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Penile warts: an update on their evaluation and management
Alexander KC Leung MBBS, FRCPC, FRCP (UK and Irel), FRCPCH, FAAP1, Benjamin Barankin MD, FRCPC2,
Kin Fon Leong MBBS, MRCPCH3, Kam Lun Hon MD, FAAP, FCCM4
1Department of Pediatrics, The University of Calgary, Alberta Children’s Hospital, Calgary, Alberta, Canada;
2Toronto Dermatology Centre, Toronto, Ontario, Canada; 3Pediatric Institute, Kuala Lumpur General Hospital,
Kuala Lumpur, Malaysia; 4Department of Pediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong

Abstract administered therapies include podophyllin, cryotherapy,

Background: Penile warts are the most common sexually bichloroacetic or trichloroacetic acid, oral cimetidine, surgical
transmitted disease in males. Clinicians should be familiar excision, electrocautery, and carbon dioxide laser therapy.
with the proper evaluation and management of this common Patients who do not respond to first-line treatments may
condition. respond to other therapies or a combination of treatment
modalities. Second-line therapies include topical/intralesional/
Objective: To provide an update on the current understanding, intravenous cidofovir, topical 5-fluorouracil, and topical ingenol
evaluation, and management of penile warts. mebutate.
Methods: A PubMed search was completed in Clinical Queries Conclusion: No single treatment has been shown to be
using the key terms ‘penile warts’ and ‘genital warts’. The search consistently superior to other treatment modalities. The choice
strategy included meta-analyses, randomized controlled trials, of the treatment method should depend on the physician’s
clinical trials, observational studies, and reviews. comfort level with the various treatment options, the patient’s
Results: Penile warts are caused by human papillomavirus preference and tolerability of treatment, and the number
(HPV), notably HPV-6 and HPV-11. Penile warts typically and severity of lesions. The comparative efficacy, ease of
present as asymptomatic papules or plaques. Lesions may be administration, adverse effects, cost, and availability of the
filiform, exophytic, papillomatous, verrucous, hyperkeratotic, treatment modality should also be taken into consideration.
cerebriform, fungating, or cauliflower-like. Approximately one- Keywords: bichloroacetic/trichloroacetic acid, cimetidine,
third of penile warts regress without treatment and the average cryotherapy, electrocautery, human papillomavirus, imiquimod,
duration prior to resolution is approximately 9 months. Active laser, podofilox, podophyllin, sinecatechins, surgery.
treatment is preferable to watchful observation to speed up
clearance of the lesions and to assuage fears of transmission Citation
and autoinoculation. Patient-administered therapies include Leung AKC, Barankin B, Leong KF, Hon KL. Penile warts: an update
podofilox (0.5%) solution or gel, imiquimod 3.75 or 5% cream, on their evaluation and management. Drugs in Context 2018; 7:
and sinecatechins (polypheron E) 15% ointment. Clinician- 212563. DOI: 10.7573/dic.212563

Introduction meta-analyses, randomized controlled trials, clinical trials,

observation studies, and reviews.
Penile warts are the most common sexually transmitted disease
in males and are caused by human papillomavirus (HPV).1–3
Penile warts typically present as soft flesh-colored to brown Epidemiology
papules or plaques on the penile shaft and glans penis.4
Worldwide, HPV infection is the most common sexually
To provide an update on the current understanding, evaluation, transmitted disease.4 In the United States, 50–75% of sexually
and management of penile warts, a narrative review was active individuals have been infected with genital HPV at some
conducted based on a PubMed search using the key terms point during their lifetime.4,5 Infection with genital HPV does
‘penile warts’ and ‘genital warts’. The search strategy included not mean that an individual will develop genital warts.5 It is

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estimated that 0.5–5% of sexually active young male adults

have genital warts upon physical examination.6–9 The peak age Figure 1.  Penile warts manifesting as small,
is between 25 and 29 years.7,10 Generally, approximately 75% of discrete, soft, smooth, flesh-colored,
males who have sexual contact with a partner who has genital dome-shaped papules.
warts develop penile warts within 8 months.8

Etiopathogenesis
HPV is a nonenveloped, capsid, double-stranded
deoxyribonucleic acid (DNA) virus belonging to the
Papillomavirus genus of the Papillomaviridae family and infects
only humans.11 The virus has an eight kilobase circular genome
that encodes eight genes, including the genes for the two
encapsulating structural proteins, namely L1 and L2.11 The
virus-like particle containing L1 is used in the manufacturing of
HPV vaccines.11 L1 and L2 mediate HPV infectivity.11
More than 200 HPV types have been isolated thus far, of which
more than 100 HPV genotypes have been sequenced.4,11,12
More than 40 HPV types can be transmitted sexually.4,11,12
HPV can be divided into high-risk or low-risk types based
on their risk for cancer. Approximately 90% of genital warts
are caused by the low-risk types HPV-6 and/or HPV-11.2–4,13 Figure 2.  Penile warts manifesting as multiple,
small, discrete, soft, smooth, flesh-
HPV-1, HPV-2, HPV-3, HPV-4, HPV-16, HPV-18, HPV-40, HPV-42,
colored, dome-shaped papules in
HPV-43, HPV-44, HPV-54, HPV-70, HPV-72, and HPV-81 account
clusters.
for the rest.14 It is possible to be infected with different HPV
types at the same time.8 In adults, genital HPV infection is
predominately transmitted by sexual intercourse and, less
commonly, by oral sex, skin-to-skin transmission, and fomites.8
In children, HPV infection may result from sexual abuse,
vertical transmission, autoinoculation, hetero-inoculation
(nonsexual contact with a caregiver), and transmission via
fomites.1,15 The HPV virus invades cells in the basal layer of the
epidermis through micro-abrasions in the skin or mucosa.13
The incubation period for genital infection varies from 3 weeks
to 8 months, with an average of 2–4 months.12,16,17 The disease
is more common in individuals with the following factors:
immunodeficiency, unprotected sexual intercourse, multiple
sexual partners, sexual partner with multiple sexual partners,
prior sexually transmitted disease, sexual intercourse at an
early age, shorter time interval between meeting with a new
partner and engaging in sexual activity, non-circumcision, and
sulcus.3,8,13 Penile warts typically present as small, discrete, soft,
smoking.3,18–21 Moisture, maceration, trauma, and epithelial
smooth, pearly, dome-shaped papules at onset.3,7,14 Lesions
defects in the penile area are other predisposing factors.3
can occur separately (Figure 1) or in clusters (Figure 2).8 They
can be pedunculated or sessile. With time, the papules may
Histopathology coalesce into plaques.14 Lesions may be filiform, exophytic,
papillomatous, verrucous, hyperkeratotic, cerebriform,
Histological findings include papillomatosis, focal parakeratosis, fungating, or cauliflower-like (Figures 3–5).3,7,22 The color is
marked acanthosis, multiple vacuolated koilocytes, vascular variable and may be flesh-colored, pink, erythematous, brown,
distension, and coarse keratohyalin granules.4,17 violaceous, or hyperpigmented.4,23

Clinical manifestations Diagnosis

Penile warts are usually asymptomatic and rarely pruritic or The diagnosis is mainly clinical, based on the history and
painful.3,8,13 Penile warts are usually located on the frenulum, physical findings. Dermoscopy and in vivo reflectance confocal
glans penis, inner surface of the prepuce, and coronal microscopy help to increase the diagnostic accuracy.24 The

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Figure 3.  Penile warts manifesting as multiple Figure 5.  Penile warts manifesting as papillomas
verrucous papules and plaques. on the penile shaft.

