What are the treatment options for a patient with Human Papillomavirus (HPV) warts?

Treatment Options for HPV Warts

For external genital warts, treatment choice depends on whether the patient can self-apply therapy: offer patient-applied options (podofilox 0.5% or imiquimod 5%) for accessible warts, or provider-administered treatments (cryotherapy with liquid nitrogen or TCA/BCA 80-90%) when self-application is not feasible or preferred. 1, 2

Patient-Applied Treatments (First-Line for Accessible Warts)

Podofilox 0.5% Solution or Gel

• Apply twice daily for 3 consecutive days, followed by 4 days off therapy 3, 4
• Repeat this weekly cycle for up to 4 cycles as needed 3, 4
• Limit treatment area to ≤10 cm² of wart tissue and ≤0.5 mL total volume per day 3, 2
• This antimitotic drug destroys warts through direct cytotoxic effects 1
• Relatively inexpensive, easy to use, with mild to moderate pain or local irritation as common side effects 3, 1
• Contraindicated in pregnancy 3, 2
• The provider should ideally demonstrate proper application technique at the first visit 3, 2

Imiquimod 5% Cream

• Apply with a finger at bedtime, 3 times per week (non-consecutive days) for up to 16 weeks 3, 5, 6
• Wash treatment area with mild soap and water 6-10 hours after application 3, 5, 6
• Works as an immune enhancer, stimulating interferon and cytokine production 3, 1
• Complete clearance occurs in 37-50% of patients, with higher rates in women than men 7
• Local inflammatory reactions (erythema, itching, burning) are common but usually mild to moderate 3, 7
• May weaken condoms and vaginal diaphragms 1
• Contraindicated in pregnancy 3, 5

Imiquimod 3.75% Cream (Alternative Formulation)

• Apply once daily for up to 8 weeks 3
• Clearance rates of 27-29% at 16 weeks post-treatment initiation 3
• Similar side effect profile to 5% formulation but with daily application 3

Provider-Administered Treatments (First-Line When Self-Application Not Feasible)

Cryotherapy with Liquid Nitrogen

• Repeat applications every 1-2 weeks until warts clear 3, 2
• Destroys warts by thermal-induced cytolysis 3, 1
• Efficacy ranges from 63-88% in clinical trials 3, 1
• Does not require anesthesia and does not result in scarring if performed properly 1, 2
• Pain after application, followed by necrosis and sometimes blistering, is common 3
• Proper training is essential—over-treatment or under-treatment reduces efficacy and increases complications 3

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

• Apply small amount only to warts and allow to dry until white "frosting" develops 3, 2
• If excess acid applied, powder with talc, sodium bicarbonate, or liquid soap to remove unreacted acid 3
• Repeat weekly if necessary 3, 2
• Can be used in pregnancy, unlike other topical agents 2
• Destroys warts by chemical coagulation of proteins 3

Surgical Removal

• Options include tangential scissor excision, tangential shave excision, curettage, or electrosurgery 3, 1
• Appropriate for patients seeking immediate clearance 1
• Requires proper personal protective equipment (goggles, masks, smoke evacuators) during electrosurgical procedures due to HPV DNA in smoke plumes 3

Alternative Treatments (Second-Line)

Podophyllin Resin 10-25%

• Apply to each wart and allow to air dry before contact with clothing 3
• Limit application to ≤0.5 mL or ≤10 cm² per session 3
• Wash off thoroughly 1-4 hours after application to reduce local irritation 3
• Repeat weekly if necessary 3
• Should be considered alternative therapy only due to severe toxicity reports with misuse, including death and fetal loss 3
• Contraindicated in pregnancy 3

Intralesional Interferon or Laser Surgery

• Reserved as alternative options 3

Treatment Selection Algorithm

Warts on moist surfaces or intertriginous areas respond better to topical treatments than warts on drier surfaces 3, 1

Consider these factors when selecting treatment:

• Patient ability to identify and reach warts for self-treatment 3, 1
• Wart size, number, and anatomic location 1, 2
• Patient preference for office visits versus home treatment 1, 2
• Cost and convenience 2
• Pregnancy status (TCA/BCA are the only safe options) 2

When to Change Treatment

Change treatment modality if the patient has not improved substantially after 3 provider-administered treatments or 8 weeks of patient-applied therapy 1, 2

Do not extend treatment beyond recommended duration: 16 weeks for imiquimod, 4 cycles for podofilox 1

Critical Warnings and Limitations

Treatment removes visible warts but does not eradicate HPV infection or affect its natural history 1, 2

Recurrence rates are high with all treatment modalities 2

• Untreated warts may resolve spontaneously (60-80% in first year), remain unchanged, or increase in size/number 3, 1, 2
• Persistent hypopigmentation or hyperpigmentation is common and may be permanent 1
• Depressed or hypertrophic scars are rare but can occur, especially with insufficient healing time between treatments 1
• Disabling chronic pain syndromes (vulvodynia, hyperesthesia) can occur rarely 1

Common Pitfalls to Avoid

• Do not over-apply podofilox or podophyllin—systemic absorption can cause severe toxicity 3
• Ensure proper drying of podophyllin before skin-to-skin contact to prevent spread to adjacent areas 3
• With cryotherapy, avoid over-treatment or under-treatment through proper training 3
• Allow adequate healing time between treatments to prevent scarring 1
• Do not use cryoprobe in vagina due to risk of perforation and fistula formation 3

Site-Specific Considerations

Vaginal Warts

• Cryotherapy with liquid nitrogen (not cryoprobe) or TCA/BCA 80-90% 3

Urethral Meatus Warts

• Cryotherapy with liquid nitrogen or podophyllin 10-25% 3

Anal Warts

• Cryotherapy, TCA/BCA 80-90%, or surgical removal 3
• Intra-anal warts require specialist consultation 3