Background: Genital warts are an epidermal manifestation attributed to
the epidermotropic human papillomavirus (HPV). Over 75 types of
double-stranded HPV papovavirus have been isolated thus far. Many have
been linked directly to an increased neoplastic risk in men and women.
Approximately 90% of all genital warts are related to HPV types 6 and
11 (HPV-6, HPV-11). These are the least likely to have neoplastic
potential.
Thirteen HPV types (ie, 33, 35, 39, 40, 43, 45, 51-56, 58) have a
moderate risk for neoplastic conversion; HPV-16 and HPV-18 are
considered high risk. This picture is complicated by the proven
coexistence of many types in the same patient (10-15%), lack of
adequate information on the oncogenic potential of many other types,
and ongoing identification of additional HPV-related clinical
pathology. For example, bowenoid papulosis, seborrheic keratoses, and
Buschke-Lowenstein tumorspreviously parts of the differential
diagnosis of genital wartsall have been linked to HPV infections.
* Bowenoid papulosis consists of rough papular eruptions and is
considered a carcinoma in situ. Eruptions can be red, brown, or flesh
colored and may regress or become invasive.
* Seborrheic keratoses previously were considered a benign skin
manifestation. These consist of rough plaques and have an infectious
and an oncogenic potential.
* Buschke-Lowenstein tumor (giant condyloma) is a fungating,
locally invasive, low-grade cancer attributed to HPV.
Pathophysiology: HPV invades cells of the basal layer of the
epidermis, penetrating skin and mucosal microabrasions in the genital
area.
A latency period of months to years may ensue. Following that period,
viral DNA, capsids, and particles are produced. Host cells become
infected and develop the morphologic atypical koilocytosis of genital
warts.
Most frequently affected are the penis, vulva, vagina, cervix,
perineum, and perianal area. These mucosal lesions occasionally can be
found in the oropharynx, larynx, and trachea. HPV-6 even has been
reported in other uncommon areas (eg, extremities).
Multiple simultaneous lesions are common and may involve subclinical
states as well as different anatomic sites. Subclinical infections
have an infectious and oncogenic potential.
Consider the possibility of sexual abuse in pediatric cases; however,
remember that infection by direct manual contact or, rarely, by
indirect transmission from fomites may occur. Additionally, passage
through an infected vaginal canal at birth may cause respiratory
lesions in infants.
Frequency:
* In the US: Annual incidence is 1%, and genital warts are
considered the most common sexually transmitted disease (STD). A
4-fold or more increase in prevalence has been reported in the last 2
decades; prevalence reportedly exceeds 50%.
* Internationally: Reports vary on international prevalence, but
available data from England, Panama, Italy, the Netherlands, and other
developed and underdeveloped countries show HPV infections to be at
least as common internationally as in the United States.
Mortality/Morbidity: Mortality is secondary to malignant
transformation to a carcinoma. This oncogenic potential, which is rare
with HPV-6 and HPV-11 (the most commonly isolated viruses), reportedly
triples the risk of genitourinary cancer among infected males.
* HPV infection appears to be more common and worse in patients
with various types of immunologic deficiencies. Recurrence rate, size,
discomfort, and risk of oncologic progression are highest among these
patients. Secondary infection is uncommon. Latent illness often
becomes active during pregnancy.
* Vulvar warts may interfere with parturition. Trauma then may
occur, producing crusting or erythema. Acute urethral obstruction may
occur in women.
* Bleeding has been reported due to flat warts of the penile
urethral meatus (usually associated with HPV-16) and in the large
lesions that can occur during pregnancy. Lesions may lead to
disfigurement.
Sex: Both sexes are susceptible to infection. Overt disease may be
more common in men (reported in 75% of cases); however, infection may
be more prevalent in women.
Age: Prevalence is greatest in those persons aged 17-33 years, with a
peak incidence in persons aged 20-24 years.
