Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

non-pregnant and immunocompetent

1st line – patient-applied therapy

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ONGOING
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non-pregnant and immunocompetent
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external genital warts
1st line – 

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

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 were 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]

Primary options

podophyllotoxin topical: (0.5%) apply to the affected area(s) twice daily for 3 days, followed by 4 days of no treatment, may repeat for up to 4 cycles

OR

imiquimod topical: (5%) apply to the affected area(s) three times weekly at bedtime for up to 16 weeks, leave for 6-10 hours before washing off; (3.75%) apply to the affected area(s) once daily at bedtime for up to 8 weeks, leave for 8 hours before washing off

OR

sinecatechins: (15%) apply to the affected area(s) three times daily for up to 16 weeks

1st line – provider-administered therapy

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ONGOING
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non-pregnant and immunocompetent
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external genital warts
1st line – 

provider-administered therapy

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

Trichloroacetic acid and bichloroacetic acid are caustic agents that destroy warts by chemical coagulation. They can be used to treat small, moist genital warts.[6]​ 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] If an excess of acid is applied, the area should be powdered with talc, sodium bicarbonate, or liquid soda.

Surgical excision removes warts promptly, providing a wart-free state. 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 more invasive techniques are useful for patients with a large area of wart involvement. They render a patient free of warts within 1 visit.

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 human papillomavirus. 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.

1st line – cryotherapy with liquid nitrogen

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ONGOING
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non-pregnant and immunocompetent
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vaginal warts or intra-anal warts
1st line – 

cryotherapy with liquid nitrogen

Destroys warts by thermal-induced cytolysis.

Can be quite painful and generally requires multiple treatments.

1st line – surgical removal

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ONGOING
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non-pregnant and immunocompetent
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vaginal warts or intra-anal warts
1st line – 

surgical removal

Removes warts promptly, providing a wart-free state. 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]

1st line – trichloroacetic acid or bichloroacetic acid

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ONGOING
|
non-pregnant and immunocompetent
|
vaginal warts or intra-anal warts
1st line – 

trichloroacetic acid or bichloroacetic acid

Trichloroacetic acid and bichloroacetic acid 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] If an excess of acid is applied, the area should be powdered with talc, sodium bicarbonate, or liquid soda.

1st line – cryotherapy with liquid nitrogen

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ONGOING
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non-pregnant and immunocompetent
|
urethral meatus warts
1st line – 

cryotherapy with liquid nitrogen

Destroys warts by thermal-induced cytolysis. Studies suggest that it is effective, with few adverse effects.[53]

Can be quite painful and generally requires multiple treatments.

1st line – surgical removal

Back
ONGOING
|
non-pregnant and immunocompetent
|
urethral meatus warts
1st line – 

surgical removal

Removes warts promptly, providing a wart-free state. 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]

immunocompromised

1st line – combination therapy and/or longer therapy

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ONGOING
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immunocompromised
1st line – 

combination therapy and/or longer therapy

Genital warts in immunocompromised patients can be resistant to standard treatment, and recurrences are more likely. 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]

pregnant

1st line – destructive therapies or trichloroacetic acid or bichloroacetic acid

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ONGOING
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pregnant
1st line – 

destructive therapies or trichloroacetic acid or bichloroacetic acid

Genital warts may be removed with destructive methods, including cryotherapy, surgery, or laser.​[6]

Trichloroacetic acid or bichloroacetic acid can also be used, but are most effective for moist warts.[6]​ These caustic agents destroy warts by chemical coagulation. They have significant cytodestructive potential and therefore must be applied by a healthcare provider to prevent contact with normal skin and mucous membranes.[13] If an excess of acid is applied, the area should be powdered with talc, sodium bicarbonate, or liquid soda.

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.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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