CONDYLOMATA ACUMINATA

Morgan Ashleigh Smith, DO • Tayseer

Husain Chowdhry,
MD, MA • E. James Kruse, DO
BASICS
DESCRIPTION
• Condylomata acuminata are soft, skin-colored, fleshy
lesions (commonly
called genital warts) that are caused by human papillomavirus
(HPV):
– Warts appear singly or in groups (a single wart is a
“condyloma”; multiple
warts are “condylomas” or “condylomata”); small or large;
typically appear
on the anogenital skin (penis, scrotum, introitus, vulva,
perianal area); and
may occur in the anogenital tract (vagina, cervix, rectum,
urethra, anus);
also conjunctival, nasal, oral, and laryngeal warts
• System(s) affected: skin/exocrine, reproductive,
occasionally respiratory
• HIV considerations:
– Treatment of external genital warts should not be different
for HIV-infected
persons (1).
– Lesions may be larger or more numerous (1)
– May not respond as well to therapy as
immunocompetent persons (1)
Pediatric Considerations
• Consider sexual abuse if seen in children, although
children can be infected by
other means (e.g., transfer from wart on another child’s
hand or prolonged
latency period) (2).
• American Academy of Pediatrics recommends all
school-aged children who
present with lesions be evaluated for abuse and screened
for other STDs (2).
Pregnancy Considerations
• Warts often grow larger during pregnancy and regress
spontaneously after
delivery.
• Virus does not cross the placenta. Treatment during
pregnancy is somewhat
controversial. Cesarean section is not absolutely indicated for
maternal
condylomata (3)[A].

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• Cervical infection has been found to be a risk
factor for preterm birth (3)[A].
• Few documented cases of laryngeal papillomas due to
HPV transmission at
the time of delivery. Although rare, the condition is
life-threatening (4).
• HPV vaccination is contraindicated in pregnancy.
• The safety of imiquimod, sinecatechins, podophyllin,
and podofilox during
pregnancy has not been established (3)[C].
EPIDEMIOLOGY
• HPV types 6 and 11 associated with 90% of
condylomata acuminata. Types
16, 18, 31, 33, and 35 may be found in warts and may be
associated with highgrade intraepithelial dysplasia in
immunocompromised states such as HIV.
• Highly contagious; incubation period may be from 1 to
8 months. Initial
infections may very well go unrecognized, so a “new”
outbreak may be a
relapse of an infection acquired years prior.
• Predominant age: 15 to 30 years
• Predominant sex: 1:1 male to female
• Most infections are transient and clear spontaneously
within 2 years.
Incidence
One study population demonstrated that from 2007 to
2010, with the
introduction of HPV vaccines, the incidence of genital warts
decreased 35%
(from 0.94% per year to 0.61% per year) in females <21
years, and decreased
19% in males <21.
Prevalence
• Most common viral sexually transmitted infection (STI)
in the United States.
Most sexually active men and women will have acquired a
genital HPV
infection, usually asymptomatic, at some time.
• Peak prevalence in ages 17 to 33 years
• 10–20% of sexually active women may be actively
infected with HPV. Studies
in men suggest a similar prevalence.
• Pregnancy and immunosuppression favor recurrence
and increased growth of
lesions.
ETIOLOGY AND PATHOPHYSIOLOGY
HPV is a circular, double-stranded DNA molecule. There are
>120 HPV