Figure 4.  Penile warts that are cauliflower-like. Differential diagnosis

Differential diagnosis includes pearly penile papules, Fordyce
spots, acrochordons, condylomata lata of syphilis, molluscum
contagiosum, granuloma annulare, lichen nitidus, lichen
planus, seborrheic keratosis, epidermal nevus, lymphangioma
circumscriptum, lymphogranuloma venereum, scabies,
syringomas, traumatic neuromas, schwannomas, bowenoid
papulosis, and squamous cell carcinoma.7

Pearly penile papules typically present as asymptomatic,

small, smooth, soft, yellowish, pearly white, or flesh-colored,
conical- or dome-shaped papules 1–4 mm in diameter
(Figure 6).27 The lesions are usually uniform in size and shape
and are symmetrically distributed.27 Typically, the papules
occur in single, double, or multiple rows circumferentially
around the corona and sulcus of the glans penis. The papules
tend to be more prominent on the dorsum of the corona and
less prominent towards the frenulum.27
morphological features may vary from finger-like, knob-like,
Fordyce spots are enlarged sebaceous glands. On the glans
to mosaic-like pattern.24–26 Among the vascular features,
and shaft of the penis, Fordyce spots appear as asymptomatic,
glomerular, hairpin, and dotted vessels are commonly seen.26
isolated or grouped, discrete, creamy yellow, smooth papules
Papillomatosis is a constant feature.4 Some authors suggest
1–2 mm in diameter (Figure 7).28–30 On the penile shaft, these
the use of acetowhite test to aid the diagnosis of penile warts.
papules are more obvious during penile erection or when the
While the sensitivity of acetowhite test is high for hyperplastic
foreskin is stretched.28,30 A thick chalky or cheesy material can
penile warts, the sensitivity is low for other types of penile
sometimes be expressed by squeezing the lesion.28
warts and subclinically infected areas. Skin biopsy is seldom
warranted but should be considered for atypical features Acrochordons, also known as skin tags, are soft, flesh-colored
(e.g., atypical pigmentation, induration, fixation to to dark brown, sessile or pedunculated skin growths with
underlying structures, hard consistency, ulceration, or a smooth contour (Figure 8).31,32 Occasionally, the lesions
bleeding), when the diagnosis is in doubt or for warts may be hyperkeratotic or have a warty appearance.33 Most
recalcitrant to various treatment modalities. Although some acrochordons are 2–5 mm in diameter, although often larger
authors suggest HPV DNA test to show the type of HPV that in the groin.32 They can appear in almost any part of the body
may affect the risk of malignant transformation, HPV typing but are more frequently seen on the neck and intertriginous
is generally not recommended for routine diagnosis and not areas.31,32 When they occur on the penile area, they can mimic
easily obtained.13 penile warts.

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Figure 6.  Pearly penile papules presenting as Figure 8.  Acrochordons presenting as soft, flesh-
flesh-colored papules circumferentially colored skin growths with a smooth
distributed on the corona of the glans contour.
penis.

Figure 9.  Molluscum contagiosum presents as

discrete, smooth, dome-shaped, pearly
white papules on the penile shaft.

Figure 7.  Fordyce spots presenting as discrete,

creamy yellow, smooth papules.

sites of the genitals and perineum.36 A nonpruritic, diffuse,

symmetrical, maculopapular rash on the trunk, palms, and
soles is characteristic of secondary syphilis.34 Systemic
manifestations include headache, fatigue, pharyngitis, myalgia,
and arthralgia.34 Alopecia, erythematous, or leukoplakic lesions
on the oral mucosa and generalized lymphadenopathy may be
present.36
Typically, molluscum contagiosum presents as discrete, smooth,
firm, dome-shaped, yellow, pearly white or skin-colored, waxy
papules with characteristic central umbilication (Figures 9
and 10).37–39 In the pediatric age group, lesions are most
Condylomata lata or condyloma latum are cutaneous lesions commonly seen on the trunk and intertriginous areas, whereas
of secondary syphilis caused by the spirochete, Treponema in adults, lesions are more commonly seen on the lower
pallidum.34,35 Clinically, condylomata lata manifest as moist, abdomen, upper thighs, and genital area (Figure 9).39 The size
gray-white, velvety, flat-topped or cauliflower-like, broad of lesions ranges from 1 to 5 mm in diameter and the number
papules or plaques.36 They tend to develop in warm, moist of lesions is usually less than 20.38,39

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Figure 10. Examination of a molluscum Figure 12. Lichen planus presenting as purple,

contagiosum lesion under a planar, polygonal papules on the glans
dermatoscope shows a discrete dome- penis.
shaped papule with central umbilication.

Figure 13. Seborrheic keratosis presenting as a

well-demarcated, oval, brown plaque
with a ‘stuck on’ warty appearance.

Figure 11. Lichen nitidus presenting as multiple

discrete, flat-topped, fleshed-colored
papules on the penile shaft.

Lichen nitidus is a chronic inflammatory dermatosis

characterized by numerous, asymptomatic, discrete, flat-
topped, flesh-colored, shiny, pinhead- to pinpoint-sized
papules (Figure 11).43,44 The abdomen, chest, extremities, and
penis are sites of predilection.43–45 The lesions are usually
arranged in groups.43
Granuloma annulare is a benign, self-limited inflammatory
Cutaneous lichen planus is a chronic inflammatory dermatosis
disease of the dermis and subcutaneous tissue. The condition
characterized by six Ps: pruritic, purple (violaceous), planar
is characterized by asymptomatic, firm, brown violaceous,
(flat-topped), polygonal, papules/plaques that affect the skin
erythematous, or flesh-colored papules, typically arranged
(Figure 12).46 Sites of predilection include the flexor aspects of
in an annular, circinate configuration.40 As the condition
the wrists, dorsa of hands, trunk, shins, ankles, and glans penis.47
progresses, central involution may be noted.40 The ring of
Approximately 25% of the lesions occur on the genitalia.47
papules often becomes coalescent to form an annular plaque.
Granuloma annulare typically involves the extensor surfaces of Seborrheic keratosis typically presents as an asymptomatic,
the distal extremities but may also involve the shaft and glans well-demarcated, round or oval, brown plaque with a ‘stuck
of the penis.41,42 on’ warty appearance (Figure 13).48 Often, lesions may appear

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Figure 14. Lymphangioma circumscriptum Figure 15. Human scabies presenting as

presenting as clusters of small firm dark- erythematous papules, which are
red blisters with warty surface on the intensely pruritic.
distal penis, resembling frog spawn.

