Approach

Given the benign course of genital warts and the potential for them to resolve spontaneously, treatment is not always indicated.[3][43] Once the patient and physician determine that treatment is required, then the method of treatment may be based on both patient and physician preference.

Factors that play a role in deciding on a treatment modality include: location of the wart(s), the extent of surface area affected, wart morphology, response to previous treatments, the desire for self-administration versus physician-administration, treatment cost, adverse effects, co-existing medical conditions, and provider experience.​[7][43] A course of therapy rather than a single treatment is usually indicated.[6]​​[43] 

In general, the goal of treatment is to destroy or remove visible lesions. Although treatment may reduce human papillomavirus (HPV) infectivity, it is unlikely to eradicate it.[6]​​[43] No evidence exists showing that treatment decreases the rate of sexual transmission of HPV.[3][43]

Immunocompetent patients

A variety of treatments exist without the identification of a clear first-line treatment. No single agent is ideal for all patients or all warts. Treatment must be guided by a number of factors as mentioned above. If a patient does not improve significantly after 3 provider-administered treatments, or does not achieve complete clearance of lesions after 6 treatments, then an alternate therapy should be used.[6]​​​[7]

Topical agents including podophyllotoxin and imiquimod cream have been used as patient-administered treatments for genital warts with variable efficacy. [ Cochrane Clinical Answers logo ] These agents are applied in the privacy of the patient's home. The frequency and duration of use varies depending on the specific agent. Patient compliance with self-administered treatments can be of concern and should be considered as a possible cause for lack of response to a particular therapy.

Patient-applied therapy

  • Podophyllotoxin works by arresting cell division in mitosis, by binding subunits of microtubules.[7]​ Patients may find it difficult to restrict application of podophyllotoxin topical solution to the genital warts. Podophyllotoxin gel is easier for patients to apply, and it has been shown to have the same efficacy and rates of recurrence as the topical solution.[47] Local inflammation, burning, itching, and pain are common side effects.[3]

  • Imiquimod is a topical immune modulator that induces the production of the cytokines interferon alfa, interleukin-6 (IL-6), IL-8, and tumour necrosis factor-alpha (TNFa), among others, leading to a T-cell-mediated, cytotoxic immune response.[7]​ Studies have shown that treatment with imiquimod leads to significant wart clearance compared with placebo. Recurrence rates are relatively low when compared with other treatments, such as podophyllotoxin.[13] Side effects include localised pruritus, erythema, erosion, burning, and pain.[4] Non-scarring healing is considered to be one of the advantages of this treatment. However, use of imiquimod is sometimes limited by cost. An application schedule of 3 times per week for imiquimod 5% cream for external anogenital warts has been found to be the optimal schedule.[48]

  • Sinecatechins ointment, also known as Polyphenon E, is a standardised extract of green tea, which has immunostimulatory, antiproliferative, and antitumour properties. The exact mechanism of action is not fully understood.[49][50][51] Studies have shown complete clearance rates up to 57.2%. Common side effects include local erythema, pruritus, irritation, and pain.[52]

Provider-administered therapy

  • Cryotherapy destroys warts by thermal-induced cytolysis. Studies suggest that it is effective, with few adverse effects.[53] Cryotherapy can be quite painful and generally requires multiple treatments.

  • Trichloroacetic acid (TCA) and bichloroacetic acid (BCA) are caustic agents that destroy warts by chemical coagulation. They can be used to treat small, moist genital warts. Recurrence rates are high.[54] These agents have significant cytodestructive potential and therefore must be applied by a healthcare provider to prevent contact with normal skin and mucous membranes.[13][43]

  • Surgical excision eliminates warts in a single visit. It can be used in patients with limited, average, or extensive wart involvement.[6]​ Surgical excision may serve as a precursor to other treatments in extensive cases by debulking widely involved areas.[6]​ Methods include tangential scissor excision, shave excision, curettage, and electrosurgery.

  • Alternative therapies include CO₂ laser ablation and electrodessication. These also render a patient free of warts within 1 visit. These more invasive techniques are useful for patients with a large area of wart involvement.

  • Photodynamic therapy (PDT) with topical or intra-lesional aminolevulinic acid (a photosensitising agent) is a specialised form of photochemotherapy that has been shown to be effective in treating external genital warts.[55] Once applied, aminolevulinic acid is absorbed by rapidly proliferating cells infected with HPV. Activation of aminolevulinic acid by light exposure and in the presence of oxygen leads to the formation of singlet oxygen, which causes oxidative damage and destruction of the genital warts. This is an off-label use of PDT.

Immunocompromised patients

Genital warts in immunocompromised patients can be resistant to standard treatment, and recurrences are more likely. Treatment in this population is important, as the likelihood of spontaneous resolution is less likely and there is an increased risk of transformation into squamous cell carcinoma.[20][56]​ A longer duration of treatment or a combination of therapies may need to be implemented.[57][58]​​ Clinical assessment of the lesions over time will determine the course and aggressiveness of treatment.

Surgical excision followed by non-invasive therapies may be indicated. Other combination therapies may also be employed.[58]​​[59]​​ Relapse rates of condyloma in the HIV-infected population have been found to decrease with improvement of the underlying HIV infection through use of antiretrovirals.[60]

One randomised, double-blind, placebo-controlled study showed that topically applied imiquimod 5% cream reduced wart area and may have clinical utility in treating external genital warts in HIV-infected individuals. However, the clearance rate of those treated with imiquimod did not differ significantly from the rate for the placebo group.[61] Further studies are required to determine the most appropriate treatment approach for this patient population.

Recommended regimens for external warts

  • Patient-applied topical agents:[43]

    • Podophyllotoxin. The predecessor to podophyllotoxin, podophyllum, is not routinely used as it contains mutagens.[62]

    • Imiquimod.[48]

    • Sinecatechins.[49]

  • Provider-administered:[43]

    • Cryotherapy with liquid nitrogen or cryoprobe.

    • TCA or BCA 80% to 90% solution: small amount is applied on warts and allowed to dry; a 'frosting' develops. Treatment can be repeated weekly.

    • Surgical removal: can be tangential scissor excision, shave excision, curettage, or electrosurgery.

    • Laser surgery.

Recommended regimens for internal warts

Vaginal warts or intra-anal warts:[43]

  • Cryotherapy with liquid nitrogen

  • Surgical removal

  • TCA or BCA 80% to 90% solution.

Urethral meatus warts:[43]

  • Cryotherapy

  • Surgical removal.

Pregnant women

Genital warts may proliferate and become easily irritated during pregnancy. Although the warts can be removed, they may not resolve fully until the pregnancy is over.[43] Removal methods include cryotherapy, surgery, or laser; TCA or BCA can also be used, but these are the most effective for moist warts.​[6]

Podophyllotoxin must be avoided as it is teratogenic. Imiquimod and sinecatechins have not been adequately studied in pregnant patients for use in genital warts and thus should be avoided.

HPV types 6 and 11 have been associated with laryngeal papillomatosis in infants. However, the presence of genital warts is not an indication for caesarean delivery.[63] A caesarean section is indicated only in the rare circumstance of obstruction or bleeding.[43]

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