systemic reactions, psychiatric disease
recommended dose limits treatment to patient with a
small number of warts
Surgery
Laser Prompt wart-free state, may require general anesthesia, Improper power settings damage
results and safety dependent on health care provider’s normal tissues [95, 96]
skill [95, 96]

NOTE. BCA Å bichloroacetic acid; EGW Å external genital wart; 5-FU Å 5-fluorouracil; TCA Å trichloroacetic acid.
* For routine or first-line treatments.
†
Should be reserved for patients for whom other multiple recommended therapies failed or who are not appropriate candidates for other treatments.

ment after three treatment sessions or if complete clearance since treatment will decrease the risk of obstetrical complica-
has not occurred after six treatment sessions, treatment should tions with delivery. Appropriate treatments for EGWs during
be changed or the patient should be referred. For patient-applied pregnancy include TCA or BCA, cryotherapy, surgical re-
therapeutic modalities, treatment beyond the manufacturer’s moval, and laser ablation.
recommendations is not advisable. The risk-benefit ratio should
be evaluated throughout the course of therapy to avoid overtre-
atment and a therapeutic course worse than the disease itself. Posttreatment Follow-up
Persistent hypo- or hyperpigmentation is a common compli-
The benefit, frequency, interval, and type of follow-up care
cation of ablative therapeutic modalities. Depressed or hyper-
necessary after treatment of EGWs has not been studied. When
trophic scars occur rarely [52, 108]. Ablative treatment can
appropriate, follow-up visits may be scheduled to document
result in disabling chronic pain syndrome (e.g., vulvadynia) or
treatment outcomes (e.g., a wart-free state), manage complica-
hypesthesia at the treatment site [109]. Some experts report
tions of therapy, and evaluate for recurrence. A follow-up visit
that patients with fair complexions seem to be the most suscep-
to document a wart-free state should be made available but is
tible to chronic pain syndromes following treatment of EGWs.
not necessary in all cases. Follow-up evaluation can also pro-
vide the opportunity for education and counseling of patients.
Pregnancy
The need to monitor for complications of therapy will vary
greatly on the basis of the patient’s experience and cognitive
Treatment during pregnancy requires some special consider- ability, the number and location of warts, and the treatment
ations. EGWs should be treated during pregnancy, especially modality used. Patients concerned about recurrence should be

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802 Beutner et al. CID 1998;27 (October)

Table 4. Some factors that influence the selection of treatment for The specific benefit of evaluating sex partners of women
EGWs. with HPV-related cervical SILs for EGWs is not known [110].
Although as many as one-half of male sex partners of women
Age
Safety and efficacy of treatments for EGWs have not been studied in with cervical SILs may have evidence of genital HPV infection,
pediatric populations. relatively few have EGWs. It is unclear whether treatment of
When treating, attention should be paid to avoiding and controling pain men with evidence of genital HPV infection influences the
associated with treatment. natural history of their female sex partner’s cervical disease
Requiring a parent or guardian to apply a treatment that may be painful is
[27, 39, 42, 110]. There is little information available currently
questionable.
Variations in the rate of psychosocial development in adolescence should about the health effects of HPV-related cervical disease on
be taken into account (i.e., cognitive ability to understand and female sex partners of women with HPV infection [43]. Just
carry out any treatment program, particularly patient-applied as in cervical cancer screening for women with EGWs, women
therapy). who are sex partners of patients with EGWs should undergo
Pregnancy and lactation
cytological screening for cervical cancer at intervals recom-