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History:
* Painless bumps, pruritus, and discharge are the chief complaints
encountered with genital warts.
* Generally, two thirds of individuals who have sexual contact
with a partner who has genital warts develop lesions within 3 months.
* A history involving multiple lesions, rather than a single
isolated wart, is more common.
* Involvement of more than 1 area is more common.
* History may indicate previous or other current STDs.
o Oral, laryngeal, or tracheal mucosal lesions (uncommon)
presumably transfer through oral-genital contact.
o History of anal intercourse warrants a thorough search for
perianal lesions.
* Urethral bleeding or urinary obstruction (uncommon) may be the
presenting complaint when the wart involves the meatus.
* Vaginal bleeding during pregnancy may be due to condyloma
eruptions. Coital bleeding also may occur.
* Latent illness may become active, particularly with pregnancy
and immunosuppression.
* Lesions may regress spontaneously, remain static, or progress.
Physical:
* Single or multiple papular eruptions may be seen.
o Eruptions can be pearly, filiform, fungating, cauliflower,
or plaquelike.
o Lesions can be quite smooth (particularly on the penile
shaft), verrucous, or lobulated.
o Some appear harmless; others have a more disturbing
appearance.
o Multiple sites often are involved simultaneously.
* Color may vary from that of the skin to erythema or
hyperpigmentation.
* Check for irregularities in shape, form, or color that may
suggest melanoma or malignancy.
* Seek perianal lesions, particularly in patients with a history
or risk of immunosuppression or anal intercourse.
* Search for evidence of other STDs (eg, ulcerations, adenopathy,
vesicles, discharge).
* Genital warts have a propensity for the penile glans and shaft
in men and for the vulvovaginal and cervical areas in women.
* Urethral meatus and mucosal lesions can occur.
* Some lesions are subclinical, and some are hidden by hair or in
the inner aspect of uncircumcised foreskin.
* Although earlier reports have suggested otherwise, the presence
of external genital warts warrants a thorough search for cervical and
urethral lesions.
o Such internal lesions have been found in more than half of
females with external lesions.
o Infected males have a 20% chance or more (in one report)
of having subclinical urethral lesions.
o More than 50% of female patients with external lesions
have negative Papanicolaou test (Pap smear) results but positive HPV
infection results using in situ hybridization.
* Pruritus may be a complaint.
* Discharge may be evident.
Causes:
* Genital warts are caused by several of the epidermotropic HPVs.
o HPV-6 and HPV-11 most commonly are isolated; however, many
of the more than 60 types of HPV may cause condyloma.
o Male sex partners of women with cervical intraepithelial
neoplasia often have infections of the same viral type.
* Smoking, oral contraceptives, multiple sex partners, and early
coital age are risk factors for acquiring genital wart
ther Tests:
* As indicated by history and physical examination, consider
testing for other STDs (eg, HIV, gonorrhea, chlamydia, syphilis).
* The following are not ED tests. These are listed strictly for
educational purposes and to assist in the understanding and management
of potential complications.
o Pap smear - Used to look for papillomatosis, acanthosis,
koilocytic abnormality, and mild nuclear abnormality
o Colposcopy (stereoscopic microscopy) - Used to look for
papillomatosis, acanthosis, koilocytic abnormality, and mild nuclear
abnormality
o Biopsy - Indicated for lesions that are atypical,
recurrent after initial success, or resistant to treatment and in
patients with a high risk for neoplasia or immunosuppression
o Filter hybridization (Southern blot and slot-blot
hybridization), in situ hybridization, and polymerase chain reaction -
Used for diagnosis and typing of HPV
o Hybrid capture
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Emergency Department Care:
* Although an in-depth discussion of the treatment of genital
warts (ie, type of workup, treatment regimens, necessary follow-up) is
beyond the scope of ED practice, symptomatic treatment may be warranted.
o Use pressure to stop bleeding, if present.
o Relieve urethral obstruction (rare).
o Search for evidence of coexistent STDs; treat them if
found and indicated.
