Patients should receive a comprehensive explanation of their condition to include information on the natural history, transmission and treatment of warts. This should be reinforced with up-to-date written advice (see BASHH Patient Information Leaflet)
AGW treatments include self-applied (topical) agents and clinician-applied therapies (topical or ablative). The choice of treatment depends on treatment availability, patient preference, volume and location of lesions and the patient’s prior experience of and response to treatment. There is no single best treatment for warts and direct comparisons of clearance and recurrence rates between trials are problematic due to differences in study populations and protocols.
The development of a local treatment algorithm has been shown to improve patient outcomes and is recommended, based on local availability of treatment options.
Patient-applied treatments
Imiquimod (1A)
Imiquimod is an immune response modifier which acts via induction of alpha-interferon and other cytokines.
In the UK it is available as a 5% cream preparation (Aldara®) supplied in sachets, each containing sufficient cream to cover 20 cm2 wart area. The cream should be applied three times weekly in a thin layer directly to wart tissue prior to normal sleeping hours and
washed off after 6–10 h. Local skin reactions, most commonly erythema, excoriation and erosion, occur 70%–80% of treated individuals and correlate with clinical response. Treatment should be applied until disappearance of warts for a maximum of 16 weeks. It has the potential to exacerbate inflammatory skin conditions and should be used with caution in solid organ transplant recipients and in individuals with autoimmune
conditions.
Recommendations:
We suggest that where individuals have a <50% reduction in wart volume after 8 weeks’ of imiquimod, a switch to an alternative treatment should be considered (2B)
Podophyllotoxin (1A)
Podophyllotoxin is an anti-mitotic agent which arrests mitosis in metaphase leading to epithelial cell death of virally infected cells. It is available as 0.5% solution or 0.15% cream which should be applied twice daily directly to lesions on three consecutive days, repeated weekly for a maximum of 4 weeks. Recent RCT evidence suggests it can be continued beyond this licensed duration to achieve maximal wart clearance. Although it is not licensed for use on perianal lesions, RCT evidence suggests podophyllotoxin is safe and effective at this site. The cream preparation is preferable for ease of application at perianal and other difficult to reach sites although has been shown to have slightly inferior efficacy to solution for initial clearance of warts. Local skin reactions are common and it may be caustic to normal skin.
Recommendations:
We suggest that podophyllotoxin solution should be preferred over the cream formulation at easy to reach sites owing to slightly superior efficacy for initial wart clearance (2A)
We recommend that podophyllotoxin 0.15% cream may be used for the treatment of external perianal warts on an off-license basis (1B)
Sinecatechins (1A)
Sinecatechins is the extract of Camellia sinensis (green tea) plant and contains the active ingredient epigallocatechingallate. Its mechanism of action is not fully known. It is available in the UK as a 10% ointment (Catephen®) which is applied directly to warts three times daily until clearance, for a maximum duration of 16 weeks.
It is not necessary to wash the ointment off the affected area prior to the next application. Mild inflammatory reactions are common following application and correlate with clinical response.
Recommendations: We suggest that where individuals have a <50% reduction in wart volume after 8 weeks’ of sinecatechins, switch to an alternative treatment should be considered (2B)
Clinician-applied treatments
Cryotherapy (1A)
Cryotherapy destroys warts by thermal induced cytolysis and is usually available as a liquid nitrogen open spray or, less commonly, closed systems with a cryoprobe opposed directly against the lesion using nitrous oxide or CO2 cylinders. Portable canisters with alternative compressed gas formulations (Norfluorane/Dimethyl ether/propane) have become available more recently. These offer advantages over standard cryotherapy systems in their storage and maintenance, however no safety or efficacy data are yet available to support their use for AGW treatment.
Multiple treatment sessions may be required to achieve wart clearance. Systematic studies on the optimal frequency and application technique for cryotherapy are lacking although retrospective data suggest weekly treatment may reduce the total number of applications required versus longer intervals. Local anaesthetic is not usually required although individuals may experience localised pain, blistering, pigment change or scarring following treatment.
Recommendations: We recommend that cryotherapy is given weekly with one or two freeze-thaw cycles performed per treatment session (1B)
A recommended freeze-thaw cycle should involve cautious application of the cryo-spray in brief bursts to achieve visible freezing of the lesion(s) and 1 mm surrounding halo for up to 20 s followed by visible thawing (1B)
Laser (1A)
Laser therapy destroys warts by inducing vascular thrombosis in dermal papillary vessels leading to destruction of keratinocytes. Destruction of the blood vessels results in release of pro-inflammatory cytokines that enhances the cellular immune response which may aid in eradication of HPV. In addition, ablative laser therapy uses
longer wavelength laser that is absorbed by water and vaporises keratinocytes.
Four modalities of laser therapy are used for treatment of warts:
(1) Pulsed dye
(2) Neodymium-doped yttrium aluminum garnet (Nd:YAG)
(3) Carbon dioxide (CO2)
(4) Erbium-doped yttrium aluminum garnet (Er:YAG)
Pulsed dye and Nd:YAG lasers are non-ablative lasers which may be less effective for pigmented lesions and individuals with darker skin. CO2 and Er:YAG are ablative lasers.
Although comparative studies with other wart treatments are limited, evidence from systematic reviews and network meta-analyses suggest higher clearance rates than standard topical treatments or cryotherapy albeit at higher cost.
Recommendations:
We recommend that local anaesthetic is administered prior to laser treatment for AGW (1B)
We recommend that exhaust ventilation and PPE including N95 or FFP2/3 particulate respirator are employed during laser treatment of AGW (1A)
For other clinician-applied treatments (e.g. electrosurgery, TCA, 5-FU) please review the full guideline.
Warts at internal anatomical sites
Management of internal urethral, cervical, vaginal or anal warts may be challenging as they are often less accessible for clinical evaluation and the application/delivery of local treatments. Moreover, as individuals with internal warts are
often excluded from clinical trials, the evidence base for treatments is largely limited to observational studies or case series. Internal warts may be of less cosmetic concern therefore deferral of treatment is an option for asymptomatic lesions. Nonetheless as visualisation of such lesions may be difficult, clinicians should have a low threshold for biopsy where there is any diagnostic uncertainty.
We recommend the following treatments for cervical warts: surgical excision, laser, electrosurgery, cryotherapy or TCAA (1A)
We recommend colposcopy examination of all suspected HPV-related cervical lesions to differentiate between lowgrade and high-grade lesions (1C)
We recommend the following treatments for anal warts: surgical excision, laser, electrosurgery, cryotherapy, TCAA or imiquimod (1B)
Follow-up
Routine follow-up is not required for individuals whose warts have resolved. Follow-up should be arranged for individuals with warts still present at the end of treatment, or at 8 weeks following treatment initiation with imiquimod or sinecatechins.