Management of Genital Warts in Healthy Adults
For external genital warts in otherwise healthy adults, first-line treatment should be either patient-applied podofilox 0.5% solution/gel or imiquimod 5% cream, with provider-administered cryotherapy with liquid nitrogen as an equally effective alternative. 1, 2
Patient-Applied First-Line Options
Podofilox 0.5% (Podophyllotoxin)
- Apply twice daily for 3 consecutive days, followed by 4 days of no therapy, repeating this cycle up to 4 times 1
- Patients use a cotton swab for solution or finger for gel application 1
- Total wart area treated should not exceed 10 cm² and total volume should not exceed 0.5 mL per day 1
- The provider should demonstrate proper application technique at the first visit and identify which warts to treat 1
- Contraindicated in pregnancy 1
- Most cost-effective treatment option available 3
Imiquimod 5% Cream
- Apply at bedtime 3 times per week for up to 16 weeks 1, 2
- Wash treatment area with mild soap and water 6-10 hours after application 1
- Many patients achieve clearance by 8-10 weeks 1
- Achieves 50% complete clearance rate in intent-to-treat analysis, with 19% recurrence rate among those who cleared 2, 4
- Contraindicated in pregnancy 1
- Local inflammatory reactions are common (itching 54%, erythema 33%, burning 31%) but systemic reactions are rare 4
Provider-Administered First-Line Options
Cryotherapy with Liquid Nitrogen
- Apply every 1-2 weeks until clearance 1, 5
- Efficacy ranges from 63-88% with recurrence rates of 21-39% 1, 5
- Relatively inexpensive, requires no anesthesia, and produces no scarring when performed properly 1
- Most patients experience moderate pain during and after the procedure 1
- Cryoprobes should NEVER be used in the vagina due to risk of perforation and fistula formation 1
Trichloroacetic Acid (TCA) 80-90%
- Apply small amount only to warts and allow to dry until white "frosting" develops 1
- Powder with talc or sodium bicarbonate to remove excess unreacted acid 1
- Repeat weekly if necessary 1
- Achieves 81% efficacy with 36% recurrence rate 5
- Too inconsistent to be recommended as primary treatment in some analyses 6
Treatment Selection Algorithm
Choose treatment based on:
- Patient preference (most important factor) 1
- Anatomic site and moisture level (moist/intertriginous areas respond better to topical treatments) 1
- Number and size of warts 1
- Cost and convenience considerations 1
- Patient ability to apply treatment correctly 1
For patients who prefer home treatment and have accessible warts: start with podofilox or imiquimod 1, 7
For patients who prefer office-based treatment or have difficulty with self-application: use cryotherapy 1, 7
When to Change Treatment Strategy
- Switch treatment modality if no substantial improvement after 3 provider-administered treatments 1
- Consider alternative therapy if warts have not completely cleared after 6 treatments 1
- Avoid overtreatment by continuously evaluating the risk-benefit ratio 1
Second-Line and Refractory Disease Options
Podophyllin Resin 10-25%
- Apply to warts and allow to air dry, limiting to ≤0.5 mL or ≤10 cm² per session 1
- Wash off thoroughly 1-4 hours after application 1
- Repeat weekly if necessary 1
- Contraindicated in pregnancy 1
- Less preferred than podofilox due to inconsistent efficacy 6
Surgical Removal
- Reserved for extensive disease or treatment failures 1, 5
- Achieves 93% efficacy with 29% recurrence rate 1, 5
- More effective than cryotherapy but requires anesthesia and has higher morbidity 6
Electrodesiccation/Electrocautery
- Contraindicated in patients with cardiac pacemakers 1
- Contraindicated for lesions proximal to the anal verge 1
Site-Specific Considerations
Vaginal Warts
- Use cryotherapy with liquid nitrogen spray (NOT cryoprobe) or TCA 80-90% 1
- Never use cryoprobe due to perforation risk 1
Urethral Meatus Warts
- Cryotherapy with liquid nitrogen or podophyllin 10-25% 1
- Limited data support use of podofilox and imiquimod in select patients 1
Anal Warts
- External perianal warts: cryotherapy, TCA 80-90%, or surgical removal 1
- Intra-anal/rectal mucosal warts require specialist referral 1, 5
Critical Pitfalls to Avoid
- Do not use expensive therapies, toxic therapies, or procedures causing scarring for limited disease 1
- Avoid interferon therapy—it is expensive, has high adverse effects, and is no more effective than other options 1
- Do not use 5-fluorouracil cream—it lacks controlled study evidence and causes frequent local irritation 1
- Refer extensive or refractory disease to an expert rather than continuing ineffective treatment 1
- Scarring (hypopigmentation/hyperpigmentation) is common with ablative modalities 1
- Rare but serious complications include chronic pain syndromes (vulvodynia, hyperesthesia) 1
Natural History and Patient Counseling
- 20-30% of untreated genital warts resolve spontaneously within 3 months 1, 5
- Recurrence is common (approximately 30%) regardless of treatment method, typically within first 3 months 1
- Treatment removes visible warts but does not eliminate HPV infection 1, 8
- HPV types 6 and 11 cause >90% of genital warts and are low-risk types not associated with cancer 5, 8
- Patients may remain infectious even after wart clearance 1
- Latex condom use may reduce but does not eliminate transmission risk 1
Special Populations
Pregnancy
- Use only cryotherapy or TCA—avoid imiquimod, podofilox, and podophyllin 1
- Many experts advocate removal during pregnancy as warts can proliferate and become friable 1
- Cesarean delivery should not be performed solely to prevent HPV transmission 1
Immunosuppressed Patients
- May not respond as well as immunocompetent persons 1
- Higher recurrence rates expected 8
- Standard treatments should still be attempted 9