What is the recommended treatment for a patient with penile warts due to Human Papillomavirus (HPV) infection?

Treatment of Penile Warts

Primary Treatment Recommendation

For penile warts, treatment should be selected based on patient preference between self-applied options (podofilox 0.5% or imiquimod 5% cream) and provider-administered treatments (cryotherapy with liquid nitrogen or TCA/BCA 80-90%), as no single treatment has proven superior to others for achieving wart clearance. 1

Patient-Applied Treatment Options

Podofilox 0.5% Solution or Gel

• Apply twice daily for 3 consecutive days, followed by 4 days off therapy, repeating this weekly cycle for up to 4 cycles 1, 2
• Limit total treatment area to ≤10 cm² of wart tissue and total volume to ≤0.5 mL per day 1, 2
• The healthcare provider should ideally apply the first treatment to demonstrate proper technique and identify which warts require treatment 1, 2
• This option is relatively inexpensive, easy to use, and safe, with mild to moderate pain or local irritation as expected side effects 1
• Contraindicated in pregnancy 1

Imiquimod 5% Cream

• Apply with a finger at bedtime, 3 times per week (non-consecutive days such as Monday-Wednesday-Friday) for up to 16 weeks 1, 2, 3
• Wash the treatment area with mild soap and water 6-10 hours after application (typically in the morning) 1, 3
• Works as an immune enhancer by stimulating interferon and cytokine production 1, 2
• Contraindicated in pregnancy 1, 4
• Local inflammatory reactions including erythema, irritation, ulceration, and vesicles are common 1

Important caveat for imiquimod in men: Complete clearance rates in males are substantially lower (approximately 35-62%) compared to females (approximately 66-75%), even with optimal dosing 5, 6, 7. More frequent application (daily or multiple times daily) does not improve clearance rates and significantly increases local adverse reactions 5.

Provider-Administered Treatment Options

Cryotherapy with Liquid Nitrogen

• Repeat applications every 1-2 weeks until warts clear 1, 2
• Efficacy ranges from 63-88% in clinical trials 2, 8
• Destroys warts by thermal-induced cytolysis 2
• Requires proper clinical training to avoid complications 8

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

• Apply a small amount only to warts and allow to dry until a white "frosting" develops 1, 8
• Can be repeated weekly if necessary 1, 8
• This is the only topical treatment safe for use during pregnancy 1, 8
• If excess acid is applied, neutralize with talc, sodium bicarbonate, or liquid soap 1

Surgical Removal

• Options include tangential scissor excision, tangential shave excision, curettage, or electrosurgery 1
• Most beneficial for patients with large numbers or extensive areas of genital warts 1
• Eliminates warts at a single visit but requires substantial clinical training and equipment 1

Treatment Selection Algorithm

Choose treatment based on the following factors: 1, 2

1. Wart characteristics: Number, size, and anatomic location (warts on moist surfaces respond better to topical treatments) 1
2. Patient ability: Can the patient identify and reach all warts for self-application? 1
3. Patient preference: Some prefer privacy of home treatment, others prefer provider-administered options 1
4. Pregnancy status: Only TCA/BCA are safe options during pregnancy 1, 8
5. Cost and convenience considerations 1

When to Change Treatment

Switch treatment modality if: 1, 8

• No substantial improvement after 3 provider-administered treatments 1
• No substantial improvement after 8 weeks of patient-applied therapy 8, 4
• Severe side effects develop 1
• Do not extend treatment beyond recommended duration (16 weeks for imiquimod, 4 cycles for podofilox) 2, 4

Critical Treatment Limitations and Expectations

Most genital warts respond within 3 months of therapy 1

Treatment removes visible warts but does not eradicate HPV infection or affect its natural history 2, 8. The reduction in HPV viral DNA from treatment does not clearly reduce future transmission 1.

Recurrence rates are high with all treatment modalities: 13-19% in immunocompetent patients after complete clearance with imiquimod 9, 6, and recurrence rates are similarly elevated across other modalities 8.

Spontaneous resolution is common: 60-80% of untreated warts resolve spontaneously within the first year, making observation without treatment an acceptable alternative for some patients 1, 8.

Common Complications to Warn Patients About

• Persistent hypopigmentation or hyperpigmentation occurs commonly with ablative modalities and has been described with imiquimod 1, 8
• Depressed or hypertrophic scars are uncommon but can occur, especially with insufficient healing time between treatments 1, 8
• Rarely, treatment can result in disabling chronic pain syndromes such as hyperesthesia of the treatment site 1