eMedicine Specialties > Infectious Diseases > Sexually Transmitted Diseases

Papillomavirus: Treatment & Medication

Author: John D Shanley, MD, MPH, Professor Emeritus, University of Connecticut; Professor of Preventive Medicine, Stony Brook Medical Center
Contributor Information and Disclosures

Updated: Aug 15, 2007

Treatment

Medical Care

Both provider-applied treatments and patient-applied treatments are available. Medical treatments (eg, interferon injection) have been tried, with mixed success. Lesions often recur after treatment, requiring recurrent treatment. Many lesions spontaneously regress. No effective antiviral agents are currently available to treat papillomavirus infections. The US Food and Drug Administration (FDA) has recently approved a vaccine for HPV types 6, 11, 16, and 18.

Surgical Care

Surgical ablation methods include cryotherapy, electrocautery, curettage, and tangential excision. Cryosurgery is the local application of liquid nitrogen to freeze the lesion. The area blisters and sloughs. Monitor for secondary cellulitis.

The location, size, or extent of the lesion and the potential for malignant transformation largely dictate treatment. Uncomplicated lesions can be treated with chemical ablation, cryoablation, surgical excision, or laser treatment. Because the virus is present in the basal layer of the epidermis in a latent state, recurrences are common and retreatment may be necessary.

Consultations

Consultation with a dermatologist may be indicated in some situations. For potentially malignant papilloma infections that involve the genital tract, consultation with a gynecologist or urologist may be indicated. A proctologist may be consulted for individuals with perianal or anal warts. This is especially true for individuals infected with HIV. An otolaryngologist (ENT) should be consulted for patients with papilloma infections involving the larynx.

Medication

The medications used to treat papillomavirus infections primarily are designed to ablate the lesion because of their corrosive properties.

Antimitotics

Treatment of anogenital warts results in necrosis of visible wart tissue. The exact mechanism of action is unknown. Genital warts are epidemiologically associated with cervical carcinoma.


Podofilox (Condylox, Podophyllotoxin)

Topical antimitotic that can be synthesized chemically or purified from plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum).
Limit treatment to <10 cm2 of wart tissue and to <0.5 mL of solution per day. This is a patient-applied therapy.

Adult

0.5% solution or gel applied qod for 3 wk or bid for 3 d qwk for 2-4 wk

Pediatric

Not established

Documented hypersensitivity; mucous membranes

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid contact with eyes; if eye contact occurs, immediately flush eye with copious quantities of water and seek medical advice; not for use on mucous membranes of genital area, including urethra, rectum, and vagina; do not exceed frequency of application or duration of usage; flammable, keep away from open flames


Podophyllum resin (Pod-Ben-25, Podofin)

Cytotoxic agent that results in necrosis when applied to anogenital warts. Arrests mitosis in metaphase; active agent is podophyllotoxin. It is a powdered mixture of resins removed from Mayapple or Mandrake (Podophyllum peltatum Linne). American podophyllum contains one fourth of the amount of the Indian source.
Only a trained medical professional can apply it, and it cannot be dispensed to a patient.

Adult

Apply once per wk for 4 wk, wash off 4-6 h after application; treat only intact lesions

Pediatric

Not established

Documented hypersensitivity; diabetes; impaired peripheral circulation; exuberant lesions with large surface area

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Powerful caustic and severe irritant; do not use if surrounding tissue is swollen or irritated; 25% solution should not be applied near mucous membranes; do not use large amounts; avoid contact with cornea; treated areas may mimic cancer, so biopsy obtained after treatment must be reviewed carefully; topical use has been demonstrated to result in paresthesias, polyneuritis, paralytic ileus, fever, leukopenia, thrombocytopenia, and death; avoid use on mucous membranes, eyes, bleeding warts, moles, birthmarks, or unusual warts with hair

Antineoplastic agents

These are topical preparations that contain the fluorinated pyrimidine 5-fluorouracil. These are antineoplastic and antimetabolite agents.


Fluorouracil (Efudex)

Primary indication of 5-fluorouracil is topical treatment of actinic keratoses. Not FDA-approved for treatment of warts; however, has been used in adults.
Solution contains either 2% or 5% fluorouracil in propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, paraben, and disodium edetate. Cream is 5% in white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60, and paraben.
When applied to lesion, the area undergoes a sequence of erythema, vesiculation, desquamation, erosion, and reepithelialization.

