Human Papillomavirus Medication
- Author: Peter A Gearhart, MD; Chief Editor: Burke A Cunha, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The medications used to treat human papillomavirus (HPV) infections are primarily designed to ablate the lesion by virtue of their corrosive properties. Although medical treatments have historically been destructive, immunomodulatory agents have now been introduced into practice.
Keratolytic agents like TCA and bichloracetic acid (BCA) are extremely powerful keratolytic agents that rapidly penetrate and chemically cauterize skin, keratin, and other tissues. They can be used to treat nongenital cutaneous warts, as well as external genital warts (EGWs) or condylomata acuminata.
For most patients, simple topical therapies are the initial treatments of choice; they are cost effective and result in minimal toxicity. Most such therapies successfully eliminate visible condylomata in 30-90% of cases. However, many clinical studies examining topical therapies are not well designed, making comparisons between therapies difficult.
Immunomodulators
Class Summary
Immune response modifiers have immunomodulatory effects and are used for treatment of external anogenital warts (EGWs) or condylomata acuminata. Interferon alfa, beta, and gamma may be administered topically, systemically, and intralesionally. They stimulate production of cytokines and demonstrate strong antiviral activity.
Imiquimod (Aldara, Zyclara)
Imiquimod is an imidazoquinolinamine derivative that has no in vitro antiviral activity but does induce macrophages to secrete cytokines such as interleukin (IL)-2 and interferon alfa and gamma. Its mechanisms of action are unknown. Imiquimod has been studied extensively and is a new therapy relative to other EGW treatments. It may be more effective in women than in men.
Imiquimod is dispensed as an individual dose. Patients are advised to wash the affected area with mild soap and water upon awakening and to remove residual drug.
Interferon alfa-n3 (Alferon N)
Interferon alfa is a protein product either manufactured from a single-species recombinant DNA process or obtained from pooled units of donated human leukocytes that have been induced by incomplete infection with a murine virus.
The mechanisms by which interferon alfa exerts antiviral activity are not understood clearly. However, modulation of the host immune response may play an important role. This agent is indicated for intralesional treatment of refractory or recurring external condyloma acuminatum and is particularly useful for patients who have not responded satisfactorily to other treatment modalities (eg, podophyllin, surgical excision, laser therapy, or cryotherapy).
Interferon alfa-2b (Intron A)
This is a protein product manufactured by recombinant DNA technology. Its mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. Its immunomodulatory effects include suppression of tumor cell proliferation, enhancement of macrophage phagocytic activity, and augmentation of lymphocyte cytotoxicity.
This agent is indicated for intralesional treatment of refractory or recurring external condyloma acuminatum and is particularly useful for patients who have not responded satisfactorily to other treatment modalities (eg, podophyllin, surgical excision, laser therapy, or cryotherapy).
Keratolytic Agents
Class Summary
Antimitotic drugs arrest dividing cells in mitosis, resulting in the death of proliferating cells. They cause cornified epithelium to swell, soften, macerate, and then desquamate. Many of them are chemotherapeutic agents. The drugs listed below are used specifically for treatment of EGWs or condylomata acuminata.
Keratolytic agents are used to aid in removal of keratin in hyperkeratotic skin disorders, including corns, ichthyoses, common warts, flat warts, and other benign verrucae.
Podofilox (Condylox)
Podofilox is a topical antimitotic that can be synthesized chemically or purified from the plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum). It is the active agent of podophyllin resin and is available as a 0.5% solution. Treatment results in necrosis of visible wart tissue; the exact mechanism of action is unknown. Treatment should be limited to no more than 10 cm2 of wart tissue, and no more than 0.5 mL/day of solution should be given. This is a patient-applied therapy.
Podophyllum resin (Podocon-25)
Podophyllin is derived from May apple (Podophyllum peltatum Linné) and contains the active agent podophyllotoxin, a cytotoxic substance that arrests mitosis in metaphase. American podophyllum contains one fourth the amount of podophyllotoxin that Indian podophyllum does. The potency of podophyllin varies considerably between batches. The exact mechanism of action is unknown.