Lymphogranuloma venereum is a sexually transmitted

disease caused by Chlamydia trachomatis.34 The condition is
characterized by a transient painless genital papule and, less
commonly, an erosion, ulcer, or pustule followed by inguinal
and/or femoral lymphadenopathy with a characteristic ‘groove
shiny and oily and, hence, the misnomer ‘seborrheic’ (greasy) sign’ known as buboes.34,53
keratosis.48 Sites of predilection include the face, chest, back,
Human scabies, caused by the parasite mite Sarcoptes scabiei
and extremities. Occurrence on the penis is rare but has been
var hominis, is characterized by burrows, erythematous papular
reported.49 HPV is found in approximately 70% of cases of
eruption, and intense pruritus (often worse at night).54 The
seborrheic keratosis in the genital area versus 5% in nongenital
papules, caused by a hypersensitivity reaction to the mite, are
areas.49
erythematous and usually 1–2 mm in diameter (Figure 15).54
An epidermal nevus is a hamartoma arising from embryonic
Typically, syringomas present as asymptomatic, small, soft
ectoderm that differentiates into keratinocytes, apocrine
to firm, flesh- to tan-colored papules usually 1–3 mm in
glands, eccrine glands, hair follicles, and sebaceous glands. The
diameter.55 The lesions are usually found in the periorbital
classic lesion is a solitary, asymptomatic, well-circumscribed
areas and on the upper cheeks.55 However, syringomas may
plaque that follows Blaschko lines. The onset is usually within
appear on the penis and buttocks. When located on the penis,
the first year of life. The color varies from flesh to yellow to
syringomas may be mistaken for penile warts.
brown. The lesion may thicken and become more verrucous
with time. Traumatic neuromas are nerve sheath tumors in which the
ratio of axons to Schwann cell fascicles is approximately
Lymphangioma circumscriptum is a benign saccular dilatation
equal.56,57 The condition results from regenerative proliferation
of the cutaneous and subcutaneous lymphatics.50 The
of traumatized or injured nerve fibers.56,57 Penile traumatic
condition is characterized by clusters of vesicles resembling
neuromas may result from trauma to the penis, such as
frog spawn (Figure 14). The color depends on the content:
circumcision or penile dorsal neurotomy to treat premature
whitish, yellow, or light tan coloration is due to color of the
ejaculation.56–59 Clinically, penile traumatic neuromas present
lymph fluid while reddish or blue color is due to the presence
with skin-colored or erythematous papules or nodules on the
of erythrocytes in the lymph fluid as a result of hemorrhage.51
glans or penile shaft.56–59
The vesicles may undergo verrucous changes and have a warty
appearance.50 Sites of predilection include the extremities and, Schwannomas are neoplasms originated from Schwann
less commonly, the genitalia.52 cells.60 A penile schwannoma typically presents as a solitary,

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asymptomatic, slow-growing nodule on the dorsal aspect of with penile lesions, and alleviate symptoms (e.g., pruritus, pain,
the penile shaft.60,61 or bleeding).3,7,77 Penile warts that persist for more than 2 years
are less likely to resolve spontaneously and active treatment
Bowenoid papulosis is a premalignant focal intraepidermal
should be seriously considered.14 Sexual partners should be
dysplasia that typically manifests as multiple red to brown
offered informational counseling. Testing for other sexually
papules or plaques in the anogenital area, such as the penis.62
transmitted diseases is advisable.
The condition corresponds to in situ squamous cell carcinoma.
Progression to invasive squamous cell carcinoma occurs in Active treatments may be mechanical, chemical,
2–3% of cases.62 immunomodulatory, and antiviral.80 Head-to-head
Typically, squamous cell carcinoma of the penis presents as a comparisons of available modalities are scarce. Effectiveness
nodule, ulcer, or erythematous lesion.63 The lesion may appear varies among treatment modalities. Thus far, no single
warty, leukoplakic, or sclerotic.63,64 The most common site is treatment has been shown to be consistently superior to
the glans penis, followed by the prepuce and shaft.63 other treatment modalities. The choice of the treatment
method should depend on the physician’s comfort level
with the various treatment options, the patient’s preference
Complications and tolerability of treatment, and the number and severity
Penile warts can be a cause of significant anxiety or distress to of lesions. The comparative efficacy, ease of administration,
the patient and his sexual partner because of their disfiguring adverse effects, cost, and availability of the treatment modality
appearance and transmissibility, stigmatization, concerns about should also be taken into consideration. In general, patient-
future fertility and risk of cancer, and their association with administered therapies are less effective compared with
other sexually transmitted diseases.65,66 It is estimated that 20– clinician-administered ones.6
34% of affected patients have concomitant sexually transmitted
diseases.17 Affected patients often experience guilt, feelings of Patient-administered therapies
shame, low self-esteem, and angst.67 Individuals with penile
Patient-administered therapies include podofilox (0.5%)
warts have higher rates of sexual dysfunction, depression, and
solution or gel, imiquimod 3.75 or 5% cream, and sinecatechins
anxiety when compared with the normal population.65,68 The
(polypheron E) 15% ointment.13,80,81 Podofilox (0.5%) solution or
condition can have negative psychosocial effects on the patient
gel is derived from podophyllotoxin, a plant resin that works by
and may adversely affect quality of life.66,69–72 Large exophytic
disrupting microtubules during cell cycle replication, arresting
lesions may bleed, cause urethral obstruction, and interfere
mitosis, and causing tissue necrosis, and has been shown
with sexual intercourse.7,14,73 Malignant transformation is rare
efficacious in the treatment of penile warts.79,82 Podofilox
except in immunocompromised individuals.74,75 Individuals
(0.5%) solution or gel is applied topically twice a day for 3
with penile warts are at increased risk for anogenital, head,
consecutive days per week and can be applied at home.7 The
and neck cancers as a result of coinfection with high-risk HPV
weekly cycle can be repeated up to four times.7 Clearance
genotypes.4,76
rates range from 45 to 77%.7 Adverse events include local
discomfort, pruritus, irritation, burning, pain, xerosis, erythema,
Prognosis erosion, ulceration, and postinflammatory pigmentary changes
at the site of application.7,14 To minimize local adverse events,
If left untreated, penile warts may resolve spontaneously, stay
podophyllotoxin should be washed off 1–4 hours after
the same, or increase in size and number.3 Approximately one-
application.79 Sexual intercourse should be avoided when
third of penile warts regress without treatment and the average
podophyllotoxin is still on the skin.79
duration prior to resolution is approximately 9 months.4,77
Proper treatment has a clearance rate of 35–100% in 3–16 Imiquimod is available as 3.75 and 5% cream. Imiquimod
weeks.65 In spite of resolution of visible warts, HPV infection enhances the host’s innate and cellular immune response and
may persist and may result in recurrence of penile warts.4 combats HPV infection by binding to the dermal dendritic cells
The recurrence rate ranges from 25 to 67% within 6 months and macrophages through toll-like receptor-7.9 This results
of treatment.7,78 Patients with subclinical infection, recurrent in the production and release of proinflammatory cytokines,
infection from sexual contact, and immunodeficiency have such as interferon alpha (IFN-α), tumor necrosis factor alpha
higher recurrence rate.79 (TNF-α), and interleukin (IL)-1, IL-6, IL-8, and IL-12.7,79 The
secreted cytokines stimulate local immune effects that are
cytotoxic against HPV. Imiquimod also acts on cell-mediated
Management immunity by activating Langerhans cells, thereby increasing
Active treatment of penile warts is preferable to watchful the presentation of antigens for the T cells. Studies have shown
observation to speed up clearance of the lesions, assuage fears that topical application of 5% imiquimod cream is beneficial in
of transmission and autoinoculation, allay emotional stress, the treatment of penile warts.83 The 5% imiquimod is applied
improve cosmetic appearance, reduce social stigma associated three times per week till total clearance of the lesion or for a

