What is the best treatment for genital warts caused by human papillomavirus (HPV)?

Treatment of Genital Warts

For most patients with genital warts, start with patient-applied podofilox 0.5% solution/gel or imiquimod 5% cream as first-line therapy, reserving provider-administered cryotherapy with liquid nitrogen for those who prefer office-based treatment or cannot self-apply medications. 1

Understanding Treatment Goals and Limitations

The primary goal of treating genital warts is removal of symptomatic visible warts and addressing cosmetic concerns—not HPV eradication. 2 No currently available treatment eliminates the virus from surrounding tissue or affects the natural history of HPV infection. 3 Treatment may or may not decrease infectivity, and there is no evidence that treating visible warts affects cervical cancer development. 2, 3

Important context: 20-30% of genital warts resolve spontaneously within 3 months without any intervention, though they may also remain unchanged or increase in size/number. 4, 3 Recurrence occurs in approximately 25-30% of cases regardless of treatment modality due to reactivation of subclinical infection. 1, 3

First-Line Patient-Applied Treatments

Podofilox 0.5% Solution or Gel

• Apply twice daily for 3 consecutive days, followed by 4 days off therapy. 1
• Repeat this cycle up to 4 times until warts clear. 1
• Total treatment area must not exceed 10 cm² of wart tissue and total volume not exceed 0.5 mL per day. 1
• Contraindicated in pregnancy. 3
• FDA-approved specifically for external genital warts, not for perianal or mucous membrane warts. 5

Imiquimod 5% Cream

• Apply 3 times per week for up to 16 weeks until complete clearance. 1
• Works as a topically active immune enhancer that stimulates interferon and cytokine production. 1
• Many patients achieve clearance by 8-10 weeks. 1
• Works better on moist surfaces and intertriginous areas than dry surfaces. 3
• Contraindicated in pregnancy. 3

Sinecatechins 15% Ointment

• Apply three times daily until complete clearance, but not longer than 16 weeks. 1
• Contains green tea extract and catechins as active ingredients. 1
• May weaken condoms and diaphragms. 1

First-Line Provider-Administered Treatments

Cryotherapy with Liquid Nitrogen

• Most common provider treatment with 63-88% efficacy and 21-39% recurrence rates. 1, 4
• Destroys warts by thermal-induced cytolysis. 1
• Repeat every 1-2 weeks as necessary. 1, 4
• Relatively low cost with no requirement for anesthesia. 1
• Does not cause scarring when performed properly. 4
• Safe in pregnancy. 3

Trichloroacetic Acid (TCA) or Bichloroacetic Acid (BCA) 80-90%

• Destroys warts by chemical coagulation of proteins. 1
• Apply only to warts (not surrounding tissue) and allow to dry until white "frosting" develops. 4
• Can be neutralized with soap, sodium bicarbonate, or talc if pain is intense. 1, 4
• Repeat weekly if necessary, up to 6 applications maximum. 4
• Achieves 81% efficacy with 36% recurrence rate. 4
• Safe in pregnancy. 3

Treatment Selection Algorithm

Choose treatment based on:

• Wart location: Moist surfaces/intertriginous areas respond better to topical treatments; drier surfaces may require ablative therapy. 2, 3
• Number and size: Small warts present less than 1 year respond better to treatment. 3
• Patient ability and preference: Patient-applied therapies require compliance with multi-week regimens; provider-administered options suit those preferring office visits. 1, 3
• Pregnancy status: Use only cryotherapy or TCA; avoid podofilox, podophyllin, imiquimod, and sinecatechins. 3
• Cost and convenience: Patient-applied options reduce office visits but require sustained adherence. 3

When to Change Treatment

Switch treatment modality if: 1, 3

• No substantial improvement after 3 provider-administered treatments
• No substantial improvement after 8 weeks of patient-applied therapy
• Warts have not completely cleared after 6 provider-administered treatments

Most genital warts respond within 3 months of therapy. 2

Site-Specific Considerations

Cervical Warts

• Require biopsy evaluation to exclude high-grade squamous intraepithelial lesions before treatment. 1
• Management should include consultation with a specialist. 1

Vaginal Warts

• Treat with cryotherapy using liquid nitrogen (cryoprobe not recommended due to perforation/fistula risk). 1
• Alternatively, use TCA/BCA 80-90% applied weekly. 1

Urethral Meatus Warts

• Treat with cryotherapy using liquid nitrogen. 1
• Alternatively, use podophyllin 10-25% in compound tincture of benzoin (contraindicated in pregnancy). 1

Anal Warts

• External anal warts can be treated with cryotherapy, TCA, or surgical removal in primary care. 1, 4
• Intra-anal warts require specialist consultation and management. 1, 4

Surgical Options for Extensive or Refractory Disease

• Surgical removal, electrocautery, or laser therapy achieve 93% efficacy with 29% recurrence rate. 1
• Reserved for patients with large number/area of warts or treatment failures. 1, 4
• After local anesthesia, warts can be destroyed by electrocautery, tangential excision with scissors/scalpel, laser, or curettage. 1

Common Pitfalls and Complications

• Persistent hypopigmentation or hyperpigmentation occurs commonly with ablative modalities and immune-modulating therapies. 2
• Depressed or hypertrophic scars are uncommon but can occur, especially with insufficient healing time between treatments. 2
• Disabling chronic pain syndromes (vulvodynia, hyperesthesia) or painful defecation/fistulas with anal warts occur rarely. 2
• Avoid overtreatment by evaluating risk-benefit ratio throughout therapy. 2

Patient Counseling

• HPV types 6 and 11 cause over 90% of genital warts and are low-risk types that do not cause cancer. 4, 3
• Treatment targets visible warts but does not eliminate the underlying virus. 4, 3
• Recurrence is common (approximately 30%) regardless of treatment method due to viral reactivation, not partner reinfection. 3