Anogenital warts

Anogenital warts are flat or pedunculated exophytic lesions on the anogenital mucosa or perineal skin caused by the human papillomavirus (HPV). Transmission is primarily sexual, but nonsexual transmission can occur. Lesions are often asymptomatic but can cause itching or pain. Diagnosis is clinical; biopsy may be considered in the case of diagnostic uncertainty. Treatment options include topical agents (e.g., imiquimod, podofilox), cryotherapy, surgical removal, and laser therapy, tailored to patient preference and the size and number of warts. HPV infection is difficult to eradicate; the risk of transmission and recurrence of warts persists even after treatment. HPV prevention with the HPV vaccine is the most effective preventive measure.

See also “HPV infection” and “Cutaneous warts.”

• Prevalence: 1% of the sexually active population ^[1]
• Prevalence is higher among immunocompromised individuals with HIV compared to the overall population. ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: HPV types that infect the mucosal epithelium (e.g., HPV types 6 and 11) ^[2][3][4]
• Routes of transmission ^[2]
  • Sexual ^[3]
  • Nonsexual (e.g., skin-to-skin contact)
• See also “Risk factors for HPV infection.”

HPV types 6 and 11 cause ∼ 90% of anogenital warts. ^[2][3][4]

• Flat, papular, or pedunculated exophytic, cauliflower-like lesions
• Located on any part of the anogenital mucosa (e.g., glans penis, vagina, cervix, anal canal) and/or perineal skin
• Typically asymptomatic; occasionally cause pruritus or pain

• Primarily clinical
  • Acetowhitening may aid visualization (nonspecific; not routinely recommended). ^[1][4]
  • Perform pelvic examination, digital rectal examination, and/or anoscopy as needed. ^[4]
• Indications for biopsy ^[1][4]
  • Diagnostic uncertainty
  • Immunocompromised state (e.g., due to HIV infection)
  • Atypical features
  • Lesions that worsen or do not improve with treatment
  • Exophyic cervical warts
• Refractory lesions: Consider syphilis testing to rule out condyloma lata. ^[4]

HPV testing is not recommended for genital warts, as results are nonspecific and do not alter management. ^[4]

• Other sexually transmitted genital lesions (e.g., condyloma lata)
• Skin tags
• Molluscum contagiosum
• Seborrheic keratosis
• Intraepithelial neoplasia (e.g., bowenoid papulosis)
• Malignancy

Bowenoid papulosis

Bowenoid papulosis is an HSIL that resembles squamous cell carcinoma in situ on histology. Compared to Bowen disease, it tends to occur in younger individuals and has a lower risk of malignant transformation. ^[5][6]

• Etiology: : most commonly HPV 16 ^[5][6][7]
• Epidemiology: most common in men 20–40 years of age ^[7][8]
• Clinical features: multiple flat, red-brown macules and papules typically located in the anogenital region ^[6]
• Diagnostics: : Diagnosis is based on clinical features and biopsy findings. ^[8][9]
  • Dermoscopy may aid visualization. ^[10]
  • Biopsy is recommended in all patients to rule out differential diagnosis (e.g., squamous cell carcinoma in situ). ^[8]
• Treatment ^[7][9]
  • Options are similar to those for treatment of anogenital warts, e.g.:
    • Topical therapy
    • Ablation
    • Excision
  • Reassess patients 3–6 months after treatment to evaluate for recurrence.
• Prognosis ^[7]
  • Spontaneous resolution is uncommon but can occur.
  • Recurrence is common.
  • Increased risk of penile SCC and cervical intraepithelial neoplasia ^[11]

Correlate biopsy findings with clinical features, as histopathology findings of Erythroplasia of Queyrat, Bowen disease, and Bowenoid papulosis can be difficult to distinguish from one another. ^[8]

Flat condylomata

Flat condylomata are also referred to as flat penile lesions in individuals with male genitalia, and LSIL of the vulva in individuals with female genitalia.

• Etiology: mucosal HPV types, including high-risk HPV ^[12]
• Clinical features ^[11]
  • Flat, white-brown, slightly elevated lesions in the anogenital region
  • May be asymptomatic or manifest with itching, burning, and/or dyspareunia
• Diagnostics
  • Diagnosis is clinical; acetowhitening may aid visualization of subclinical lesions. ^[12]
  • Consider biopsy in the case of diagnostic uncertainty; findings include low-grade intraepithelial lesions. ^[13][14]
• Management
  • Consider watchful waiting; most lesions regress within 1–2 years. ^[13][15]
  • Treatment of symptomatic patients is the same as treatment of anogenital warts. ^[11]

The differential diagnoses listed here are not exhaustive.

Determine management using shared decision-making, considering size and distribution warts, associated symptoms, and patient preferences. For management in children and in pregnant and immunocompromised individuals, see “Special patient groups.”