Adult

Not FDA-approved for treatment of warts
5% cream applied topically to the vulva or vagina qd for 5-7 d

Pediatric

Not established

Documented hypersensitivity; potentially serious infections

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May cause significant discomfort; incidence of inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction; recurrence rate is high, and painful ulcers and scarring may occur; may cause photosensitivity with significant discomfort; may cause increased adsorption through inflamed skin; apply with gloves or a nonmetallic applicator

Desiccants

Trichloroacetic acid is a highly corrosive desiccating agent that is used to burn lesions.


Trichloroacetic acid 85% (Tri-Chlor)

Cauterizes skin, keratin, and other tissues. Although caustic, causes less local irritation and systemic toxicity than other agents in the same class. However, response often is incomplete, and reoccurrence is frequent.

Adult

Apply directly to wart qwk by a trained health care professional; may be used on vulva, vagina, anus, and cervix

Pediatric

Apply as in adults

Documented hypersensitivity; not for use on premalignant or malignant lesions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

External use only; restrict use only to treatment areas

Interferons

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alfa, beta, and gamma interferons may be administered topically, systemically, and intralesionally.


Interferon alfa-n3 (Alferon N)

Protein product manufactured by recombinant DNA technology that uses a genetically engineered Escherichia coli bacterium. Mechanisms by which it exerts antiviral activity are not clearly understood. However, modulation of the host immune response may play an important role.

Adult

Suggested dosing: 0.05 mL (250,000 IU) per wart, twice weekly for up to 8 wk; maximum recommended dose per treatment session is 0.5 mL (2.5 million IU); inject into base of each wart, preferably using a 30-gauge needle
For large warts: May be injected at several points around the periphery of the wart, using a total dose of 0.05 mL per wart

Pediatric

Not established

Potential risk of renal failure when administered concurrently with interleukin-2; theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects of interferon alfa; zidovudine and vinblastine may increase toxicity

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

Depression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage has been reported in association with alfa interferon therapy; prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if a patient's wart does not respond within 6 mo, discontinue treatment; if a response occurs, continue treatment until no further improvement is observed and these laboratory parameters have been stable for about 3 mo; whether continued treatment after that time is beneficial is not known

Immunostimulants

These agents stimulate key factors of the immune system.


Imiquimod (Aldara)

Imidazoquinolinamine derivative with no in vitro antiviral activity but does induce macrophages to secrete cytokines (eg, IL-2, IFN-g). Imiquimod has been studied extensively and is a new therapy relative to other external genital wart (EGW) treatments.
Imiquimod has been studied extensively and is a new therapy relative to other EGW treatments.
Dispensed as an individual dose. Patients are advised to wash affected area with mild soap and water upon awakening and to remove residual drug.

Adult

Apply topically as a 5% cream to affected area hs 3 times/wk for up to 16 wk

Pediatric

Not established

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

Genital use: Not recommended for treatment of rectal, cervical, intravaginal, urethral, and intra-anal human papilloma infection; following surgery or drug treatment, do not use topical imiquimod until genital/perianal tissue is healed
Actinic keratosis: Avoid exposure to sunlight or artificial tanning; regular use of sunscreen is encouraged; avoid contact with lips, eyes, and nostrils; common adverse effects include erythema, edema, vesicles, erosion or ulceration, weeping, exudate, flaking, scaling, dryness, and scabbing or crusting
Basal cell carcinoma: Medical follow-up is essential to ensure cancer has responded adequately to treatment; may cause redness, swelling, and sore development at application site; may cause itching or burning

Vaccines

A human papillomavirus vaccine is now available for the prevention of HPV-associated dysplasias and neoplasia, including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions. Girls and young women aged 9-26 years should receive the complete immunization series.


Papillomavirus vaccine (Gardasil)

Quadrivalent HPV recombinant vaccine. First vaccine indicated to prevent cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal intraepithelial neoplasia grades 2 and 3) due to HPV types 6, 11, 16, and 18. Vaccine efficacy mediated by humoral immune responses following immunization series.