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maximum of 16 weeks, while the 3.75% imiquimod is applied The success rate is about 75%.79 Adverse effects include
nightly for up to 8 weeks.9,79 Clearance rates are similar to those pain during treatment, erythema, peeling, vesicle, erosion,
of podofilox.7 Adverse events with topical imiquimod include ulceration, and dyspigmentation at the application site.82 A
local irritation, pruritus, burning, erythema, vesicles, erosions, recent phase II parallel-randomized study on 16 Iranian men
ulceration, and hypopigmentation at the application site and, with genital warts showed that cryotherapy using Wartner
less frequently, flu-like symptoms.14,79 To minimize local adverse compound that contains a mixture of 75% of dimethyl ether
events, the treatment area should be washed with soap and and 25% of propane is also effective. Further studies need
water 6–10 hours after application. to be done to confirm or refute this finding.86 Suffice to say,
cryotherapy using Wartner compound is less effective than
Sinecatechins ointment is a water extract of leaves of green tea
cryotherapy using liquid nitrogen.86
(Camellia sinensis) and available as 10 and 15% formulations.
It is believed that the medication works by decreasing viral Bichloroacetic and trichloroacetic acid can be used for the
replication through upregulation of apoptosis-associated genes treatment of small penile warts, as their ability to penetrate
and modulation of genes involved in the proinflammatory skin is limited.79 Either medication works by protein
response to HPV infection.7,79 Sinecatechins ointment is a safe coagulation with resultant cell destruction and eradication
and effective treatment of penile warts in immunocompetent of the penile wart.7 A burning sensation may be experienced
males aged 18 years and older.13,84 It is recommended that at the application site. Recurrences following the application
sinecatechins ointment be applied three times a day for up to of bichloroacetic or trichloroacetic acid are common. The
16 weeks.6,7 It is not necessary to wash the ointment off prior medication can be applied up to three times weekly.7 Clearance
to the next application.6 Two randomized, double-blind, phase rates range from 64 to 88%.7
III trials (n=1005) showed rates of complete clearance and
Oral cimetidine, a H2-receptor antagonist, presumably works
recurrence after 12 weeks of genital warts were significantly
by enhancing cell-mediated immunity against HPV.87 The
superior to the control group (p<0.001 and p<0.001,
recommended dose is 25–40 mg/kg/day. The medication is
respectively).6 Adverse effects include pruritus, burning,
safe, painless, and well tolerated.88
discomfort, irritation, pain, erythema, edema, induration,
vesicular rash, erosion, and ulceration at the application site, Electrocautery, pulsed dye laser therapy, carbon dioxide
which occur in approximately 20% of patients.6,7,13 Staining laser therapy, or surgical excision works by mechanical
of underwear is another nuisance aspect. A single-blind, destruction of the penile wart, and they may be required if
randomized controlled trial (n=42) showed that cryotherapy the lesion is extensive, bulky, or recalcitrant to conservative
plus sinecatechins 15% ointment was more effective in the treatment.14,79,89,90 These modalities of treatment have the
treatment of external genital warts compared to cryotherapy highest success rate but also have the potential of leaving
alone (−5.0 lesions versus −2.1 lesions, respectively, p=0.07).85 scars on the skin. Topical anesthesia, such as with Nanorap (a
hydrogel with 2.5% lidocaine and 2.5% prilocaine with 50%
of active products in nanocapsules) applied over the lesions
Clinician-administered therapies without occlusion 20 minutes before the procedure or a
Clinician-administered therapies include podophyllin, eutectic mixture of local anesthetics (EMLA) applied over the
cryotherapy with liquid nitrogen, bichloroacetic or lesions with occlusion for an hour before the procedure, should
trichloroacetic acid, oral cimetidine, surgical excision, be considered to reduce the discomfort/pain, which can be
electrocautery, and carbon dioxide laser therapy.80,81 disturbing for some individuals.44 General anesthesia may be
Podophyllin 25% liquid, derived from podophyllotoxin, necessary for surgical removal of large and extensive lesions.
works by arresting mitosis and causing tissue necrosis.7 The
medication is applied directly to the penile wart once a week
for up to 6 weeks, with a maximum of 0.5 ml per treatment.7
Alternate therapies
Podophyllin 25% liquid should be washed off 1–4 hours post- Patients who do not respond to first-line treatments may
treatment and should not be applied to any raw area.7 The respond to other therapies or a combination of treatment
clearance rate is approximately 62%.7 Because of the reported modalities.75,79 Second-line therapies include topical/
toxicity including death associated with its use, podofilox, its intralesional/intravenous cidofovir, topical 5-fluorouracil,
purified form, is preferred, which has a much better safety and topical ingenol mebutate.
profile.7
Antiviral therapy with topical, intralesional, or intravenous
Liquid nitrogen, a treatment of choice for penile warts, can be cidofovir may be considered for immunocompromised
applied via a spray gun or a cotton-tip applicator directly to patients with severe, refractory lesions.14 Cidofovir is an acyclic
and 2 mm surrounding the lesion.79 Liquid nitrogen works by nucleoside phosphonate that competitively inhibits viral
causing tissue damage and cell death through rapid freezing DNA polymerase, thereby preventing viral replication.79,91
with formation of ice crystals.79,86 The minimum temperature Adverse effects of topical or intralesional cidofovir include
required for destruction of the warts is −50°C, although some irritation, erosion, post-inflammatory pigmentary changes, and
authors believe that a temperature of −20°C is also effective.86 superficial scars at the site of application.88 The main adverse

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effect of intravenous cidofovir is nephrotoxicity, which can be in the target age.99–102 Vaccination is also recommended for
prevented by saline hydration and probenecid.91 men who are homosexual or immunocompromised through
age 26 years if not vaccinated before.100,101 HPV vaccination
Topical 5-fluorouracil has been shown to be effective in the
reduces the chance of HPV infection and subsequent penile
treatment of penile warts.92 5-fluorouracil is an antimetabolite
warts as well as penile cancers. Vaccinating both males and
fluoropyrimidine analog of the nucleoside pyrimidine. The
females is more beneficial in reducing penile warts than by
medication works by blocking the action of thymidylate
vaccinating only males, as males may acquire HPV infection
synthase and thereby stopping the production of DNA. A
from their female sexual partners. The prevalence of anogenital
Cochrane database systematic review of six randomized,
warts decreased significantly from 2008 to 2014, thanks to the
placebo-controlled trials involving 988 patients with genital
administration of the HPV vaccine.103 The annual percentage
warts showed that topical 5-fluorouracil was more effective
change among males aged 20–24 years was −6% (p=0.005).103
than no treatment or placebo (relative risk: 0.39; 95%
The decreased prevalence likely results from herd protection
confidence interval: 0.23–0.67).92 The authors cautioned
from vaccination among females. A 2017 systematic review
that further studies are necessary due to lack of high-quality
and meta-analysis of six studies (n=27,078) showed that HPV
randomized, placebo-controlled trials.92 Adverse events of
quadrivalent vaccine is efficacious in preventing anogenital
topical 5-fluorouracil include pain, burning, inflammation, and
warts in both males and females.104 The 9-valent vaccine
ulceration at the application site.79
(Gardasil-9) which has replaced the 4-valent vaccine (Gardasil)
Preliminary studies showed that topical application of targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and
ingenol mebutate gel is efficacious in the treatment of contains those virus-like particles.96,101,105 As such, the 9-valent
genital warts.93–95 Ingenol mebutate works by induction of vaccine is effective in the prevention of penile warts.105 The
cell death in proliferating keratinocytes and by stimulation bivalent vaccine (Cervarix) targets only HPV types 16 and 18
of an inflammatory response characterized by infiltration and is not effective in the prevention of penile warts.97 Safety
of neutrophils.95 Local skin irritation may occur after 24–48 data for the HPV vaccines are reassuring.102
hours.94,95 The recurrence rate is unknown.

