AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Introduction
• Clinical
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• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). More than 75 types of double-stranded HPV papovaviruses 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 tumors—previously parts of the differential diagnosis of genital warts—all 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

United States

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%.

International

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 persons aged 17-33 years, with a peak incidence in persons aged 20-24 years.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.
• • Oral, laryngeal, or tracheal mucosal lesions (uncommon) presumably transfer through oral-genital contact.
  • 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.
• • Eruptions can be pearly, filiform, fungating, cauliflower, or plaquelike.
  • Lesions can be quite smooth (particularly on the penile shaft), verrucous, or lobulated.
  • Some appear harmless; others have a more disturbing appearance.
  • 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.
• • Such internal lesions have been found in more than half of females with external lesions.
  • Infected males have a 20% chance or more (in one report) of having subclinical urethral lesions.
  • 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.
• • HPV-6 and HPV-11 most commonly are isolated; however, many of the more than 60 types of HPV may cause condyloma.
  • 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 warts.

DIFFERENTIALS

Section 4 of 11  

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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Darier disease
Hailey-Hailey disease
Neoplasia
Nevi
Pearly penile papules
Vulvar neurofibromatosis
Vulvar vestibular papillae

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
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• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Other 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.
• • Pap smear - Used to look for papillomatosis, acanthosis, koilocytic abnormality, and mild nuclear abnormality
  • Colposcopy (stereoscopic microscopy) - Used to look for papillomatosis, acanthosis, koilocytic abnormality, and mild nuclear abnormality
  • 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
  • Filter hybridization (Southern blot and slot-blot hybridization), in situ hybridization, and polymerase chain reaction - Used for diagnosis and typing of HPV
  • Hybrid capture

TREATMENT

Section 6 of 11  

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• Medication
• Follow-up
• Miscellaneous
• Multimedia
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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.
• • Use pressure to stop bleeding, if present.
  • Relieve urethral obstruction (rare).
  • 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.
• • Untreated: If visible genital warts are left untreated, they can undergo spontaneous resolution, increase in size, increase in number, or remain unchanged.
  • Ablative therapy
    • 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. 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.
    • Electrodesiccation (smoke plume may be infective)
    • Curettage
    • Surgical excision: Excision has the highest success rate and lowest recurrence rate. Initial cure rates are 63-91%.
    • 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.)
  • Immune-based therapy
    • Physician administered treatments include acid applications (bichloroacetic acid or trichloroacetic acid) and interferon injections with antiviral mechanisms.
    • Medications for home use include imiquimod 5% cream, podofilox gel or solution, and antiproliferative compounds (5-fluorouracil).
    • HPV vaccines: Two HPV vaccine candidates have proven to be highly effective in clinical trials: Gardasil and Cervarix. Gardasil, Merck's HPV vaccine, was licensed by the Food and Drug Administration (FDA) in June 2006 for the prevention of cervical cancers and other diseases caused by HPV in females. It is composed of a viruslike particle consisting of recombinant L1 proteins from HPV types 6, 11, 16, and 18. It has been recommended by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices to be routinely given to girls at age 11-12 years. It can be administered starting at age 9 years, with catch-up vaccinations recommended for females aged 13-26 years. The vaccine is not established as CDC policy until it is accepted by the director of the CDC. Cervarix is GlaxoSmithKline's HPV vaccine candidate and focuses on cancer prevention with L1 proteins from HPV types 16 and 18 only. This vaccine will likely be approved and licensed in late 2006.The vaccinesdonoteliminate the need for other prevention strategies and screening.

Consultations

• No emergent consultation is indicated.
• Outpatient follow-up with a dermatologist, an OB/GYN, or a urologist is indicated.

MEDICATION

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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 CDC recommends keratolytic agents, antimitotic agents, and immune-response modifiers as alternative regimens to cryotherapy to treat external genital/perianal warts, vaginal warts, and urethral meatus warts.

Drug Category: Keratolytics

These agents cause the cornified epithelium to swell, soften, macerate, and then desquamate.

Drug Name	Podofilox (Condylox)
Description	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
Description	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 on to 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)
Description	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: Miscellaneous topical ointment

Another topical product that has gained FDA approval for genital warts includes kunecatechins.

Drug Category: Interferons

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha-, beta-, and gamma-interferons exist and may be administered topically, systemically, and intralesionally.

Drug Category: Immune response modifiers

These agents are indicated for treatment of genital warts. Induces secretion of interferon alpha and other cytokines; mechanisms of action are unknown. They may be more effective in women than in men.

Drug Category: Vaccines

A HPV vaccine is now available for prevention of HPV-associated dysplasias and neoplasia including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions. The immunization series should be completed in girls and young women aged 9-26 years.