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subtypes. HPV types that cause genital warts do not cause
anogenital cancers.
RISK FACTORS
• Usually acquired by sexual activity
– Young adults and adolescents
– Multiple sexual partners; short interval between meeting
new sex partner
and first intercourse
– Not using protective barriers
– Young age of commencing sexual activity
– History of other STI
• Immunosuppression (particularly HIV)
GENERAL PREVENTION
• Sexual abstinence or monogamy
• Quadrivalent HPV vaccine available against genital
warts and cervical cancer.
This vaccine is targeted to adolescents before the period of
their greatest risk
for exposure to HPV. The vaccine does not treat previous
infections:
– Immunity has been documented to last at least 5
years after HPV
vaccination.
– The HPV quadrivalent vaccine (Gardasil) protects
against the two most
common HPV serotypes (types 6 and 11, which cause most
anogenital
warts) and the two most cancer-promoting types (16 and
18) (5).
– Quadrivalent vaccine is indicated for females and
males ages 9 to 26 years:
Vaccine is administered IM; 3 doses at 0, 2, and 6 months
to achieve
optimal seroconversion (6).
– Vaccine efficacy for preventing external genital warts is
related to age of
administration of 1st dose: 76% if aged <20 years, 93% if
<14 years.
• Bivalent HPV vaccine is available but does not cover
the HPV types that
cause most condyloma lesions (Cervarix) (5).
• Quadrivalent vaccine has been proven effective in
prevention of external
lesions in males 16 to 26 years of age (5).
• Use of condoms is partially effective, although warts
may be easily spread by
lesions not covered by a condom (e.g., 40% of infected
men have scrotal
warts).
• Abstinence until treatment completed

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COMMONLY ASSOCIATED CONDITIONS
• >90% of cervical cancer associated with HPV
types 16, 18, 31, 33, and 35
• 60% of oropharyngeal and anogenital squamous
cell carcinomas are
associated with HPV
• STIs (e.g., gonorrhea, syphilis, chlamydia), AIDS

DIAGNOSIS
HISTORY
• Explore sexual history, contraception use, and other
lifestyle topics.
• Most warts are asymptomatic but symptoms include
– Pruritus, burning, redness, pain, bleeding
– Vaginal discharge
– Large warts may cause obstructive symptoms in the
anus (with defecation)
or vaginal canal (with intercourse or childbirth)
PHYSICAL EXAM
• Lesions often have a typical rough, warty appearance
with multiple fingerlike
projections but may be soft, sessile, and smooth.
• Large lesions are cauliflower-like and may grow to
>10 cm.
• Most common sites: penis, vaginal introitus, and
perianal region
• May be seen anywhere on the anogenital epithelium
or in the anogenital tract
• Warts often occur in clusters.
• Bleeding or irritation of the lesions may be noted.
DIFFERENTIAL DIAGNOSIS
• Condylomata lata (flat warts of syphilis)
• Lichen planus
• Normal sebaceous glands
• Seborrheic keratosis
• Molluscum contagiosum
• Keratomas, micropapillomatosis
• Scabies
• Crohn disease
• Skin tags
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• Melanocytic nevi
• Vulvar intraepithelial neoplasia
• Squamous cell carcinoma
DIAGNOSTIC TESTS & INTERPRETATION
• Diagnosis is usually clinical, made by unaided visual
examination of the
lesions.
• Biopsy
• Acetowhitening test: Subclinical lesions can be
visualized by wrapping the
penis with gauze soaked with 5% acetic acid (vinegar) for 5
minutes. Using a
10× hand lens or colposcope, warts appear as tiny white
papules. A shiny
white appearance of the skin represents foci of epithelial
hyperplasia
(subclinical infection), but because of low specificity, the CDC
recommends
against routine use of this test to screen for HPV
mucosal infection.
Initial Tests (lab, imaging)
• Usually not required for diagnosis
• Serologic tests for syphilis may be helpful to rule out
condylomata lata.
• Other testing for STIs
• Pap smear may be indicated.
Follow-Up Tests & Special Considerations
Because squamous cell carcinoma may resemble or
coexist with condylomata,
biopsy may be considered for lesions refractory to therapy.
Diagnostic Procedures/Other
• Biopsy with highly specialized identification techniques,
such as HPV DNA
detected through polymerase chain reaction, is rarely useful.
• Colposcopy, antroscopy, anoscopy, and urethroscopy
may be required to
detect anogenital tract lesions.
• Screening men who have sex with men (MSM)
with anal Pap smears is
controversial.