* The following measures are beyond the scope of the ED and are
presented for educational purposes only.
o Cryotherapy
+ Use an open spray or cotton-tipped applicator for
10-15 seconds, and repeat as needed. Lift away mobile skin from the
underlying normal tissue before freezing.
+ This is an excellent first-line treatment,
particularly for perianal lesions.
+ Response rates are high with few adverse sequelae.
+ Adverse reactions include pain during treatment,
erosion, ulceration, and postinflammatory hypopigmentation of skin.
+ Cryotherapy is safe for use during pregnancy.
o Electrodesiccation (smoke plume may be infective)
o Curettage
o Surgical excision
+ Excision has the highest success rate and lowest
recurrence rate.
+ Initial cure rates are 63-91%.
o Carbon dioxide laser treatment
+ This treatment is used for extensive or recurrent
genital warts.
+ HPV-6 DNA has been detected in the carbon dioxide
laser plume; therefore, treatment is potentially infectious.
+ The procedure requires local, regional, or general
anesthesia. (A eutectic mixture of local anesthetics [EMLA] cream may
be used as an alternative anesthetic.)
Consultations:
* No emergent consultation is indicated.
* Outpatient follow-up with an obstetrician, gynecologist, or
urologist is indicated.
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Do not administer the following medications in the ED. These agents
are listed strictly for educational purposes and to help readers
understand and manage potential complications.
Warts generally regress spontaneously within months or years. Remove
genital or laryngeal warts, however, because of the possibility of
malignant transformation.
The Centers for Disease Control and Prevention (CDC) recommends
keratolytic agents and antimitotic agents as alternative regimens to
cryotherapy to treat external genital/perianal warts, vaginal warts,
and urethral meatus warts.
Drug Category: Keratolytics -- Cause the cornified epithelium to
swell, soften, macerate, and then desquamate.
Drug Name
Podophyllum resin (Podocon-25, Podo-Ben-25, Podofin) -- Powdered
mixture of resins removed from the May apple (mandrake) (Podophyllum
peltatum linne). Cytotoxic agent used topically to treat genital
warts. Arrests mitosis in metaphase, an effect it shares with other
cytotoxic agents (eg, vinca alkaloids). Podophyllotoxin is the active
agent, and its strength varies with the type of podophyllum resin
used. American podophyllum contains a fourth the amount of Indian
source. A cure rate of 20-50% can be expected if used as a single agent.
Adult Dose Sparingly apply 10-25% concentration onto lesions 1-2
times/wk; use 1 gtt at a time, allowing drying between gtt until area
is covered
Treat only intact lesions; wash treatment area 1-2 h after first
application; in subsequent treatments, patient can wait 4-6 h before
washing off agent
Pediatric Dose Apply as in adults
Contraindications Documented hypersensitivity; diabetes; impaired
peripheral circulation; avoid use on mucous membranes, eyes, bleeding
warts, moles, birthmarks, or unusual warts with hair
Interactions None reported
Pregnancy X - Contraindicated in pregnancy
Precautions Powerful caustic and severe irritant; do not use if
surrounding tissue is swollen or irritated; do not apply 25% solution
near mucous membranes; do not use large amounts; avoid contact with cornea
Drug Name
Podofilox (Condylox) -- Topical antimitotic that can be chemically
synthesized or purified from plant families Coniferae and
Berberidaceae (eg, species of Juniperus and Podophyllum). Treatment of
anogenital warts results in necrosis of visible wart tissue. Exact
mechanism of action is unknown. Genital warts are epidemiologically
associated with cervical carcinoma. Slightly higher cure rates can be
expected with podofilox than with podophyllin. Additionally, this
agent is useful for prophylaxis.