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Safety of podofilox, imiquimod, and IFN in pregnancy is not known.
5-Fluorouracil is a teratogen. mended by reported guidelines [44]. The benefit of evaluating
Disease prevention: wart size, wart number, anatomic location, circumcision male sex partners of men with EGWs is not known, although
status (men), and epithelial presentation (fully keratinized vs. an association between a history of self-reported receptive anal
partially keratinized skin) intercourse and perianal EGWs has been reported [108].
Wart size and count: In general, health care provider – administered topical
treatments are not ideal for large areas of warts, although they
may have a debulking effect. Infants, Children, and Adolescents
Warts on moist (partially keratinized) surfaces and intertriginous areas
As in adults, diagnosis of EGWs in infants, children, and
appear to respond better to topical treatments than do warts on dry
(fully keratinized) surfaces and open areas. adolescents is based primarily on physical examination. The
Aggressive ablative or surgical therapy should be avoided over the differential diagnosis and indications for biopsy, the acetowhite
clitoris, glans penis, urinary meatus, prepuce, and preputial cavity test, and detection and typing of HPV DNA are analogous to
in uncircumcised men. those for the adult population. Young children and adolescents
Patient preferences and characteristics
may suffer emotional trauma when genital procedures are per-
Tolerance of pain
Preference for health care provider or patient application formed. Thus, examinations and treatments should be per-
Duration of treatment and/or number of visits formed by knowledgeable practitioners after age-appropriate
Cost of treatment counseling and attention to pain relief.
Cognitive ability EGWs are rare in the general pediatric population. Although
Ability to accurately identify and physically reach EGWs
some children appear to acquire EGWs in a nonabusive man-
Health care provider preferences and characteristics
Clinical training and experience ner, the prevalence of confirmed sexual abuse is high among
Fiscal and physical resources verbal children with EGWs [32, 53, 56]. The diagnosis of
Scheduling limitations EGWs in a child requires that the clinician report suspected
Immunologic status child abuse. The act of reporting does not imply that sexual
Use of immunomodulators (i.e., imiquimod and IFN) should be avoided
abuse is confirmed but is a means to begin an evaluation process
in allograft recipients, other immunosuppressed patients, and
perhaps pregnant patients. that may or may not confirm sexual abuse. State laws regarding
Immunocompromised patients may have lower response and higher the reporting of suspected child abuse or neglect should be
recurrence rates. observed. The clinician who fails to follow state law guidelines
has the burden of ensuring the subsequent safety of the child.
NOTE. EGW Å external genital wart.
The American Academy of Pediatrics and the American Profes-
sional Society on the Abuse of Children have reported recom-
mended standards for the evaluation of children for sexual
offered an evaluation 3 months after successful treatment since
abuse and STDs [56 – 58, 111].
most recurrences occur during this period. In immunosup-
Caring for adolescent patients is frequently complicated by
pressed patients, recurrences of EGWs are much more com-
a conflict between two ethical concerns: the adolescent’s right
mon, and periodic follow-up evaluation for recurrence of
to confidentiality and the need to investigate and protect the
EGWs may be necessary.
minor from potential abuse. Adolescents should be interviewed
privately. Clinicians should explore whether forced sexual con-
Sex Partner Evaluation tact and physical contact have occurred and evaluate the safety
of the home.
The benefit of evaluating sex partners of patients with EGWs
has not been carefully studied. Evaluation does, however, pro-
Patient Counseling
vide an opportunity for education of sex partners about identi-
fication and prevention of EGWs, genital examination for Health care providers have a responsibility to inform patients
EGWs, and, where appropriate, screening for other STDs. that EGWs are caused by infection with HPV, which is sexually

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CID 1998;27 (October) External Genital Wart Consensus 803

transmitted in most cases. Because HPV infection has neither infection, understanding the risk of recurrence or reinfection,
a cure nor a well-defined natural history and is associated with disclosing their infection to current and future sex partners,
the social stigma of an STD, addressing patient concerns about and protecting sex partners from infection [112]. It may be
the potential chronic nature of the infection can be challenging helpful to explain that a current or recent sex partner was not
and time-consuming. Accordingly, clinicians should use writ- necessarily the source of infection nor do EGWs necessarily
ten educational materials or referrals to other sources of patient reflect infidelity in a monogamous relationship. Patients should
information. Ideally, patients should be counseled about three be informed that following successful treatment, recurrences
broad areas: the nature of EGWs, treatment protocols, and are common and may not represent reinfection.
anticipatory guidance about the potential impact of EGWs on Patient education should include that while treatment may
their lives. reduce infectivity, HPV infection may persist after treatment
and, therefore, future partners may be at risk. There is insuffi-
Nature of EGWs cient evidence to evaluate the effectiveness of condoms in
preventing transmission of HPV infection. Nonetheless, pa-