TREATMENT
GENERAL MEASURES

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• May resolve spontaneously
• Change therapy if no improvement after 3 treatments,
not complete clearance
after 6 treatments, or therapy’s duration or dosage exceeds
manufacturer’s
recommendations.
• Appropriate screening/counseling of partners
MEDICATION
First Line
• No single therapy for genital warts is ideal for all patients
or clearly superior
to other therapies.
• Recommendations for external genital warts, patient-applied:
– Podofilox (Condylox): antimitotic action; apply 0.5%
solution or gel to
warts twice daily (allowing to dry) for 3 consecutive days at
home followed
by 4 days of no therapy; may repeat up to 4 total cycles;
maximum of 0.5
mL/day or area less than 10 cm
(3)[A],(7)
– Imiquimod (Aldara): immune enhancer; self-treatment
with a 5% cream
applied once daily at bedtime 3 times weekly until
warts resolve for up to
16 weeks. Wash off with soap and water 6 to 10 hours
after application.
Imiquimod has been noted to weaken condoms and
diaphragms; therefore,
patients should refrain from sexual contact while the cream is
on the skin
(3)[A],(8).
– Sinecatechins (Veregen): immune enhancer and
antioxidant, extract from
green tea; apply a 0.5-cm strand of ointment 3 times daily
for up to 16
weeks. Do not wash off after use (3)[A].
2
• Recommendations for external genitalwarts,
provider-applied:
– Cryotherapy: liquid nitrogen applied to warts for two
10-second bursts with
thawing in between; usually requires 2 to 3 weekly
sessions (3)[A]
– Podophyllin 10–25% in tincture of benzoin. Apply
directly to warts, air-dry
in office before coming into contact with clothes. Wash
off in 1 to 4 hours.
Repeat every 7 days in office until gone (3)[A],(7).
– Trichloroacetic acid (TCA): 80% solution. Apply only to
warts;
powder/talc to remove unreacted acid. Repeat in office at
weekly intervals;
ideal for isolated lesions in pregnancy (3)[A].
• Recommendations for exophytic cervical warts: biopsy to
exclude high-grade

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squamous intraepithelial lesion (SIL) (3)[A]
• Recommendations for vaginal warts: cryotherapy or TCA
or bichloracetic
acid (BCA) 80–90% (3)[A]
• Recommendations for urethral meatus warts: cryotherapy
or podophyllin 10–
25% in compound tincture of benzoin (3)[A]
• Recommendations for anal warts: cryotherapy, TCA or
BCA 80–90%, or
surgery; specialty consultation for intra-anal warts (3)[A]
Pregnancy Considerations
Cryotherapy, surgery, or TCA. Medications contraindicated in
pregnancy:
podophyllin, podophyllotoxin, sinecatechins, interferon, and
imiquimod (3)[C]
Second Line
Intralesional interferon, photodynamic therapy, topical cidofovir
(3)[A]
SURGERY/OTHER PROCEDURES
• Larger warts may require surgical excision, laser
treatment, or
electrocoagulation (including infrared therapy):
– Precaution: Laser treatment may create smoke plumes
that contain HPV.
CDC recommendation is for the use of a smoke evacuator no
less than 2
inches from the surgical site. Masks are recommended; N95
the most
efficacious (9)[A].
• Intraurethral, external (penile and perianal), anal, and
oral lesions can be
treated with fulgurating CO2 laser. Oral or external
penile/perianal lesions can
also be treated with electrocautery or surgery.

ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
No restrictions, except for sexual contact
Patient Monitoring
• Patients should be seen every 1 to 2 weeks until
lesions resolve.
• Patients should follow up 3 months after completion of
treatment.
• Persistent warts require biopsy.

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• Sexual partners require monitoring.
PATIENT EDUCATION
• Provide information on HPV, STI prevention, and
condom use.
• Explain to patients that it is difficult to know how
or when a person acquired
an HPV infection; a diagnosis in one partner does not
prove sexual infidelity
in the other partner.
• Emphasize the need for women to follow
recommendations for regular Pap
smears.
PROGNOSIS
• Asymptomatic infection persists indefinitely.
• Treatment has not clearly been shown to decrease
transmissible infectivity.
• Warts may clear with treatment or resolve
spontaneously. However,
recurrences are frequent, particularly in the first 3 months,
and may
necessitate repeated treatments.
COMPLICATIONS
• Cervical dysplasia (probably does not occur with type 6
or 11, which cause
most warts)
• Malignant change: Progression of condylomata to cancer
rarely, if ever,
occurs, although squamous cell carcinoma may coexist
in larger warts.
• Urethral, vaginal, or anal obstruction from treatment
• The prevalence of high-grade dysplasia and cancer
in anal canal is higher in
HIV-positive than in HIV-negative patients, probably because of
increased
HPV activity.