Prevention Conclusion
Genital warts can be prevented, to a certain extent, by delaying
Penile warts are sexually transmitted disease caused by
sexual initiation and limiting the number of sexual partners.3
HPV. The condition can have negative psychosocial effects
Latex condoms, when used consistently and properly, reduce
on the patient and may adversely affect quality of life.
HPV transmission. Sexual partners with anogenital warts should
Although approximately one-third of penile warts regress
be treated.
without treatment, active treatment is preferred to speed up
HPV vaccines prior to the onset of sexual activity are effective clearance of the lesions, assuage fears of transmission and
in the primary prevention of HPV infection.5 This is because autoinoculation, allay emotional stress, improve cosmetic
the vaccines do not provide protection against diseases appearance, reduce social stigma associated with penile
from vaccine HPV types that the individual has acquired lesions, and alleviate symptoms. Active treatments may be
through prior sexual activity.96 The Advisory Committee on mechanical, chemical, immunomodulatory, and antiviral, and
Immunization Practices of the Centers for Disease Control often a combination of these. Thus far, no single treatment has
and Prevention, the American Academy of Pediatrics, the been shown to be consistently superior to other treatment
American College of Obstetricians and Gynecologists, the modalities. The choice of the treatment method should depend
American Academy of Family Practice, and the International on the physician’s comfort level with the various treatment
Papillomavirus Society recommend routine vaccination with options, the patient’s preference and tolerability of treatment,
HPV vaccine for girls and boys.81,97–101 The target age for and the number and severity of lesions. The comparative
vaccination is 11–12 years for girls and boys.100–102 The vaccine efficacy, ease of use, adverse effects, cost, and availability of the
can be administered as early as 9 years of age.97 Three doses treatment modality should also be taken into consideration.
of HPV vaccine should be given at 0, 1–2 (typically 2), and 6 HPV vaccines prior to the onset of sexual activity are effective
months.97 Catch-up vaccination is indicated for males through in the primary prevention of HPV infection. The target age for
age 21 years and females through age 26 years if not vaccinated vaccination is 11–12 years for both girls and boys.

Contributions: Professor Alexander KC Leung is the principal author. Dr Benjamin Barankin, Dr Kin Fon Leong, and Professor Kam Lun Hon are
the coauthors who contributed and helped with the drafting of this manuscript. All named authors meet the International Committee of Medical
Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their
approval for this version to be published.
Disclosure and potential conflicts of interest: The authors declare that there is no conflict of interest in preparing this article. The
International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at
http://www.drugsincontext.com/wp-content/uploads/2018/11/dic.212563-COI.pdf

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Acknowledgments: The photo images were taken by the authors with verbal consent of the respective patient. The patients are
unidentifiable and the photo images have not been previously published.
Funding declaration: There was no funding associated with the preparation of this article.
Copyright: Copyright © 2018 Leung AKC, Barankin B, Leong KF, Hon KL. Published by Drugs in Context under Creative Commons License Deed
CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified
below. No commercial use without permission.
Correct attribution: Copyright © 2018 Leung AKC, Barankin B, Leong KF, Hon KL. https://doi.org/10.7573/dic.212563. Published by Drugs in
Context under Creative Commons License Deed CC BY NC ND 4.0.
Article URL: https://www.drugsincontext.com/penile-warts-an-update-on-their-evaluation-and-management
Correspondence: Alexander KC Leung, The University of Calgary, Alberta Children’s Hospital, #200, 233 – 16th Avenue NW, Calgary, Alberta,
Canada T2M 0H5. aleung@ucalgary.ca
Provenance: invited; externally peer reviewed.
Submitted: 21 September 2018; Peer review comments to author: 16 November 2018; Revised manuscript received: 17 November 2018;
Accepted: 22 November 2018; Publication date: 19 December 2018.
Drugs in Context is published by BioExcel Publishing Ltd. Registered office: Plaza Building, Lee High Road, London, England, SE13 5PT.
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References
1. Costa-Silva M, Fernandes I, Rodrigues AG, Lisboa C. Anogenital warts in pediatric population. An Bras Dermatol. 2017;92(5):675–
681. http://dx.doi.org/10.1590/abd1806-4841.201756411
2. Leung AK, Kellner JD, Davies D. Genital infection with human papillomavirus in adolescents. Adv Ther. 2005;22(3):187–197.
http://dx.doi.org/10.1007/bf02849928
3. Leung AK, Barankin B. Genital warts. Consultant360.com. http://www.consultant360.com/articles/genital-warts. Accessed
September 1, 2018.
4. Scheinfeld N. Condylomata acuminata (anogenital warts) in adults: epidemiology, pathogenesis, clinical features, and diagnosis.
In: Post TW, ed. UpToDate. Waltham, MA. Accessed September 1, 2018.
5. Richards S. An overview of genital warts. Nurs Stand. 2014;28(24):46–50. http://dx.doi.org/10.7748/ns2014.02.28.24.46.e8344
6. Gupta AK, Daigle D. Sinecatechins 10% ointment: a green tea extract for the treatment of external genital warts. Skin Therapy
Lett. 2015;20(1):6–8. PubMed PMID: 25807215
7. Karnes JB, Usatine RP. Management of external genital warts. Am Fam Physician. 2014;90(5):312–318. PubMed PMID: 25251091
8. Leslie SW, Shenot PJ. Wart, Genital. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2018 Jan–2018 Mar 15.
9. Yuan J, Ni G, Wang T, et al. Genital warts treatment: beyond imiquimod. Hum Vaccin Immunother. 2018;14(7):1815–1819.
http://dx.doi.org/10.1080/21645515.2018.1445947
10. Patel H, Wagner M, Singhal P, Kothari S. Systematic review of the incidence and prevalence of genital warts. BMC Infect Dis.
2013;13:39. http://dx.doi.org/10.1186/1471-2334-13-39
11. Palefsky JM. Human papillomavirus infections: epidemiology and disease associations. In: Post TW, ed. UpToDate. Waltham, MA.
Accessed September 5, 2018.
12. Steben M, Garland SM. Genital warts. Best Pract Res Clin Obstet Gynaecol. 2014;28(7):1063–1073.
http://dx.doi.org/10.1016/j.bpobgyn.2014.07.002
13. Goldenberg G, Taylor M, Berman B, Kaufmann M, Abramovits W, Zeichner J. Sinecatechins ointment, 15% for the treatment of
external genital and perianal warts: proceedings of an expert panel roundtable meeting. J Clin Aesthet Dermatol. 2016;
9(3 Suppl 1):S2–S15. PubMed PMID: 29844847
14. Benjamin LT. Condylomata acuminata (anogenital warts) in children. In: Post TW, ed. UpToDate. Waltham, MA. Accessed
August 25, 2018.
15. Stefanaki C, Barakas G, Valari M, et al. Condylomata acuminata in children. Pediatr Infect Dis J. 2012;31(4):422–424.
http://dx.doi.org/10.1097/inf.0b013e318245a589
16. Dunne EF, Burstein GR, Stone KM. Anogenital human papillomavirus infection in males. Adolesc Med. 2003;14:613–632.
PubMed PMID: 15122164