Adult Dose 0.5% solution applied bid for 3 d and discontinued for 4 d;
repeat this on-and-off cycle for up to 4 wk
Use no more than 0.5 mL of solution or 0.5 g of gel qd; treat <10 cm2
of tissue qd
Thoroughly wash hands after each application
Pediatric Dose Not established
Contraindications Documented hypersensitivity
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Avoid contact with eyes; if eye contact, immediately flush
eye with copious quantities of water and seek medical advice; not for
use on mucous membranes of genital area, including urethra, rectum,
and vagina; do not exceed frequency of application or duration of
usage; not recommended by itself for recurrent warts or perianal or
genital mucous membranes (distinguishing between these conditions can
be difficult); obtain histopathologic confirmation if the diagnosis is
doubtful
Drug Name
Trichloroacetic (Tri-Clor), Dichloroacetic (Bichloracetic) acids --
Cauterizes skin, keratin, and other tissues. Although caustic, causes
less local irritation and systemic toxicity than other agents in the
same class. However, response is often incomplete and recurrences are
frequent.
Adult Dose Paint onto lesions, avoiding uninvolved skin; can be used
in anal areas; repeat q1-2wk; 3-4 treatments may be necessary
Treated area requires no cleansing after several hours
Pediatric Dose Not established
Contraindications Documented hypersensitivity; not for use on
premalignant or malignant lesions
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions External use only; restrict use to treatment areas only;
if acid spilled on normal tissue or if too much applied, remove
immediately and wash with water; sodium bicarbonate may be applied as
a local antidote
Drug Name
5-Fluorouracil (Efudex, Fluoroplex) -- Has antimetabolic,
antineoplastic, and immunostimulative activity. Useful to prevent
recurrence in patients who are immunocompromised if started within 4
wk of condyloma ablation.
Mild local discomfort can be treated with cortisol cream.
Adult Dose 5% cream qd or periodically for 10 wk
1% cream bid for 2-6 wk
Pediatric Dose Not established
Contraindications Documented hypersensitivity; pregnancy
Interactions None reported
Pregnancy X - Contraindicated in pregnancy
Precautions Incidence of inflammatory reactions may occur with
occlusive dressings; porous gauze dressing may be applied for cosmetic
reasons without increase in reaction; avoid prolonged exposure to
sunlight or UV radiation; increased absorption may occur through
ulcerated or swollen skin; use care near eyes, nose, and mouth; wash
hands immediately after application; prolonged use may result in
erosive dermatitis and mucositis; additionally, there is a risk of
developing vaginal adenosis and clear cell adenocarcinoma with this
treatment; pain, pruritus, burning, irritation, inflammation, allergic
contact dermatitis, and telangiectasia are possible adverse effects
Drug Category: Interferons -- Naturally produced protein with
antiviral, antitumor, and immunomodulatory actions. Alpha-, beta-, and
gamma-interferons exist and may be administered topically,
systemically, and intralesionally.
Drug Name
Interferon Alfa-n3 (Alferon N) -- Approved by the FDA for injection
in refractory condyloma acuminata. The mechanism by which interferons
exert antitumor activity is poorly understood. Direct
antiproliferative action against tumor cells and modulation of the
host immune response may play important roles.
Recurrence rate of 20-40%, but the recurrence rate after successful
treatment is lower than with other treatment modalities. Nevertheless,
intralesional interferon is expensive and requires repeated office visits.