REFERENCES
1. Gormley RH, Kovarik CL. Human
papillomavirus-related genital disease in
the immunocompromised host: part II. J Am Acad
Dermatol.
2012;66(6):883.e1–883.e17; quiz 899–900.
2. Unger ER, Fajman NN, Maloney EM, et al.
Anogenital human
papillomavirus in sexually abused and nonabused children:
a multicenter
study. Pediatrics. 2011;128(3):e658–e665.
3. Workowski KA, Bolan GA; Centers for Disease
Control and Prevention.
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Sexually transmitted diseases treatment guidelines, 2015.
MMWR Recomm
Rep. 2015;64(RR-03):1–137.
4. Gerein V, Schmandt S, Babkina N, et al. Human
papilloma virus (HPV)associated gynecological alteration in
mothers of children with recurrent
respiratory papillomatosis during long-term observation. Cancer
Detect Prev.
2007;31(4):276–281.
5. Centers for Disease Control and Prevention. FDA
licensure of bivalent human
papillomavivaccine (HPV2, Cervarix) for use in females and
updated HPV
vaccination recommendations from the Advisory Committee
on
Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep
2010;59(20):626–629.
6. Centers for Disease Control and Prevention.
Recommendations on the use of
quadrivalent human papillomavirus vaccine in
males—Advisory Committee
on Immunization Practices (ACIP), 2011. MMWR Morb Mortal
Wkly Rep.
2011;60(50):1705–1708.
7. Stockfleth E, Beti H, Orasan R, et al. Topical
Polyphenon E in the treatment
of external genital and perianal warts: a randomized
controlled trial. Br J
Dermatol. 2008;158(6):1329–1338.
8. Gotovtseva EP, Kapadia AS, Smolensky MH, et
al. Optimal frequency of
imiquimod (aldara) 5% cream for the treatment of external
genital warts in
immunocompetent adults: a meta-analysis. Sex Transm Dis.
2008;35(4):346–
351.
9. NIOSH Health Hazard Evaluation and Technical
Assistance Reports, HETA
85-126-1932 (1988) and HETA 88-101-2008 (1990)

ADDITIONAL READING
• Bauer HM, Wright G, Chow J. Evidence of human
papillomavirus vaccine
effectiveness in reducing genital warts: an analysis of California
public family
planning administrative claims data, 2007–2010. Am J
Public Health.
2012;102(5):833–835.
• Giuliano AR, Palefsky JM, Goldstone S, et al.
Efficacy of quadrivalent HPV
vaccine against HPV infection and disease in males. N
Engl J Med.
2011;364(5):401–411.
• Gormley RH, Kovarik CL. Human
papillomavirus-related genital disease in
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the immunocompromised host: part I. J Am Acad
Dermatol.
2012;66(6):867.e1–867.e14; quiz 881–882.

CODES
ICD10
A63.0 Anogenital (venereal) warts

CLINICAL PEARLS
• Condylomata acuminata are soft, skin-colored, fleshy
lesions caused by HPV
subtypes 6, 11, 16, 18, 31, 33, and 35.
• Quadrivalent HPV vaccine addresses the two most
common HPV serotypes to
be contracted in warts types 6 and 11 and the two most
cancer-promoting
types 16 and 18 (Gardasil).
• Vaccine: 0.5 mL IM first dose and at months 2 and
6
• The majority of sexually active men and women
will have acquired a genital
HPV infection, usually asymptomatic, at some time.
• No single therapy for genital warts is ideal for all patients
or clearly superior
to other therapies.
• Quadrivalent HPV vaccine is effective in preventing
HPV infection,
particularly if administered prior to the onset of engaging in
sexual activity.
Gardasil is approved and recommended for use in males
and females aged 9 to
26 years