Genital Warts 

Updated: Oct 16, 2018
Author: Delaram Ghadishah, MD; Chief Editor: William D James, MD 

Overview

Background

Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). More than 100 types of double-stranded HPV papovaviruses have been isolated thus far, and, of these, about 35 types have affinity to genital sites. Many have been linked directly to an increased neoplastic risk in men and women.

Two general categories of genital human papillomavirus (HPV) exist: low-risk benign HPV lesions and high-risk neoplastic HPV lesions. The low-risk strains are responsible for genital warts and recurrent respiratory papillomatosis (RRP), as well as low-grade cervical lesions. Two types, 6 and 11, account for more than 90% of genital warts and most cases of RRP. These are least likely to have malignant potential.

Thirteen human papillomavirus (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; more than 70% of cervical, vaginal, and penile cancers are caused from 2 types. 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.

Also see Human Papillomavirus.

Pathophysiology

Human papillomavirus (HPV) invades cells of the basal layer of the epidermis, penetrating skin and mucosal microabrasions in the genital area.

A latency period of 3 weeks to 9 months 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. However, most infections are transient and clear up within 2 years without intervention.

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.

Etiology

Genital warts are caused by several of the epidermotropic human papillomaviruses (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.

Epidemiology

Frequency

United States

Annual incidence is 1%, and genital warts are considered the most common sexually transmitted disease (STD). A four-fold or more increase in prevalence has been reported in the last two decades; prevalence reportedly exceeds 50%. The lifetime risk of infection is 50% in sexually active individuals.

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.

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.

Prognosis

Many cases of genital warts fail to respond to treatment or recur after adequate response. The 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

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.

There is an associated psychosocial burden of external lesions on the genitalia.

Patient Education

Identify and educate persons at risk. For patient education resources, visit the Sexual Health Center. Also, see the patient education article Genital Warts.

 

Presentation

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 one area is more common.

History may indicate previous or other current sexually transmitted diseases (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 Examination

Single or multiple papular eruptions may be seen. Eruptions can be pearly, filiform, fungating, cauliflower (shown in the image below), or plaquelike.

Genital warts. "Cauliflower" condyloma of the peni Genital warts. "Cauliflower" condyloma of the penis. Courtesy of Tsu-Yi Chuang, MD, MPH.

Lesions can be quite smooth (particularly on the penile shaft), verrucous, or lobulated. Some appear harmless, as in the image below; others have a more disturbing appearance. Multiple sites often are involved simultaneously.

Genital wart in pubic area. Genital wart in pubic area.

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, as shown in the images below.

Genital warts. Small papilloma on the shaft of pen Genital warts. Small papilloma on the shaft of penis. Courtesy of Tsu-Yi Chuang, MD, MPH.
Genital warts. Small papilloma of the vulva. Court Genital warts. Small papilloma of the vulva. Courtesy of Tsu-Yi Chuang, MD, MPH.

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.

Complications

Possible complications are as follows:

  • Local disfigurement

  • Transformation to genitourinary malignancies in both males and females

  • Transmission to neonate or partners

  • Recurrence: According to Diamantis et al, recurrence rates for anogenital warts ranged from 19% at 3 months to 23% at 6 months.[1]

 

DDx

Differential Diagnoses

 

Workup

Approach Considerations

As indicated by history and physical examination, consider testing for other STDs (eg, HIV, gonorrhea, chlamydia, syphilis).

The following are 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

Also see the laboratory testing article Genital Human Papillomavirus.

 

Treatment

Approach Considerations

Symptomatic treatment may be warranted in emergency situations. Use pressure to stop bleeding, if present. Relieve urethral obstruction (rare). Search for evidence of coexistent STDs; treat them if found and indicated. Further treatment, screening, and vaccination guidelines from the American College of Obstetricians and Gynecologists and Centers for Disease Control and Prevention are available.[2, 3, 4]  Also see Human Papillomavirus.

Untreated

If visible genital warts are left untreated, they can undergo spontaneous resolution, increase in size, increase in number, or remain unchanged. Complete resolution of lesions after 2 years occurs in 75% of individuals without intervention.

Ablative therapy

Cryotherapy[3] can be used. 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, clearance occurs about 75% of the time 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) and curettage have been used.

Surgical excision[3] has the highest success rate and lowest recurrence rate. Initial cure rates are 63-91%.

Carbon dioxide laser treatment is used for extensive or recurrent genital warts. The procedure requires local, regional, or general anesthesia. (A eutectic mixture of local anesthetics [EMLA] cream may be used as an alternative anesthetic.) Clearance rates are more than 90%, but reoccurrence can be up to 40%. HPV-6 DNA has been detected in the carbon dioxide laser plume; therefore, the laser operator is at risk of developing mucosal warts.

With infrared coagulation, a beam of infrared light is delivered to the affected lesions, causing tissue coagulation and necrosis. Treatment is successful in about 80% of cases.

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).

