Management

In General

• No treatment may be an option, as about 30% of patients will experience spontaneous clearance of warts over a period of up to 6 months. However most patients seek treatment for the discomfort, anxiety, distress or the social unacceptability that warts cause.
• The objective of treatment is removal of visible warts. Eradication of HPV is not an achievable goal with current therapies and treatment has no measurable effect on transmission rates between partners.
• The evidence base to direct first and second line treatments is not strong
• All treatments have significant failure and relapse rates see Results of randomized controlled trials of therapies 
• Treatment may involve discomfort and local skin reactions
• Treatment choice depends on the patient preference as well as morphology, number, and distribution of warts
• Treatment decisions should be made after discussing the appropriate options with the patient
• Provision of written information on management of treatment side effects is recommended
• Very large wart lesions should be considered for surgical treatment
• Topical anaesthetics (eg lidocaine cream, EMLA®) can be used prior to cryotherapy particularly when treating larger lesions.
• Caution should be exercised using any modality of treatment because of the danger of oedema and necrosis of surrounding tissue.

Summary of the results of randomized controlled trials of therapies for anogenital warts among HIV negative patients (BASHH 2015)

Note

1. Clearance rates and recurrence rates are not directly comparable as clearance was measured at different times from the start of treatment and high loss to follow up was often experienced in the trials.
2. The `intention to treat` analysis of clearance rates provides a conservative estimate of efficacy. The number enrolled into each group was taken as the denominator and the number known to have cleared as the numerator.
   For any missing data, participants were assumed not to be cleared. For the `per protocol analysis, only those for whom follow-up data were available were included in the denominator and numerator; this may overestimate the efficacy.

Guidance for the initial management of external genital and peri-anal warts in men and non pregnant women is set out in the  Initial Management of External Genital and Peri-anal Warts in Men and Non Pregnant Women algorithm.

Important Considerations

• Latex condoms may be weakened by podophyllotoxin and imiquimod
• Clinicians should avoid the inadvertent exposure of pregnant women to podophyllotoxin and imiquimod which potentially may arise though the use of these products in a sexual partner. The area which is under treatment in a partner should be thoroughly washed before sexual contact occurs.
• GUM Consultants who are referred recalcitrant warts for review may consider additional therapeutic options such as trichloracetic acid
• Surgical excision or hyfrecation should be considered for warts which have failed to respond
• Biopsy may be necessary in some cases, eg, unusual appearance or failing to respond to treatment

Treatment Choice

In choosing between self-applied agents, podophyllotoxin and imiquimod appear broadly equivalent in safety
and efficacy. However its lower cost, shorter treatment duration and faster mode of action may make
podophyllotoxin preferred as a first choice. Sinecatechins have similar clearance rates in trials but no
randomised head-to-head comparisons with other treatments have been performed and the frequency of
dosing(three times daily) may be a barrier to adherence

Urethral meatus

• If the base of the lesions is seen, treatment with cryotherapy
• Lesions deeper in the urethra should be surgically ablated under direct vision, which may require referral to a urologist or the use of a meatoscope.

Refer to West of Scotland Pregnancy and STIs Guideline for the managment of Genital warts in pregnancy 

These may be refractory to treatment and should be discussed with a senior doctor from the outset.

Podophyllotoxin (WARTICON® and CONDYLINE® ) are purified extracts of podophyllin suitable for self administration

• Warticon® and Condyline® are licensed for the treatment of warts of the penis or the external female genitalia.
• Supervision by medical staff is recommended when the lesion area treated is greater than 4 cm²
• Warticon® and Condyline® are not licensed for use of extragential warts, however Warticon® is commonly used on external lesions at all sites
• Podophyllotoxin solution (0.5%) is preferred over the 0.15% cream formulation where it can be easily
  applied owing to slightly superior efficacy
• Condyline® is only available as a 0.5% alcoholic solution
• Treatment cycles consist of twice daily application for 3 days followed by 4 days rest for 4 cycles
• Warticon® and Condyline® should not be used in pregnancy and lactation
• It should not be used on broken skin
• Treatment should be discontinued if significant side effects (eg soreness, ulceration)
• Consider repeat cycles of treatment if the warts are responding although this is not licensed (see Initial Management of External Genital and Peri-anal Warts in Men and Non Pregnant Women)
• Unprotected sexual contact should be avoided soon after application because of a possible irritant effect on the partner

• Imiquimod (ALDARA®) is an immune response modifier
• It is licensed for external genital and peri-anal warts
• It should not be used in pregnancy and breast feeding
• It should be applied three times per week (example: Monday, Wednesday and Friday) and washed off 6 to 10 hours later
• It frequently causes local skin / mucous membrane irritation when applied for anogenital warts. This may be due to narrow therapeutic margin. Temporary halting of treatment may be required to manage side effects.
• Unprotected sexual contact should be avoided soon after application because of a possible irritant effect on the partner
• Use should continue until the clearance of visible genital or perianal warts or for a maximum of 16 weeks per episode of warts with 4 weekly reviews.
• Response to treatment may be delayed for some weeks. Extending treatment to 20 weeks or beyond in those who are showing a response is common practice but there is no trial evidence concerning this.
• Clinical trials of imiquimod versus placebo have shown response rates comparable with other topical agents.
• A lower relapse rate has been suggested, but clinical trials comparing relapse after other topical therapies have not been conducted.
• Normally used for refractory warts which have failed to respond to other treatments, or warts which have been assessed by a senior doctor/senior nurse and are thought likely to be refractory to treatment (eg extensive carpet warts). Some services may choose to use first line for keratinised lesions when cryotherapy is not an option.
• Immune deficiency may not be a contraindication for the use of imiquimod topically for anogenital warts and it has been used in HIV positive subjects but use in patients who are immunosuppressed should be discussed with a senior clinician.
• Has the potential to exacerbate inflammatory skin conditions; it should be used with caution in patients with autoimmune conditions although systemic absorption from topical treatment is likely to be negligible.

• Cryotherapy is the name given to treatments which involve liquid nitrogen spray freezing the skin, causing cytolysis (cell breakdown) resulting in necrosis
• Suitable for a small number of lesions
• Success partly depends on ability to treat at regular (normally weekly) intervals. Services report high rates of non attendance for appointments. These factors should be taken into account when deciding whether home treatment with topical agents may be preferable.
• Treatment of choice in pregnancy and intrameatal warts
• Treatment should be applied until a halo of freezing has been established a few millimetres round the treated lesion. A freeze, thaw, freeze technique should be used.
• Response rates depend on size and chronicity of the lesions
• Usually repeated at weekly intervals; lack of response after four weeks should prompt consideration of an alternative treatment modality.
• Liquid nitrogen is a hazardous substance which requires great care during handling. Only health professionals who have received appropriate training may administer cryotherapy.
• Caution: The storage and handling of liquid nitrogen should be undertaken according to health and safety guidance (see British Oxygen British Oxygen, COSHH Essentials  and the Health & Safety Executive