Adult

<26 years: 0.5 mL IM administered as 3 separate doses; administer second and third doses 2 and 6 mo after first dose, respectively
>26 years: Not established

Pediatric

<9 years: Not established
>9 years: Administer as in adults

Immunosuppressive therapies (eg, irradiation, antineoplastic agents, corticosteroids) may decrease immune response to vaccine

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Shake well before administering; administer in deltoid region of upper arm or in higher anterolateral thigh; individuals with impaired immune responsiveness (eg, HIV infection, neoplastic disease, currently taking immunosuppressive drugs) may not elicit antibody response; because of IM administration, do not administer to individuals with bleeding disorders (eg, thrombocytopenia, coagulation disorders, anticoagulant therapy); common adverse effects include pain, swelling, erythema, and/or pruritus at injection site and fever

Miscellaneous topical ointment

Kunecatechins is another FDA-approved topical product for genital warts.


Kunecatechins (Veregen)

Botanical drug product for topical use that consists of extract from green tea leaves. Mode of action unknown but does elicit antioxidant activity in vitro. Indicated for topical treatment of external genital and perianal warts (condylomata acuminatum) in immunocompetent patients.

Adult

Apply topically tid; use approximately a 0.5-cm strand of ointment topically for each external genital or perianal wart

Pediatric

<18 years: Not established

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

Not evaluated for urethral, intravaginal, cervical, rectal, or intra-anal HPV disease and should not be used to treat these conditions; avoid application to open wounds, eyes, and nose; wash hands before and after application; avoid sexual contact while ointment is on skin; may cause application-site reactions, phimosis, inguinal lymphadenitis, urethral meatal stenosis, dysuria, genital herpes simplex, vulvitis, hypersensitivity, pruritus, pyodermitis, skin ulcer, erosions in the urethral meatus, and superinfection of warts and ulcers

More on Papillomavirus

Overview: Papillomavirus
Differential Diagnoses & Workup: Papillomavirus
Treatment & Medication: Papillomavirus
Follow-up: Papillomavirus
Multimedia: Papillomavirus
References
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References

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  2. Beutner KR, Ferenczy A. Therapeutic approaches to genital warts. Am J Med. May 5 1997;102(5A):28-37. [Medline].

  3. Carr J, Gyorfi T. Human papillomavirus. Epidemiology, transmission, and pathogenesis. Clin Lab Med. Jun 2000;20(2):235-55. [Medline].

  4. Fazel N, Wilczynski S, Lowe L, Su LD. Clinical, histopathologic, and molecular aspects of cutaneous human papillomavirus infections. Dermatol Clin. Jul 1999;17(3):521-36, viii. [Medline].

  5. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. May 5 1997;102(5A):3-8. [Medline].

  6. Sedlacek TV. Advances in the diagnosis and treatment of human papillomavirus infections. Clin Obstet Gynecol. Jun 1999;42(2):206-20. [Medline].

  7. Tjalma WA, Arbyn M, Paavonen J, van Waes TR, Bogers JJ. Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer. Int J Gynecol Cancer. Sep-Oct 2004;14(5):751-61. [Medline].

  8. Wiley DJ, Douglas J, Beutner K, Cox T, Fife K, Moscicki AB, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. Oct 15 2002;35(Suppl 2):S210-24. [Medline].

  9. Siddiqui MA, Perry CM. Human papillomavirus quadrivalent (types 6, 11, 16, 18) recombinant vaccine (Gardasil). Drugs. 2006;66(9):1263-71; discussion 1272-3. [Medline].

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Further Reading

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Keywords

human papillomavirus, HPV, common warts, verruca vulgaris, palmo-plantar warts, flat warts, verruca plana, oral warts, focal epithelia hyperplasia, epidermodysplasia verruciformis, EDV, genital warts, condyloma acuminata, Bowen papulosis, Bowen disease, papillomas of the mucosal surfaces, intraepithelial neoplasias, papovavirus, sexually transmitted disease, STD, laryngeal papillomas, mosaic wart, butcher wart, extragenital Bowen disease, macular plaque, flat condylomata, cervical intraepithelial neoplasia, Buschke-Löwenstein tumor, vulvar intraepithelial neoplasia, cervical cancer, penile intraepithelial neoplasia, anal intraepithelial neoplasia, verrucae vulgaris, verrucae plana, Heck disease, flat condylomata, squamous intraepithelial neoplasia, giant condyloma, verrucous carcinoma, Bowenoid papulosis

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Contributor Information and Disclosures

Author

John D Shanley, MD, MPH, Professor Emeritus, University of Connecticut; Professor of Preventive Medicine, Stony Brook Medical Center
John D Shanley, MD, MPH is a member of the following medical societies: American Association for the Advancement of Science, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital Corporation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center
Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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