Leung AKC, Barankin B, Leong KF, Hon KL. Drugs in Context 2018; 7: 212563. DOI: 10.7573/dic.212563 10 of 14
ISSN: 1740-4398
REVIEW – Penile warts drugsincontext.com

17. Sehgal VN, Koranne RV, Srivastava SB. Genital warts: current status. Int J Dermatol. 1989;28(2):75–85.
http://dx.doi.org/10.1111/j.1365-4362.1989.tb01322.x
18. Albero G, Castellsagué X, Giuliano AR, Bosch FX. Male circumcision and genital human papillomavirus: a systematic review and
meta-analysis. Sex Transm Dis. 2012;39(2):104–113. http://dx.doi.org/10.1097/olq.0b013e3182387abd
19. Firnhaber C, Sello M, Maskew M, et al. Human papillomavirus types in HIV seropositive men with penile warts in Johannesburg,
South Africa. Int J STD AIDS. 2011;22(2):107–109. http://dx.doi.org/10.1258/ijsa.2010.010306
20. Kaderli R, Schnüriger B, Brügger LE. The impact of smoking on HPV infection and the development of anogenital warts. Int J
Colorectal Dis. 2014;29(8):899–908. http://dx.doi.org/10.1007/s00384-014-1922-y
21. Zetola N, Klausner JD. Male circumcision reduces human papillomavirus incidence and prevalence: clarifying the evidence. Sex
Transm Dis. 2012;39(2):114–115. http://dx.doi.org/10.1097/olq.0b013e318242b4f3
22. Shimizu A, Hattori M, Kaira K, Ishikawa O. Keratotic condyloma acuminatum. J Dermatol. 2016;43(6):716–717.
http://dx.doi.org/10.1111/1346-8138.13266
23. Lopaschuk CC. New approach to managing genital warts. Can Fam Physician. 2013;59(7):731–736. PubMed PMID: 23851535
24. Veasey JV, Framil VM, Nadal SR, et al. Genital warts: comparing clinical findings to dermatoscopic aspects, in vivo reflectance confocal
features and histopathologic exam. An Bras Dermatol. 2014;89(1):137–140. http://dx.doi.org/10.1590/abd1806-4841.20141917
25. Campos MA, Sousa A, Lage G, et al. Blue-gray plaque of the penis. JAAD Case Rep. 2018;4(6):531–533.
http://dx.doi.org/10.1016/j.jdcr.2017.07.026
26. Dong H, Shu D, Campbell TM, Frühauf J, Soyer HP, Hofmann-Wellenhof R. Dermatoscopy of genital warts. J Am Acad Dermatol.
2011;64(5):859–864. http://dx.doi.org/10.1016/j.jaad.2010.03.028
27. Leung AK, Barankin B. Pearly penile papules. J Pediatr. 2014;165(2):409. http://dx.doi.org/10.1016/j.jpeds.2014.03.019
28. Leung AK, Barankin B. Fordyce spots. Consultant. 2016;56:377–378. https://www.consultant360.com/articles/fordyce-spots
29. Radhakrishnan S, Agarwal DC. Fordyce spots masquerading as penile warts. Med J Armed Forces India. 2016;72(4):384–385.
http://dx.doi.org/10.1016/j.mjafi.2015.12.008
30. Rane V, Read T. Penile appearance, lumps and bumps. Aust Fam Physician. 2013;42(5):270–274.
31. Bahce ZS, Akbulut S, Sogutcu N, Oztas T. Giant acrochordon arising from the thigh. J Coll Physicians Surg Pak. 2015;
25(11):839–840.
32. Ma H, Xia Y, Yin S, Lai W. Giant skin tag on the labium majorum. Int J Womens Dermatol. 2015;1(4):175–176.
http://dx.doi.org/10.1016/j.ijwd.2015.09.003
33. Lipoff JB, Chatterjee K. Acrochordon. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2018 Jan–2018 Jul 5.
34. Bartels A, Crandall M, Spring L. Recalcitrant genital papules. J Fam Pract. 2017;66(7):457–460. PubMed PMID: 28700763
35. Leung AKC, Leong KF, Lam JM. A case of congenital syphilis presenting with unusual skin eruptions. Case Rep Pediatr. 2018 Mar
25;2018:1761454. http://dx.doi.org/10.1155/2018/1761454
36. Bruins FG, van Deudekom FJ, de Vries HJ. Syphilitic condylomata lata mimicking anogenital warts. BMJ. 2015 Mar 17;350:h1259.
http://dx.doi.org/10.1136/bmj.h1259
37. Leung AK, Kong AY. Discrete papules on the thigh of a child. Molluscum contagiosum. Am Fam Physician. 2010;81(4):511.
PubMed PMID: 20148507
38. Leung AK. The natural history of molluscum contagiosum in children. Lancet Infect Dis. 2015;15(2):136–137.
http://dx.doi.org/10.1016/s1473-3099(14)71061-8
39. Leung AKC, Barankin B, Hon KLE. Molluscum contagiosum: an update. Recent Pat Inflamm Allergy Drug Discov. 2017;11(1):22–31.
http://dx.doi.org/10.2174/1872213x11666170518114456
40. Leung AK, Barankin B. An annular lesion on the elbow. Am Fam Physician. 2016;93(5):397–398. PubMed PMID: 26926977
41. Fathi K, Harangi F, Kravjak A, Pinter A. Subcutaneous granuloma annulare of the penis associated with a urethral anomaly: case
report and review of the literature. Pediatr Dermatol. 2014;31(4):e100–e103. http://dx.doi.org/10.1111/pde.12322
42. Mercieca L, Carabot P, Boffa MJ. Penile granuloma annulare. Skinmed. 2016;14(3):233–236. PubMed PMID: 27502267
43. Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186(18):E688. http://dx.doi.org/10.1503/cmaj.140434
44. Leung AK, Ng J. Generalized lichen nitidus in identical twins. Case Rep Dermatol Med. 2012;2012:982084.
http://dx.doi.org/10.1155/2012/982084
45. Lee WJ, Park OJ, Won CH, et al. Penile lichen nitidus successfully treated with topical pimecrolimus 1% cream. J Dermatol.
2013;40(6):499–500. http://dx.doi.org/10.1111/1346-8138.12089
46. Leung AK, Barankin B. Lichen planus. Consultant. 2014;54:137–138. https://www.consultant360.com/articles/lichen-planus
47. Badri T, Kenani N, Benmously R, Debbiche A, Mokhtar I, Fenniche S. Isolated genital annular lichen planus. Acta Dermatovenerol
Alp Pannonica Adriat. 2011;20(1):31–33. PubMed PMID: 21879203
48. Leung AK, Leung AA. Seborrheic keratosis. Consultant. 2012;52:573–575.
49. Part M, Svecová D, Brezová D, Breza J. Giant seborrheic keratoses on penis. J Sex Med. 2014;11(12):3119–3122.
http://dx.doi.org/10.1111/jsm.12676