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Given the gaps in scientific understanding of HPV, EGWs tients should be counseled about the general guidelines for
can be explained to patients in terms of ‘‘knowns’’ and ‘‘un- prevention of STDs, including the proven effectiveness of con-
knowns.’’ Knowns include the following: HPV infection is a doms in preventing many infections such as HIV infection and
viral infection that may or may not persist, HPV infection is gonorrhea. There is no consensus at present on the necessity
most often sexually transmitted, and the HPV types likely to of fully disclosing one’s HPV infection to sex partners. How-
cause EGWs are not the same types associated with an in- ever, legal precedent from litigation on genital herpes may
creased risk of cervical cancer and generally do not cause argue for disclosure, and some patients will benefit from guid-
infections that pose a serious long-term health risk. Women ance in this area. The need for regular Pap smears and screening
also can be assured that EGWs do not jeopardize their chances for other STDs also should be discussed.
of giving birth to a healthy child.
Unknowns largely reflect uncertainty or controversy over
the natural history of HPV infection. Although warts can be Conclusions
eliminated, underlying viral infection may or may not persist. A diverse group of experts was able to reach a consensus
The duration of infectivity after treatment of EGWs is uncer- on a number of key issues related to the diagnosis, treatment,
tain. The high prevalence, long incubation period, and potential management, and education of patients with EGWs and their
for asymptomatic transmission of HPV infection often preclude sex partners. Some of these positions are supported by strong
tracing an infection to a source sex partner. The source sex evidence in the literature, while others are reasonable supposi-
partner may or may not know that they have EGWs or HPV tions based on the experience of experts in the field.
infection. Sexually active individuals with or without EGWs In the process of reaching a consensus, important areas for
can be infected with and transmit low- and high-risk types of future research were identified, particularly the need to know
HPV. when patients are infectious and the impact of treatment on
infectivity. Comparative trials of available therapies are needed
Treatment Options to firmly establish the relative efficacy and effectiveness, safety,
Although available treatments are often safe and effective, and recurrence rates. It would be valuable to know the preva-
clinicians should explain, whenever possible, the rationale for lence of other STDs in patients with EGWs and the impact of
treating vs. not treating EGWs and the rates of treatment failure EGWs on the acquisition and transmission of other STDs. Pa-
and recurrence. Warts can recur after treatment. However, the tient self-diagnosis of EGWs is a comparatively basic fact for
recurrence rates after successful treatment with common thera- which the specificity and sensitivity need to be established. A
peutic modalities have not been well characterized. Treatments better understanding of the route and frequency of nonsexual
can be characterized as removal of EGWs and possibly reduc- transmission of genital HPV infection in children, adolescents,
tion of infectivity. Clinicians should explain the adverse effects and sexually active adults is needed.
of the available treatments, their costs, and the influence that Education about EGWs and other STDs needs to be ex-
special considerations (e.g., age and impaired immune func- panded in medical school curricula and in the ongoing educa-
tion) might have on treatment and efficacy (table 3). Patients tion of clinicians in training and practice (e.g., residencies,
should be counseled about the time necessary to heal after specialty organizations, and their accrediting bodies). Clini-
treatment and the potential need for abstinence or use of barrier cians who care for patients with EGWs should counsel patients
protection until the tissue is fully healed. about all aspects of their diagnosis, including infectivity, trans-
mission and recurrence of EGWs, and the relationship of HPV
infection to cancers.
Anticipatory Guidance
Patients with EGWs receive care from a wide range of clini-
A survey on genital HPV infection revealed that the major cal disciplines in a variety of clinical settings. It is hoped
concerns of patients include determining the source of their that development of these consensus statements will be the

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804 Beutner et al. CID 1998;27 (October)

beginning of a process that will increase clinicians’ and pa- Control and Prevention, U.S. Department of Health Services, Public
Health Service, 1996.
tients’ understanding of this STD. The strength of this article
3. Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human
rests on a multidisciplinary consensus. Complementary educa- papillomavirus infection. Epidemiol Rev 1988; 10:122 – 63.
tional materials for health care providers and patients need to 4. de Villiers EM. Human pathogenic papillomavirus types. An update. Curr
be developed to elevate the quality of care and education pro- Top Microbiol Immunol 1994; 186:1 – 12.
vided to patients with EGWs and their sex partners. 5. Delius H, Hofmann B. Primer-directed sequencing of human papillomavi-
rus types. Curr Top Microbiol Immunol 1994; 186:13 – 31.
6. Durst M, Gissmann L, Ikenberg H, et al. A papillomavirus DNA from a
Acknowledgments cervical carcinoma and its prevalence in cancer biopsy samples from
different geographic regions. Proc Natl Acad Sci USA 1983; 80:
This article is an effort to collate the extensive work in the field 3812 – 5.
of external genital warts of many investigators to whom the authors 7. Gissmann L, zur Hausen H. Partial characterization of viral DNA from
human genital warts (condylomata acuminata). Int J Cancer 1980; 25:
are indebted. Special appreciation is due to the following American
605 – 9.
Medical Association staff members for their assistance in the re-

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8. Gissmann L, deVilliers EM, zur Hausen H. Analysis of human genital
view of the literature and manuscript preparation: Mary Jane Brakl warts (condylomata acuminata) and other genital tumors for human
and R. Mark Evans, Ph.D. papillomavirus type 6 DNA. Int J Cancer 1982; 29:143 – 6.
9. Gissmann L. Human papillomavirus DNA in genital tumours. IARC Sci
Publ 1984; 63:405 – 11.
Members of the American Medical Association Expert Panel on 10. Koutsky LA, Holmes KK, Critchlow CW, et al. A cohort study of the
External Genital Warts risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to
papillomavirus infection. N Engl J Med 1992; 327:1272 – 8.
Karl R. Beutner, M.D., Ph.D. (cochair), University of California, 11. Lorincz AT, Reid R, Jenson AB, et al. Human papillomavirus infection
San Francisco; Michael V. Reitano, M.D. (cochair), The Riverview of the cervix. Relative risk associations of 15 common anogenital
Medical Associates, New York, New York; Gary A. Richwald, types. Obstet Gynecol 1992; 79:328 – 37.
M.D., M.P.H. (cochair), Los Angeles County STD Program, Los 12. Gissmann L, Boshart M, Durst M, et al. Presence of human papillomavi-
Angeles; David Baker, M.D., State University of New York, Ston- rus in genital tumors. J Invest Dermatol 1984; 83:26s – 8s.
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