Adult Dose 250,000 U intralesionally twice weekly for a maximum of 8
wk; not to exceed 2.5 million U per treatment session
Pediatric Dose Not established
Contraindications Documented hypersensitivity to mouse immunoglobulin,
egg protein, or neomycin
Interactions Potential risk of renal failure when administered
concurrently with interleukin-2; theophylline may increase toxicity by
reducing clearance; cimetidine may increase antitumor effects;
zidovudine and vinblastine may increase toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Numerous adverse reactions may occur with IM
administration, including myalgias, fever and chills, GI symptoms,
transient leukopenia, thrombocytopenia, LFT abnormalities, and serum
lipid abnormalities, as well as a theoretical risk of viral
transmission with natural interferon products; viral symptoms abate
with time, and all adverse effects resolve once therapy is stopped;
viral symptoms can be treated with acetaminophen or NSAIDs in the
interim; monitor periodically to determine if the patient is
responding to treatment; if patient does not respond within 6 mo,
discontinue treatment; if a response to treatment is seen, continue
treatment until either no further improvement is observed or the
laboratory parameters have been stable for about 3 mo (not known
whether continued treatment after that time is beneficial); caution in
debilitating cardiovascular disease, severe pulmonary disease,
diabetes mellitus with ketoacidosis, coagulation disorders, severe
myelosuppression, or seizure disorders
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Further Outpatient Care:
* Ensure follow-up with an obstetrician or gynecologist (females)
or with a urologist (males) within 1 week.
* Perform a workup for HPV and other STDs as indicated.
* Treat the patient using medications; if medications are
ineffective, treat with cryotherapy, curettage, electrodesiccation,
surgical excision, carbon dioxide laser treatment, or combination therapy.
* Evaluate and treat sexual partner(s).
* Search for immunosuppression in patients with treatment failures
and recurrences.
* Perform a tissue biopsy if recurrences or treatment failures occur.
In/Out Patient Meds:
* Podofilox (purified podophyllotoxin) is available for home use
by the patient.
o A 0.5% solution is applied twice daily for 3 consecutive
days for up to 4 weeks.
o Slightly higher cure rates are expected than with podophyllin.
o Podofilox is useful for prophylaxis.
o Podofilox is not recommended as the sole treatment for
recurrent warts.
Deterrence/Prevention:
* No treatment is 100% effective.
o Vaccines are unavailable.
o Sexual abstinence and monogamy are protective.
o Condoms may discourage transmission.
Complications:
* Local disfigurement
* Transformation to genitourinary malignancies in both males and
females
* Transmission to neonate or partners
* Recurrence
Prognosis:
* Many cases fail to respond to treatment or recur after adequate
response.
* Recurrence rate of cervical dysplasia in women is not altered by
treatment of their sex partners.
* Recurrence rates exceed 50% after 1 year and have been
attributed to the following:
o Recurrent infection from sexual contact
o Long incubation period of HPV
o Location of the virus in superficial skin layers away from
lymphatics
o Persistence of the virus in the surrounding skin, in the
hair follicle, or in sites inadequately reached by the intervention
o Missed or deep lesions
o Subclinical lesions
o Underlying immunosuppression
Patient Education:
* Identify and educate persons at risk.
* For excellent patient education resources, visit eMedicine's
Sexually Transmitted Diseases Center. Also, see eMedicine's patient
education article Genital Warts.
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Medical/Legal Pitfalls:
* Failure to inform patients of potential risk of malignant
transformation of lesions
* Failure to indicate necessity for follow-up, even after
treatment eradicates lesions
* Failure to recognize the possibility of subclinical and
intravaginal or cervical lesions and failure to search for them
* Failure to indicate treatment availability and follow-up
* Failure to inform patients of the risk of HPV transmission to
sex partners and neonates
* Failure to inform patient of necessity to treat partners
* Failure to search for immunosuppression in patients with
treatment failures and recurrences
Special Concerns:
* Pregnancy
o Latent infections may become activated with numerous large
lesions.
o Lesions often present or increase during pregnancy.
o Lesions may make vaginal delivery difficult if they are in
the cervix, vagina, or vulva.
o Lesions tend to bleed easily.
o Lesions often regress spontaneously after delivery.
* Pediatrics
o Neonates may become infected during passage through an
infected birth canal.
o Incidence of perinatal transmission to the infant pharynx
may be as high as 50%; transmission occurs most frequently with HPV-6
and HPV-11.
o Incidence of genital infection in neonates is 4%, although
the American College of Obstetrics and Gynecology currently does not
recommend cesarean delivery due solely to positive HPV status.