Vaccination[5, 6]

The 9-valent HPV vaccine (Gardasil 9 [9vHPV]) is available in the United States to decrease the risk of certain cancers and precancerous lesions in males and females. The 9vHPV vaccine covers HPV subtypes 6, 11, 16, 18, 31, 33, 45, 52, and 58. Cervarix (2vHPV) and Gardasil (4vHPV) were discontinued in the United States in October 2016. Children and adolescents aged 15 years and younger need two, not three, doses of the 9vHPV vaccine; this Advisory Committee on Immunization Practices (ACIP) recommendation stems from the vaccine’s enhanced immunogenicity in preteens and adolescents aged 9-14 years. The schedule for older adolescents and young adults aged 15-45 years is three inoculations within 6 months.

Approval for adults up to age 45 years was based on a study of approximately 3200 women aged 27-45 years followed for an average of 3.5 years. The 9vHPV vaccine was 88% effective in preventing the combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine.[7, 8]

The effectiveness of 9vHPV in men aged 27-45 years is inferred from the data described above in women, as well as from efficacy data in younger men (aged 16-26 y) and immunogenicity data from a clinical trial in which 150 men, aged 27-45 years, received a three-dose regimen over 6 months.[8]

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. The 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.

Consultations

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

Prevention

The 9-valent HPV vaccine (Gardasil 9 [9vHPV]) is available in the United States to decrease the risk of certain cancers and precancerous lesions in males and females. 9vHPV vaccine covers HPV subtypes 6, 11, 16, 18, 31, 33, 45, 52, and 58. Cervarix (2vHPV) and Gardasil (4vHPV) were discontinued in the United States in October 2016. Children and adolescents aged 15 years and younger need two, not three, doses of the 9vHPV vaccine; this ACIP recommendation stems from the vaccine’s enhanced immunogenicity in preteens and adolescents aged 9-14 years. The schedule for older adolescents and young adults aged 15 through 45 years is three inoculations within 6 months.

Approval for adults up to 45 years old was based on a study of approximately 3200 women aged between 27 through 45 years followed for an average of 3.5 years. 9vHPV vaccine was 88% effective in preventing the combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine.[7, 8]

Effectiveness of 9vHPV in men aged 27 through 45 years is inferred from the data described above in women, as well as efficacy data in younger men (aged 16 through 26 years) and immunogenicity data from a clinical trial in which 150 men, aged 27 through 45 years, received a 3-dose regimen over 6 months.[8]

Long-Term Monitoring

Ensure follow-up with a dermatologist, OB/GYN (females), or urologist (males) within 1 week. Perform a workup for human papillomavirus (HPV) and other sexually transmitted diseases (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.

 

Medication

Medication Summary

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.

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 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. Diamantis et al note that complete clearance of warts occurred in 50% of patients treated with imiquimod 5% cream (administered once-daily, 3 times/wk, up to 16 wk).[1]

Keratolytics

Class Summary

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

Podophyllum resin (Podocon-25, Podo-Ben-25, Podofin)

Podophyllum resin is a powdered mixture of resins removed from the May apple (mandrake) (Podophyllum peltatum linne). It is 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 sources. A cure rate of 20-50% can be expected if used as a single agent. Clearance rates are much higher if cryotherapy is used simultaneously.

Podofilox (Condylox)

Podofilox is a 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. The 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.

Trichloroacetic acid topical (Tri-Chlor)

Trichloroacetic acid topical cauterizes skin, keratin, and other tissues. Although caustic, it causes less local irritation and systemic toxicity than other agents in the same class. However, the response is often incomplete and recurrences are frequent.

5-Fluorouracil (Efudex, Fluoroplex)

5-Fluorouracil has antimetabolic, antineoplastic, and immunostimulative activity. It is useful to prevent recurrence in patients who are immunocompromised if started within 4 weeks of condyloma ablation. Mild local discomfort can be treated with cortisol cream.

Miscellaneous topical ointment

Class Summary

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

Kunecatechins (Veregen)

Kunecatechins is a botanical drug product for topical use consisting of extract from green tea leaves. Its mode of action is unknown, but it does elicit antioxidant activity in vitro. It is indicated for topical treatment of external genital and perianal warts (condylomata acuminatum) in immunocompetent patients.

Interferons

Class Summary

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.

Interferon alfa-n3 (Alferon N)

Interferon alfa-n3 is 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.

The recurrence rate is 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.

Immune response modifiers

Class Summary

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.

Imiquimod (Aldara) 5% cream

Imiquimod induces secretion of interferon alpha and other cytokines; the mechanisms of action are unknown.

Vaccines

Class Summary

The 9-valent HPV vaccine is indicated for prevention of HPV-associated dysplasias and neoplasia, including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions.

Children and adolescents aged 15 years and younger need two, not three, doses of the HPV vaccine; this ACIP recommendation stems from the vaccine’s enhanced immunogenicity in preteens and adolescents aged 9-14 years. The schedule for older adolescents and adults aged 15-45 years is three inoculations within 6 months.

Human papillomavirus vaccine, nonavalent (Gardasil 9)

This vaccine induces a humoral immune response to 9 HPV subtypes: 6, 11, 16, 18, 31, 33, 45, 52, and 58. It is indicated in males and females aged 9-45 years to prevent HPV-associated diseases.