FOLLOW-UP

Section 8 of 11  

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Further Outpatient Care

• Ensure follow-up with a dermatologist, OB/GYN (females), or 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.
• • A 0.5% solution is applied twice daily for 3 consecutive days followed by 4 days of no therapy. The cycle can be repeated up to 4 times.
  • Slightly higher cure rates are expected than with podophyllin.
  • Podofilox is useful for prophylaxis.
  • Podofilox is not recommended as the sole treatment for recurrent warts.
• Imiquimod (Aldara) 5% cream: The cream is applied qhs, 3 times a week for a treatment period of 16 weeks. The treatment area should be washed with soap and water 6-10 hours after application.

Deterrence/Prevention

• No treatment is 100% effective.
• • The FDA has recently approved a vaccine for HPV.
  • Sexual abstinence and monogamy are protective.
  • 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:
• • Recurrent infection from sexual contact
  • Long incubation period of HPV
  • Location of the virus in superficial skin layers away from lymphatics
  • Persistence of the virus in the surrounding skin, in the hair follicle, or in sites inadequately reached by the intervention
  • Missed or deep lesions
  • Subclinical lesions
  • 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.

MISCELLANEOUS

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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
• • Latent infections may become activated with numerous large lesions.
  • Lesions often present or increase during pregnancy.
  • Lesions may make vaginal delivery difficult if they are in the cervix, vagina, or vulva.
  • Lesions tend to bleed easily.
  • Lesions often regress spontaneously after delivery.
• Pediatrics
• • Neonates may become infected during passage through an infected birth canal.
  • Incidence of perinatal transmission to the infant pharynx may be as high as 50%; transmission occurs most frequently with HPV-6 and HPV-11.
  • 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.

MULTIMEDIA

Section 10 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Genital wart in pubic area.
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Media file 2:  Genital wart in pubic area.
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Media file 3:  Genital wart in pubic area.
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Media file 4:  Genital wart in pubic area (close-up). Note the pearly appearance.
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Media file 5:  Warts, genital. Condyloma acuminatum. Courtesy of Tsu-Yi Chuang, MD, MPH.
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Media file 6:  Warts, genital. Small papilloma of the vulva. Courtesy of Tsu-Yi Chuang, MD, MPH.
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Media file 7:  Warts, genital. "Cauliflower" condyloma of the penis. Courtesy of Tsu-Yi Chuang, MD, MPH.
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Media file 8:  Warts, genital. Small papilloma on the shaft of penis. Courtesy of Tsu-Yi Chuang, MD, MPH.
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Media file 9:  Warts, genital. Small papilloma of the anus. Courtesy of Tsu-Yi Chuang, MD, MPH.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
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• Multimedia
• References

• American Academy of Dermatology. Genital Warts. 2006. Accessed June 6, 2006. 2006. [Full Text].
• Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines. 2002. Accessed June 6, 2006. [Full Text].
• Centers for Disease Control and Prevention. ACIP Provisional Recommendations for the Use of Quadrivalent HPV Vaccine. 2006. Accessed August 18, 2006. [Full Text].
• Chan PD, Winkle PJ, Winkle CR. Condyloma acuminata. Current Clinical Strategies - Family Medicine. 2nd ed. 1995: 209-10.
• Congilosi SM, Madoff RD. Current therapy for recurrent and extensive anal warts. Dis Colon Rectum. Oct 1995;38(10):1101-7. [Medline].
• Garrido JL. Human papilloma virus--H.P.V. condyloma. Current studies in diagnosis, treatment and prognosis. Clin Exp Obstet Gynecol. 1996;23(2):99-102. [Medline].
• Kresge KJ. Cervical cancer vaccines. Introduction of vaccines that prevent cervical cancer and genital warts may fore-shadow implementation and acceptability issues for a future AIDS vaccines. IAVI Rep. Nov-Dec 2005;9(5):1-5. [Medline].
• Mayeaux EJ, Harper MB, Barksdale W, Pope JB. Noncervical human papillomavirus genital infections. Am Fam Physician. Sep 15 1995;52(4):1137-46, 1149-50. [Medline].
• Prasad CJ. Pathobiology of human papillomavirus. Clin Lab Med. Sep 1995;15(3):685-704. [Medline].
• Rosen T. Sexually transmitted diseases 2006: a dermatologist's view. Cleve Clin J Med. Jun 2006;73(6):537-8, 542, 544-5 passim. [Medline].
• Sykes NL Jr. Condyloma acuminatum. Int J Dermatol. May 1995;34(5):297-302. [Medline].
• Vandepapeliere P, Barrasso R, Meijer CJ, et al. Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination. J Infect Dis. Dec 15 2005;192(12):2099-107. [Medline].

Article Last Updated: Jan 18, 2007