Podophyllin is used as a topical treatment for benign growths, including external genital and perianal warts, papillomas, and fibroids. It results in necrosis when applied to anogenital warts. Only a trained medical professional can apply it, and it cannot be dispensed to a patient.
Trichloroacetic acid 85% (Tri-Chlor)
Trichloroacetic acid (TCA) is a highly corrosive desiccating agent that cauterizes skin, keratin, and other tissues and is used to burn lesions. Although it is caustic, it causes less local irritation and systemic toxicity than other agents in the same class. However, response often is incomplete, and recurrence is common.
Most clinicians use 25-50% TCA, although some use concentrations as high as 85% and then neutralize with either water or bicarbonate. Tissue sloughs and subsequently heals in 7-10 days. TCA therapy is less destructive than laser surgery, electrocautery, or cryotherapy.
Salicylic acid (Compound W, Dr. Scholl's Clear Away Warts, Freezone)
By dissolving the intercellular cement substance, salicylic acid produces desquamation of the horny layer of skin without affecting the structure of viable epidermis. It is used for removal of nongenital cutaneous warts, particularly common or plantar warts. Before application, wash the affected area. The wart may be soaked in warm water for 5 minutes. Dry the area thoroughly.
Antineoplastics, Antimetabolite
Class Summary
Antimetabolites interfere with nucleic acid synthesis and inhibit cell growth and proliferation. These are topical preparations that contain the fluorinated pyrimidine 5-fluorouracil (5-FU). Although these chemotherapeutic agents are not formally approved for use against warts, some studies have demonstrated a benefit against EGWs or condylomata acuminata.
Fluorouracil topical (Efudex, Carac, Fluoroplex)
Topical 5-FU interferes with DNA synthesis by blocking the methylation of deoxyuridylic acid and inhibits thymidylate synthetase, which subsequently reduces cell proliferation. Its primary indication is for topical treatment of actinic keratoses. Although it is not approved by the US Food and Drug Administration (FDA) for the treatment of warts, it has been used in adults, particularly for warts resistant to other forms of treatment. It is used for management of superficial basal cell carcinomas.
The solution contains either 2% or 5% 5-FU in propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, paraben, and disodium edetate. The cream contains 5% 5-FU in white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60, and paraben. When topical 5-FU is applied to the lesion, the area undergoes a sequence of erythema, vesiculation, desquamation, erosion, and reepithelialization.
Vaccines, Inactivated, Viral
Class Summary
Two vaccines are now available for the prevention of HPV-associated dysplasias and neoplasia, including cervical cancer, genital warts (condylomata acuminata), and precancerous genital lesions. Girls and young women aged 9-26 years should receive the complete immunization series.
The quadrivalent vaccine is also indicated for routine use in males aged 11 or 12 years. Current recommendations advise vaccination for males aged 13 through 21 years who have not been vaccinated previously or who have not completed the 3-dose series. Males aged 22 through 26 years may be vaccinated as well.
Papillomavirus vaccine, quadrivalent (Gardasil)
The quadrivalent HPV recombinant vaccine was the first vaccine indicated to prevent cervical cancer, genital warts (condylomata acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades I-III; vulvar intraepithelial neoplasia grades II and III; and vaginal intraepithelial neoplasia grades II and III) due to HPV types 6, 11, 16, and 18. Its efficacy is mediated by humoral immune responses following immunization series.
The quadrivalent vaccine is FDA-approved for females aged 9-26 years and is under FDA priority review to evaluate efficacy in women aged 27-45 years. It is indicated for boys and men aged 11-26 years for prevention of condylomata acuminata caused by HPV types 6 and 11. It is also indicated in people aged 9-26 years for prevention of anal cancer and associated precancerous lesions.
