Anogenital Warts

Anogenital warts (condylomata acuminata) are benign epithelial proliferations of the anogenital skin and mucosa caused by low-risk human papillomavirus, most often types 6 and 11 (over 90% of cases).

They are the commonest clinical manifestation of genital HPV infection and one of the most frequently diagnosed viral STIs, with an incidence of about 1 in 1,000 people per year in high-income countries, peaking in those aged 20 to 24.

Spread by skin-to-skin contact during vaginal, anal or oral sex, and through autoinoculation and perinatal exposure (risk of juvenile-onset recurrent respiratory papillomatosis).

Transmission to partners occurs in about 65% after contact with an infected person. Incubation averages 3 months (range of weeks to 8 months or more).

Natural history: 20 to 30% regress spontaneously in 3 months, about 50% in 1 year, with recurrence in 20 to 50% after treatment, mainly from persistent latent virus in adjacent skin.

Risk factors: multiple partners, early sexual debut, immunosuppression (HIV, transplant), smoking, pregnancy (growth), other STIs, MSM (anal warts), and lack of HPV vaccination.

Pathology: epidermal hyperplasia (acanthosis, papillomatosis), hyperkeratosis or parakeratosis, and koilocytes (vacuolated keratinocytes with raisin-like nuclei). No dysplasia in typical warts (low-risk HPV).

Special entities

• Giant condyloma (Buschke-Löwenstein tumour): locally destructive verrucous carcinoma, large cauliflower mass, mostly HPV 6 and 11, recurring after excision, with potential malignant transformation.

• Bowenoid papulosis: HPV 16-associated pigmented papules (high-grade intraepithelial neoplasia, usually regresses).

• Anal canal warts, meatal and intraurethral warts, vaginal and cervical warts, and oral warts.

• Impact: psychological distress (anxiety, shame, relationship difficulties), cost, and need for repeated treatments.

Presentation is usually painless

• Flesh-coloured, pink or hyperpigmented papules (smooth, dome-shaped), flat-topped plaques (macular or papular), filiform or pedunculated lesions, and cauliflower-like masses. Single or multiple, discrete or confluent.
• Sites: penis (corona, frenulum, prepuce, shaft, meatus), scrotum, vulva (labia, introitus, fourchette), vagina, cervix, perineum, perianal skin, anal canal, pubic area, groin, and rarely mouth. Intra-anal warts are present in about 50% of people with perianal warts.
• Symptoms: itching, burning, bleeding, discharge, irritation or pain, difficulty with hygiene and intercourse, malodour, urinary spraying (meatal warts), obstruction (large lesions). Many are asymptomatic.
• Pregnancy and immunosuppression: more florid, rapidly growing warts.

Differential diagnosis

• Normal variants: pearly penile papules, vestibular papillae, sebaceous glands (Fordyce spots).
• Molluscum contagiosum, condylomata lata (secondary syphilis, moist flat), skin tags, seborrhoeic keratoses, lichen planus, lichen nitidus, Bowenoid papulosis, vulval or penile intraepithelial neoplasia, squamous cell carcinoma, melanocytic naevi, and angiokeratomas.
• Red flags prompting biopsy: pigmented, indurated, fixed, ulcerated or bleeding lesions, atypical appearance, immunocompromise, age over 40 at new onset, lesions that fail to respond to standard therapy, or that worsen during treatment.

• Diagnosis is clinical, by visual inspection with good lighting. Magnification (colposcope or hand lens) helps.
• Biopsy (punch or shave) for atypical features, uncertain diagnosis, or before ablative therapy in immunosuppressed or older patients.
• Acetic acid 3 to 5% application is not recommended for diagnosis (poor specificity).
• HPV typing is not recommended for external genital warts (does not alter management).
• Anal examination: digital rectal examination and anoscopy for perianal warts and anal symptoms (intra-anal warts need anoscopy, and high-resolution anoscopy in high-risk groups).
• Meatal and urethral warts: examine the meatus, and perform urethroscopy for proximal extension.
• Women: speculum examination of the vagina and cervix, with cervical screening per guidelines (the presence of warts does not alter cervical screening schedules, but colposcopy is advised for abnormal cytology).
• Test for other STIs: HIV, syphilis serology (condylomata lata differentiation), chlamydia and gonorrhoea NAAT, hepatitis B vaccination status, and pregnancy test.
• Children: warts in a young child may arise from perinatal transmission (up to age 3 years) or autoinoculation, but consider sexual abuse, with a child protection assessment where suspicious.

Goals: remove symptomatic or visible warts, relieve psychological distress, and reduce transmission. Treatment does not eradicate HPV, and spontaneous clearance occurs in many. Reasonable observation is an option for asymptomatic warts. No single treatment is best. Complete clearance rates are 50 to 90%, recurrence 20 to 50% within 3 to 6 months.