Leung AKC, Barankin B, Leong KF, Hon KL. Drugs in Context 2018; 7: 212563. DOI: 10.7573/dic.212563 11 of 14
ISSN: 1740-4398
REVIEW – Penile warts drugsincontext.com

50. Adikari S, Philippidou M, Samuel M. A rare case of acquired lymphangioma circumscriptum of the penis. Int J STD AIDS.
2017;28(2):205–207. http://dx.doi.org/10.1177/0956462416657238
51. Zaballos P, Del Pozo LJ, Argenziano G, et al. Dermoscopy of lymphangioma circumscriptum: a morphological study of 45 cases.
Australas J Dermatol. 2018;59(3):e189–e193. http://dx.doi.org/10.1111/ajd.12668
52. Ayhan E. Lymphangioma circumscriptum: good clinical response to isotretinoin therapy. Pediatr Dermatol. 2016;33(3):e208–209.
http://dx.doi.org/10.1111/pde.12839
53. Stoner BP, Cohen SE. Lymphogranuloma venereum 2015: clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2015;61
Suppl 8:S865–873. http://dx.doi.org/10.1093/cid/civ756
54. Leung AK, Barankin B, Hon KL. Scabies. Consult Pediatr. 2016;15:613–616.
https://www.consultant360.com/articles/scabies-extremely-pruritic-rash-nighttime-intensity
55. Dhossche JM, Brodell RT, Al Hmada Y, Ward KH. Skin-colored papules of the penis. Pediatr Dermatol. 2015;32(1):145–146.
http://dx.doi.org/10.1111/pde.12403
56. Cardoso TA, dos Santos KR, Franzotti AM, Avelar JC, Tebcherani AJ, Pegas JR. Traumatic neuroma of the penis after circumcision –
case report. An Bras Dermatol. 2015;90(3):397–399. http://dx.doi.org/10.1590/abd1806-4841.20153233
57. Hoverson KR, Sasaki GT, Wohltmann WE. Traumatic neuroma of the penis. Dermatol Online J. 2014;20(1):21252.
PubMed PMID: 24456955.
58. Park HJ, Kim TN, Baek SR, Lee KM, Choi KU, Park NC. Penile traumatic neuroma: a late complication of penile
dorsal neurotomy to treat premature ejaculation. Sex Med. 2016;4(3):e221–224.
http://dx.doi.org/10.1016/j.esxm.2016.04.003
59. Salcedo E, Soldano AC, Chen L, et al. Traumatic neuromas of the penis: a clinical, histopathological and immunohistochemical
study of 17 cases. J Cutan Pathol. 2009;36(2):229–233. http://dx.doi.org/10.1111/j.1600-0560.2008.01014.x
60. Han H, Lei HE, Tian L, Zhang XD. Isolated penis schwannoma: a rare case report. Urol Case Rep. 2018;21:12–13.
http://dx.doi.org/10.1016/j.eucr.2018.07.017
61. Nguyen AH, Smith ML, Maranda EL, Punnen S. Clinical features and treatment of penile schwannoma: a systematic review. Clin
Genitourin Cancer. 2016;14(3):198–202. http://dx.doi.org/10.1016/j.clgc.2015.12.018
62. Marcucci C, Sabban EC, Friedman P, Peralta R, Calb I, Cabo H. Dermoscopic findings in bowenoid papulosis: report of two cases.
Dermatol Pract Concept. 2014;4(4):61–63. http://dx.doi.org/10.5826/dpc.0404a11
63. Deem S, Keane T, Bhavsar R, El-Zawahary A, Savage S. Contemporary diagnosis and management of squamous cell carcinoma
(SCC) of the penis. BJU Int. 2011;108(9):1378–1392. http://dx.doi.org/10.1111/j.1464-410x.2011.10647.x
64. Thapa S, Ghosh A, Shrestha S, Ghartimagar D, Narasimhan R, Talwar OP. Warty carcinoma penis: an uncommon variant. Case Rep
Pathol. 2017;2017:2937592. http://dx.doi.org/10.1155/2017/2937592
65. Lacey CY, Woodhall SC, Wikstrom A, et al. 2012 European guideline for the management of anogenital warts. J Eur Acad Dermatol
Venereol. 2013;27(3):e263–e270. http://dx.doi.org/10.1111/j.1468-3083.2012.04493.x
66. Steben M, LaBelle D. Genital warts: Canadians’ perception, health-related behaviors, and treatment preferences. J Low Genit Tract
Dis. 2012;16(4):409–415. http://dx.doi.org/10.1097/lgt.0b013e3182466ee3
67. Jeynes C, Chung MC, Challenor R. ‘Shame on you’ – the psychosocial impact of genital warts. Int J STD AIDS. 2009;20(8):557–560.
http://dx.doi.org/10.1258/ijsa.2008.008412
68. Kucukunal A, Altunay IK, Mercan S. Sexual dysfunction in men suffering from genital warts. J Sex Med. 2013;10:1585–1591.
http://dx.doi.org/10.1111/jsm.12132
69. Mortensen GL, Larsen HK. The quality of life of patients with genital warts: a qualitative study. BMC Public Health. 2010 Mar
7;10:113. http://dx.doi.org/10.1186/1471-2458-10-113
70. Paradisi A, Capizzi R, Ricci F, et al. Quality of life in patients with anogenital warts. Eur J Dermatol. 2013;23(6):837–842.
http://dx.doi.org/10.1684/ejd.2013.2171
71. Tan LS, Chio MT, Sen P, et al. Assessment of psychosocial impact of genital warts among patients in Singapore. Sex Health.
2014;11(4):313–318. http://dx.doi.org/10.1071/sh13189
72. Vriend HJ, Nieuwkerk PT, van der Sande MA. Impact of genital warts on emotional and sexual well-being differs by gender. Int J
STD AIDS. 2014;25(13):949–955. http://dx.doi.org/10.1177/0956462414526706
73. Cervigni M, Scotto V, Panei M, et al. Acute urethral obstruction due to condylomata acuminata. Obstet Gynecol. 1991;78:970–972.
PubMed PMID: 1923242.
74. Gormley RH, Kovarik CL. Human papillomavirus-related genital disease in the immunocompromised host: part I. J Am Acad
Dermatol. 2012;66(6):867.e1–14; quiz 881–2. http://dx.doi.org/10.1016/j.jaad.2010.12.050
75. Gormley RH, Kovarik CL. Human papillomavirus-related genital disease in the immunocompromised host: part II. J Am Acad
Dermatol. 2012;66(6):883.e1–17. http://dx.doi.org/10.1016/j.jaad.2010.12.049
76. Blomberg M, Friis S, Munk C, et al. Genital warts and risk of cancers: a Danish study of nearly 50000 patients with genital warts. J
Infect Dis. 2012;205(10):1544–1553. http://dx.doi.org/10.1093/infdis/jis228

Leung AKC, Barankin B, Leong KF, Hon KL. Drugs in Context 2018; 7: 212563. DOI: 10.7573/dic.212563 12 of 14
ISSN: 1740-4398
REVIEW – Penile warts drugsincontext.com