General principles ^[4]

• Treatment options include topical and procedural therapies.
• Consider watchful waiting based on patient preference.
• Offer STI testing to detect concomitant infections.
• Advise patients to notify current sexual partners of diagnosis.
• Counsel patients that:
  • Recurrence of anogenital warts is common.
  • Female individuals with genital warts do not require more frequent screening for cervical cancer. ^[4]
  • Condom use may prevent transmission of genital warts.
• Follow up at 3 months to evaluate treatment response.

HPV infection is difficult to eradicate. After treatment for anogenital warts, there is still a risk of transmission to sexual partners and a risk of recurrence. ^[4]

HPV testing of sexual partners is not recommended. Partners are likely to already have HPV infection, even if asymptomatic, and testing does not alter management. ^[4]

Patient-administered topical therapy ^[2][4]

The following options are suitable for external anogenital warts. There is no evidence to support the benefit of one treatment option over another; use shared decision-making.

• Imiquimod cream ^[2][4][16]
• Podofilox solution or gel ^[2][4][16]
• Sinecatechins 15% ointment ^[2][4][16]

Topical application of imiquimod and sinecatechins may reduce the efficacy of barrier contraception; inform patients of this risk and provide alternative contraception as needed. ^[4]

Provider-administered therapies ^[2][4]

Depending on the location of the warts, specialist referral (e.g., gynecologist, colorectal specialist, urologist) is recommended. Treatment may be combined with patient-administered topical therapy.

• For internal or external anogenital warts
  • Topical trichloroacetic acid (TCA) OR bichloroacetic acid (BCA) ^[4]
  • Cryotherapy
  • CO₂laser surgery
  • Electrocautery
  • Tangential excision
• For urethral meatus warts
  • Cryotherapy
  • Surgical excision

To prevent aerosolized transmission of HPV to the upper respiratory tract, perform electrocauterization of warts in an adequately ventiled area with appropriate PPE (e.g., N95 or above grade respirator). ^[17]

Anogenital warts in pregnancy ^[4][16]

Anogenital warts may increase in number and become friable during pregnancy. ^[4]

• Diagnostics: similar to diagnostics for anogenital warts in nonpregnant individuals
• Treatment
  • Consider delaying treatment until after delivery. ^[4]
  • The following options are considered safe during pregnancy: ^[4][16]
    • Topical TCA or BCA ^[2][4][16]
    • Cryotherapy
    • Surgical ablation or excision ^[16]
• Obstetric management ^[4][16]
  • Genital warts are not a routine indication for cesarean delivery. ^[4]
  • Consider cesarean delivery if:
    • Warts are large enough to potentially obstruct normal vaginal delivery (e.g., giant condylomata)
    • There is a risk of significant bleeding
• Complications: risk of transmission of HPV, including to the infant's respiratory tract (juvenile recurrent respiratory papillomatosis) ^[4]
• Prevention considerations: HPV vaccines are not recommended during pregnancy. ^[4][16][18]

Topical imiquimod, sinecatechins, and podofilox should not be used in pregnancy. ^[4][16]

Anogenital warts in children ^[4][19]

• Routes of transmission
  • Sexual
  • Nonsexual (e.g., perinatal maternal-infant transmission, autoinoculation, skin contact, fomites) ^[19][20]
• Management ^[19]
  • Assess all prepubertal children for possible sexual abuse. ^[19]
  • Consider watchful waiting, as most lesions resolve spontaneously within a few years. ^[20]
  • Treatment options are similar to adults, e.g.: ^[19][21]
    • Off-label use of topical therapies (e.g., imiquimod, podofilox)
    • Cryotherapy, laser, or surgical excision

Anogenital warts in immunocompromised individuals ^[4][16]

Immunocompromised individuals are at an increased risk of multiple and/or large condylomata that may be refractory to treatment.

• Consider biopsy to confirm the diagnosis before treatment. ^[4]
• Management mirrors that of immunocompetent individuals; however, sinecatechins are not recommended. ^[2][4][16]
• See also “Giant condylomata.”

Giant condylomata (Buschke-Löwenstein tumor) ^[22]

• Etiology: HPV infection (primarily types 6 and 11)
• Epidemiology
  • Most commonly occurs in individuals aged 40–50 years ^[23]
  • Often affects immunocompromised individuals
• Clinical features
  • Slow-growing verrucous lesion in the anogenital region
  • Can grow > 10 cm in diameter
  • May be associated with discomfort, bleeding, abscess, or fistula due to local tissue destruction
• Diagnostics ^[23]
  • Diagnosis is based on clinical features and biopsy excluding SCC.
  • Consider imaging (e.g., CT, MRI) to assess disease extent.
• Management ^[22][23][24]
  • Assess for conditions associated with immunodeficiency (e.g., HIV testing).
  • Perform local lymph node examination and obtain biopsy of palpable nodes.
  • Refer for surgical excision with possible neoadjuvant chemoradiation or topical imiquimod.
• Prognosis: Recurrence is common.

• See “Prevention of HPV infection” and “Prevention of STIs.”
• Advise patients on smoking cessation. ^[24]