Patient-applied treatments (for external warts, usually small, accessible)

• Podophyllotoxin 0.5% solution or gel, or 0.15% cream: applied twice daily for 3 consecutive days, then 4 days off, for up to 4 cycles (5 for the solution). Total area under 10 cm2, volume under 0.5 mL daily. Local irritation, erosion and pain are common. Avoid in pregnancy.
• Imiquimod 5% cream: applied three times weekly at night, washed off after 6 to 10 hours, for up to 16 weeks (3.75% cream daily for up to 8 weeks). Local inflammatory reactions and hypopigmentation. Avoid in pregnancy. Immune response modifier with lower recurrence (about 13 to 19%).
• Sinecatechins 15% ointment (green tea extract): applied three times daily for up to 16 weeks, not to be used on internal mucosal surfaces or in immunosuppressed. Local reactions.

Clinician-applied treatments

• Cryotherapy with liquid nitrogen (spray or cryoprobe): freezing for 10 to 30 seconds until a 1 to 2 mm halo of white appears, repeated every 1 to 2 weeks for up to 4 to 6 sessions. Clearance 60 to 90%. Safe in pregnancy. Risk of pain, blistering and hypopigmentation.
• Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80 to 90%: applied weekly with a cotton-tipped applicator, neutralised with sodium bicarbonate or talc if excess. Safe in pregnancy and for vaginal and anal canal warts. Pain and ulceration.
• Podophyllin resin 10 to 25% in tincture of benzoin: applied weekly, washed off after 1 to 4 hours. Not for pregnancy, and risk of systemic toxicity if large areas used.
• Surgical: tangential shave excision, curettage, scissor excision, electrosurgery or electrocautery, and CO2 laser ablation under local (lidocaine 1% with adrenaline) or general anaesthesia. Suitable for large, multiple, intraurethral, or resistant warts, with immediate clearance (rates 90%+) and recurrence 20 to 30%. Care to avoid scarring or stricture.
• Intralesional therapies: interferon alpha-2b 1 million IU per wart, three times weekly for 3 weeks, 5-fluorouracil 5% cream or intralesional injection (not for pregnancy), Candida antigen or MMR vaccine injection (immunotherapy, 0.1 to 0.3 mL into the largest wart every 2 to 4 weeks), cidofovir 1% topical for resistant warts, and bleomycin intralesional 0.5 to 1 unit/mL for recalcitrant warts.
• Photodynamic therapy with 5-aminolevulinic acid for recurrent or intra-anal warts.

Site-specific management

• Perianal and anal canal warts: TCA, cryotherapy, surgical excision, electrocautery, infrared coagulation, or imiquimod. Intra-anal warts require anoscopy.
• Meatal warts: cryotherapy, podophyllotoxin (if visible), or TCA. Intraurethral warts: laser or electrocautery by a urologist, or topical 5-fluorouracil 5% instillation.
• Vaginal and cervical warts: cryotherapy or TCA (not podophyllin). Cervical warts require colposcopy and biopsy to exclude high-grade neoplasia.
• Oral warts: cryotherapy or surgical removal.
• Pregnancy: treat if symptomatic with cryotherapy, TCA or surgery. Warts may enlarge, so treatment in the second trimester is reasonable, and delivery may be delayed (until after birth). Cesarean delivery is not indicated for HPV prevention, only if the warts obstruct the birth canal or risk heavy bleeding. Babies should be monitored for respiratory papillomatosis (rare).
• Immunocompromised patients: more resistant and recurrent disease. Combination therapy, antiretroviral therapy optimisation, regular monitoring for dysplasia, and biopsy of atypical lesions. Cidofovir 1% as a topical for resistant lesions.
• Giant condyloma: wide surgical excision with margin and histology, with adjuvant chemo-radiotherapy if carcinoma is found.

Prevention and counselling

• HPV vaccination (the 9-valent vaccine prevents over 90% of HPV-related warts), including after treatment for warts (to protect against other types), at ages 9 to 26 (to 45 by shared decision-making). Vaccine effectiveness against warts: 90% reduction in vaccinated cohorts, with herd protection.
• Condom use reduces risk by about 60%, but does not fully prevent transmission, as warts may be in uncovered areas. Smoking cessation improves clearance.
• Reassurance: warts are common, benign, and not an indicator of cancer risk, and recurrence is due to latent virus. New partners risk infection, and long-term partners usually share the virus, so partner screening is optional. Partners may be examined and offered vaccination.
• Avoid sexual contact during treatment until lesions are clear. Cervical screening continues at regular intervals.

Follow-up

Review every 2 to 4 weeks during treatment, to monitor response, adherence and adverse effects. If no improvement after 3 months, change therapy and reconsider diagnosis (biopsy). After clearance, review at 3 months (peak recurrence) and then as needed. Provide written information and psychosexual support.