77. Allen AL, Siegfried EC. The natural history of condyloma in children. J Am Acad Dermatol. 1988;39(6):951–955.
http://dx.doi.org/10.1016/s0190-9622(98)70268-3
78. Jablonska S. Traditional therapies for the treatment of condylomata acuminata (genital warts). Australas J Dermatol.
1998;39(Suppl 1):S2–S4. PubMed PMID: 9842092
79. Scheinfeld N. Condylomata acuminata (anogenital warts): management of external condylomata acuminata in men. In: Post TW,
ed. UpToDate. Waltham, MA. Accessed September 5, 2018.
80. Yanofsky VR, Patel RV, Goldenberg G. Genital warts: a comprehensive review. J Clin Aesthet Dermatol. 2012;5(6):25–36. PubMed
PMID: 22768354
81. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015.
MMWR Recomm Rep. 2015;64(RR-03):1–37. PubMed PMID: 26042815
82. Recanati MA, Kramer KJ, Maggio JJ, Chao CR. Cantharidin is superior to trichloroacetic acid for the treatment of non-mucosal
genital warts: a pilot randomized controlled trial. Clin Exp Obstet Gynecol. 2018;45(3):383–386.
http://dx.doi.org/10.12891/ceog4112.2018
83. Rosen T, Nelson A, Ault K. Imiquimod cream 2.5% and 3.75% applied once daily to treat external genital warts in men. Cutis.
2015;96(4):277–282. PubMed PMID: 26682290
84. Stockfleth E, Meyer T. The use of sinecatechins (polyphenon E) ointment for treatment of external genital warts. Expert Opin Biol
Ther. 2012;12(6):783–793. http://dx.doi.org/10.1517/14712598.2012.676036
85. On SC, Linkner RV, Haddican M, et al. A single-blinded randomized controlled study to assess the efficacy of twice daily
application of sinecatechins 15% ointment when used sequentially with cryotherapy in the treatment of external genital warts.
J Drugs Dermatol. 2014;13(11):1400–1405. PubMed PMID: 25607709
86. Firooz A, Hosseini H, Izadi Firouzabadi L, Nassiri Kashani M, Nasrollahi SA. The efficacy and safety of other cryotherapy
compounds for the treatment of genital warts: a randomized controlled trial. J Dermatolog Treat. 2018;27:1–3.
http://dx.doi.org/10.1080/09546634.2018.1480745
87. Franco I. Oral cimetidine for the management of genital and perigenital warts in children. J Urol. 2000;164(3 Pt 2):1074–1075.
http://dx.doi.org/10.1097/00005392-200009020-00038
88. Leung AKC, Barankin B, Hon KLE. Molluscum contagiosum: an update. Recent Pat Inflamm Allergy Drug Discov. 2017;11(1):22–31.
http://dx.doi.org/10.2174/1872213x11666170518114456
89. Azizjalali M, Ghaffarpour G, Mousavifard B. CO(2) Laser therapy versus cryotherapy in treatment of genital warts; a Randomized
Controlled Trial (RCT). Iran J Microbiol. 2012;4(4):187–190. PubMed PMID: 23205250
90. Veitch D, Kravvas G, Al-Niaimi F. Pulsed dye laser therapy in the treatment of warts: a review of the literature. Dermatol Surg.
2017;43(4):485–493. http://dx.doi.org/10.1097/dss.0000000000001023
91. Blaizot R, Dutkiewicz AS, Guillet S, Pham-Ledard A, Beylot-Barry M. Intravenous cidofovir for diffuse genital warts
in the setting of multifactorial immunosuppression. J Eur Acad Dermatol Venereol. 2017;31(3):e162–e163.
http://dx.doi.org/10.1111/jdv.13880
92. Batista CS, Atallah AN, Saconato H, da Silva EM. 5-FU for genital warts in non-immunocompromised individuals. Cochrane
Database Syst Rev. 2010 Apr 14;(4):CD006562. http://dx.doi.org/10.1002/14651858.cd006562.pub2
93. Braun SA, Gerber PA. Ingenol mebutate for the management of genital warts in sensitive anatomic locations. J Am Acad
Dermatol. 2017;77(1):e9–e10. http://dx.doi.org/10.1016/j.jaad.2017.01.034
94. Dika E, Vaccari S, Fanti PA, Patrizi A. Ingenol mebutate: an unconventional treatment proposal. Dermatol Ther. 2016;29(1):72.
http://dx.doi.org/10.1111/dth.12265
95. Schopf RE. Ingenol mebutate gel is effective against anogenital warts – a case series in 17 patients. J Eur Acad Dermatol Venereol.
2016;30(6):1041–1043. http://dx.doi.org/10.1111/jdv.13097
96. Foerster V, Khangura S, Severn M. HPV vaccination in men: a review of clinical effectiveness, cost-effectiveness, and guidelines
[Internet]. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2017 Mar 24. PubMed PMID: 29266907
97. Cox JT. Human papillomavirus vaccinations. In: Post TW, ed. UpToDate. Waltham, MA. Accessed September 15, 2018.
98. Markowitz LE, Dunne EF, Saraiya M, et al. Human papillomavirus vaccination: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-05):1–30. PubMed PMID: 25167164
99. [No authors listed]. Committee opinion no 641: human papillomavirus vaccination. Obstet Gynecol. 2015;126(3):e38–e43.
http://dx.doi.org/10.1097/aog.0000000000001052
100. Park IU, Introcaso C, Dunne EF. Human papillomavirus and genital warts: a review of the evidence for the 2015 Centers for
Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Clin Infect Dis. 2015;61 Suppl 8:S849–855.
http://dx.doi.org/10.1093/cid/civ813
101. Petrosky E, Bocchini JA Jr, Hariri S, et al; plus Centers for Disease Control and Prevention (CDC). Use of 9-valent human
papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization
practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300–304. PubMed PMID: 25811679

Leung AKC, Barankin B, Leong KF, Hon KL. Drugs in Context 2018; 7: 212563. DOI: 10.7573/dic.212563 13 of 14
ISSN: 1740-4398
REVIEW – Penile warts drugsincontext.com

102. [No authors listed]. Committee Opinion No. 704 Summary: human papillomavirus vaccination. Obstet Gynecol. 2017;129(6):1155–
1156. http://dx.doi.org/10.1097/aog.0000000000002111
103. Flagg EW, Torrone EA. Declines in anogenital warts among age groups most likely to be impacted by human papillomavirus
vaccination, United States, 2006–2014. Am J Public Health. 2018;108(1):112–119. http://dx.doi.org/10.2105/ajph.2017.304119
104. Tejada RA, Vargas KG, Benites-Zapata V, Mezones-Holguín E, Bolaños-Díaz R, Hernandez AV. Human papillomavirus vaccine
efficacy in the prevention of anogenital warts: systematic review and meta-analysis. Salud Publica Mex. 2017;59(1):84–94.
http://dx.doi.org/10.21149/7824
105. Pitisuttithum P, Velicer C, Luxembourg A. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Expert
Rev Vaccines. 2015;14(11):1405–1419. http://dx.doi.org/10.1586/14760584.2015.1089174

Leung AKC, Barankin B, Leong KF, Hon KL. Drugs in Context 2018; 7: 212563. DOI: 10.7573/dic.212563 14 of 14
ISSN: 1740-4398