Papillomavirus vaccine, bivalent (Cervarix)
The bivalent HPV vaccine is a recombinant vaccine prepared from the L1 protein of HPV types 16 and 18. It is indicated in girls and women aged 10-25 years for the prevention of diseases caused by oncogenic HPV types 16 and 18 (eg, cervical cancer, cervical intraepithelial neoplasia grade II or higher, adenocarcinoma in situ, and cervical intraepithelial neoplasia grade I).
Topical Skin Products
Class Summary
Sinecatechins is another topical product that has gained FDA approval for genital warts.
Sinecatechins (Veregen)
Sinecatechins ointment is a botanical drug product for topical use that consists of extract from green tea leaves. It contains 15% sinecatechins and is available in 15- and 30-g tubes. Its mode of action is unknown, but it does elicit antioxidant activity in vitro. Sinecatechins ointment is indicated for topical treatment of external genital and perianal warts (condylomata acuminata) in immunocompetent patients.
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| Nongenital Cutaneous Disease | HPV Type |
| Common warts (verrucae vulgaris) | 1, 2, 4, 26, 27, 29, 41, 57, 65, 75-78 |
| Plantar warts (myrmecias) | 1, 2, 4, 60, 63 |
| Flat warts (verrucae planae) | 3, 10, 27, 28, 38, 41, 49 |
| Butcher’s warts (common warts of people who handle meat, poultry, and fish) | 1-4, 7, 10, 28 |
| Mosaic warts | 2, 27, 57 |
| Ungual squamous cell carcinoma | 16 |
| Epidermodysplasia verruciformis (benign) | 2, 3, 10, 12, 15, 19, 36, 46, 47, 50 |
| Epidermodysplasia verruciformis (malignant or benign) | 5, 8-10, 14, 17, 20-25, 37, 38 |
| Nonwarty skin lesions | 37, 38 |
| Nongenital Mucosal Disease | HPV Type |
| Respiratory papillomatosis | 6, 11 |
| Squamous cell carcinoma of the lung | 6, 11, 16, 18 |
| Laryngeal papilloma (recurrent respiratory papillomatosis)[14] | 2, 6, 11, 16, 30, 40, 57 |
| Laryngeal carcinoma | 6, 11 |
| Maxillary sinus papilloma | 57 |
| Squamous cell carcinoma of the sinuses | 16, 18 |
| Conjunctival papillomas | 6, 11 |
| Conjunctival carcinoma | 16 |
| Oral focal epithelial hyperplasia (Heck disease) | 13, 32 |
| Oral carcinoma | 16, 18 |
| Oral leukoplakia | 16, 18 |
| Squamous cell carcinoma of the esophagus | 16, 18 |
| Anogenital Disease | HPV Type |
| Condylomata acuminata | 1-6, 10, 11, 16, 18, 30, 31, 33, 35, 39-45, 51-59, 70, 83 |
| Bowenoid papulosis | 16, 18, 34, 39, 40, 42, 45 |
| Bowen disease | 16, 18, 31, 34 |
| Giant condylomata (Buschke-Löwenstein tumors) | 6, 11, 57, 72, 73 |
| Unspecified intraepithelial neoplasia | 30, 34, 39, 40, 53, 57, 59, 61, 62, 64, 66-69 |
| Low-grade squamous intraepithelial lesions (LGSIL) | 6, 11, 16, 18, 26, 27, 30, 31, 33-35, 40, 42-45, 51-58, 61, 62, 67-69, 71-74, 79, 81-84 |
| High-grade squamous intraepithelial lesions (HGSIL) | 6, 11, 16, 18, 31, 33, 35, 39, 42, 44, 45, 51, 52, 56, 58, 59, 61, 64, 66, 68, 82 |
| Carcinoma of vulva | 6, 11, 16, 18 |
| Carcinoma of vagina | 16 |
| Carcinoma of cervix[15, 16] | 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, 82 |
| Carcinoma of anus | 16, 31, 32, 33 |
| Carcinoma in situ of penis (erythroplasia of Queyrat) | 16 |
| Carcinoma of penis | 16, 18 |
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