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

Treatment of Male HPV Infection

There is no treatment for HPV infection itself in men—only the visible manifestations (genital warts) can be treated, while subclinical HPV infection clears spontaneously in most cases without intervention. 1, 2

Understanding HPV in Men

The fundamental principle is that treatment targets visible warts only, not the underlying virus, which cannot be eradicated with current therapies. 2, 3 Most HPV infections (70-80%) clear spontaneously within 1-2 years through natural immune responses. 1 Without treatment, genital warts may resolve spontaneously in 20-30% of cases within 3 months, remain unchanged, or increase in size/number. 2, 3

Treatment Goals and Limitations

• The primary goal is removal of symptomatic visible warts and amelioration of symptoms—not HPV eradication. 2, 3
• Treatment induces wart-free periods but does not eliminate the virus from surrounding tissue. 2
• No evidence indicates that treating genital warts reduces transmission risk or affects cancer development in partners. 2, 3
• Recurrence rates are high (at least 25-30%) with all treatment modalities, typically within 3 months, due to reactivation of subclinical infection rather than reinfection. 2, 3

First-Line Treatment Options

Patient-Applied Therapies

Podofilox 0.5% solution or gel:

• Apply twice daily for 3 consecutive days, followed by 4 days of no therapy. 2, 3
• Repeat cycle up to 4 times. 2
• Contraindicated in pregnancy. 3

Imiquimod 5% cream:

• Apply 3 times per week for up to 16 weeks. 2
• Continue until warts clear or maximum treatment period reached. 2
• Works better on moist surfaces and intertriginous areas than dry surfaces. 3, 4
• Wash treatment area with mild soap and water 6-10 hours following application. 4
• Contraindicated in pregnancy. 3, 4
• Common side effects include erythema, erosion, excoriation/flaking, and edema. 4

Provider-Administered Therapies

Cryotherapy with liquid nitrogen:

• Preferred first-line provider-administered treatment. 2, 3
• Efficacy of 63-88% with recurrence rates of 21-39%. 3
• Apply every 1-2 weeks as needed. 5

Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80-90%:

• Apply small amount only to warts and allow to dry until white frosting develops. 1, 2
• If excess acid applied, powder with talc, sodium bicarbonate, or liquid soap to remove unreacted acid. 1, 2
• Repeat weekly if necessary. 1, 2
• Safe for use in pregnancy. 3, 5

Second-Line and Surgical Options

Surgical removal is reserved for extensive or refractory warts:

• Options include electrodesiccation/electrocautery, surgical excision, tangential scissor excision, shave excision, or carbon dioxide laser therapy. 2, 3
• Efficacy of 93% with recurrence rate of 29%. 5

Treatment Selection Algorithm

Choose treatment based on:

• Wart characteristics: size, number, location, and morphology. 2, 3
• Small warts present less than 1 year respond better to treatment. 3
• Warts on moist/intertriginous areas respond best to topical treatments (imiquimod, podofilox). 2, 3
• Patient preference and ability to attend office visits. 2, 3
• Cost and convenience considerations. 2
• Pregnancy status (use only cryotherapy or TCA if pregnant). 3, 5

Change treatment modality if:

• No substantial improvement after 3 provider-administered treatments. 3
• Warts have not completely cleared after 6 treatments. 3
• Side effects are severe. 2

Special Populations

HIV-infected men:

• May have larger or more numerous warts. 2
• May not respond as well to therapy and experience more frequent recurrences. 2
• Are at higher risk for squamous cell carcinomas arising in warts. 2

Intra-anal warts:

• Should be managed in consultation with a specialist. 1
• Many persons with anal warts also have rectal mucosal warts, so inspection of rectal mucosa by digital examination, standard anoscopy, or high-resolution anoscopy may be beneficial. 1

Critical Management Pitfalls

If purulent drainage is present:

• Never treat warts in the presence of active purulent infection, as this increases risk of treatment failure, scarring, and systemic complications. 5
• Initiate empiric antibiotic coverage for skin and soft tissue infection (targeting Staphylococcus aureus and Streptococcus species). 5
• Assess for abscess formation requiring incision and drainage before any wart-directed therapy. 5

Avoid:

• Extensive or aggressive treatment that may result in scarring, chronic pain syndromes, or painful defecation. 5
• Extending treatment period beyond recommended duration due to missed doses or rest periods. 4

Prevention Strategies

HPV vaccination:

• The quadrivalent HPV vaccine (Gardasil) prevents infection with HPV types 6 and 11 (which cause 90% of genital warts). 1, 2
• Recommended for males aged 9-26 years, even if already diagnosed with HPV. 1, 2
• Most effective when all doses administered before sexual contact. 1

Risk reduction:

• Consistent condom use may reduce but not eliminate transmission risk, as HPV can infect areas not covered by condoms. 1, 2
• Sexual contact should be avoided while imiquimod cream is on the skin. 4

Essential Patient Counseling

• HPV types 6 and 11 cause over 90% of genital warts and are low-risk types that do not cause cancer. 3, 5
• Genital warts are not life-threatening and except in very rare cases will not turn into cancer. 1
• HPV diagnosis does not indicate sexual infidelity, as infection can be present for many years before detection. 1, 2
• Most recurrences result from reactivation of subclinical infection rather than reinfection by a partner. 2, 3
• Within an ongoing sexual relationship, both partners are usually infected at the time one person is diagnosed, even though signs may not be apparent. 1
• It is unclear whether informing subsequent sex partners about past genital warts diagnosis is beneficial to their health. 1
• No clinically validated HPV test exists for men. 1