What are the treatment options for human papillomavirus (HPV) of the penis?

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From the Guidelines

Treatment for penile HPV typically involves a combination of approaches, including patient-applied medications like imiquimod 5% cream or podofilox 0.5% solution/gel, and provider-administered treatments like cryotherapy, trichloroacetic acid, or surgical excision, with the goal of removing visible warts and allowing the immune system to control the viral infection 1.

Treatment Options

  • Patient-applied medications:
    • Imiquimod 5% cream, applied three times weekly for up to 16 weeks
    • Podofilox 0.5% solution/gel, applied twice daily for 3 days, followed by 4 days of no treatment, for up to 4 cycles
  • Provider-administered treatments:
    • Cryotherapy with liquid nitrogen every 1-2 weeks
    • Trichloroacetic acid (TCA) 80-90% applied weekly
    • Surgical excision or electrosurgery for larger lesions

Considerations

  • No single treatment is universally effective, and recurrence rates of 10-30% are common regardless of the method used
  • For subclinical or flat HPV lesions, treatment may not be necessary as many infections clear spontaneously within 1-2 years
  • Partners should be examined for HPV lesions, though condom use provides only partial protection against transmission
  • HPV vaccination is recommended for prevention but does not treat existing infections

Prevention

  • HPV vaccination is recommended for adults up to 45 years old, with the 9-valent vaccine (Gardasil 9) providing protection against the most common high-risk types, as well as types that cause anogenital warts 1
  • Correct and consistent use of condoms can lower the chances of giving or getting genital HPV, but is not fully protective 1

From the FDA Drug Label

In a double-blind, placebo-controlled clinical study, 209 otherwise healthy subjects 18 years of age and older with genital/perianal warts were treated with imiquimod cream or vehicle control 3 times per week for a maximum of 16 weeks.

Data on complete clearance are listed in the table below. The median time to complete wart clearance was 10 weeks

Table 14: Complete Clearance Rates (External Genital Warts) – Study EGW1 Treatment Subjects with Complete Clearance of Warts Subjects Without Follow-up Subjects with Warts Remaining At Week 16 Overall Imiquimod Cream (n=109) 54(50%) 19(17%) 36(33%) Vehicle (n=100) 11(11%) 27(27%) 62(62%) Females Imiquimod Cream (n=46) 33(72%) 5(11%) 8(17%) Vehicle (n=40) 8(20%) 13(33%) 19(48%) Males Imiquimod Cream (n=63) 21(33%) 14(22%) 28(44%) Vehicle (n=60) 3(5%) 14(23%) 43(72%)

The treatment options for human papillomavirus (HPV) of the penis include imiquimod cream, which has been shown to have a complete clearance rate of 50% in a clinical study of external genital warts 2.

  • Key points:
    • Imiquimod cream is applied 3 times per week for a maximum of 16 weeks.
    • The median time to complete wart clearance was 10 weeks.
    • Complete clearance rates were higher in females (72%) compared to males (33%) 2.

From the Research

Treatment Options for HPV of the Penis

  • Destruction and excision of lesions are the main treatment options for human papillomavirus (HPV) 3
  • Prophylactic HPV vaccination has proven its efficacy against cervical cancer and may also partially prevent penile cancer 4
  • Therapeutic HPV vaccines, which generate T cell-mediated immunity against HPV infection, are being developed to treat existing HPV infections 5

Topical Treatments

  • Imiquimod, an immune response modifier, has shown efficacy in treating HPV-related genital intraepithelial neoplasia, with complete response rates ranging from 5 to 88% 6
  • Imiquimod 5% cream has been used to treat persistent HPV infection after surgical therapy for cervical or vaginal intraepithelial neoplasia, with 76.3% of patients clearing the infection 7

Vaccine Development

  • Several types of therapeutic HPV vaccine candidates have been developed, including live-vector, protein, peptide, dendritic cell, and DNA-based vaccines 5
  • These vaccines target HPV oncoproteins E6 and E7 to generate a cell-mediated immune response against HPV 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

HPV: diagnosis, prevention, and treatment.

Clinical obstetrics and gynecology, 2012

Research

Vaccination Strategies for the Control and Treatment of HPV Infection and HPV-Associated Cancer.

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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