Treatment

THERAPIES FOR TREATMENT OF WARTS, LSIL, HSIL

Office-based Therapies:

1. Trichloracetic acid (TCA) 80-90% Solution. This is an acid that works by destroying the wart on contact. It is applied to the wart with a cotton tip applicator. Very small lesions can be treated using the wooden tip of the applicator. The surrounding skin should be covered with a barrier cream or gel to protect healthy skin from any spills or drips. TCA will burn with the initial application but discomfort is usually short-term. It will cause a burning sensation, and the wart will eventually fall off, sometimes leaving an ulceration. TCA can be used for internal or external warts. It usually requires several treatments. External warts can be treated weekly but internally warts should be treated 2-3 weeks apart in order to allow healing of the anal mucosa. If a wart is not successfully treated by the fourth application, an alternative method should be found. Thick, large lesions may be difficult to treat with TCA because the acid may not penetrate to treat the entire wart. A similar agent, bichloracetic acid or BCA, is also used.

   Indications: Internal or external, warts, LSIL and HSIL, limited disease.

2. Cryotherapy. External warts can also be treated by freezing with liquid nitrogen, nitrous oxide, or carbon dioxide. Liquid nitrogen is applied by spraying or direct contact with a swab; nitrous oxide is connected to a closed cryo-system and applied with a probe to produce an iceball. The freezing causes necrosis of the wart. This may also cause mild irritation, and may be uncomfortable during the process. Discomfort can be reduced by applying lidocaine spray or gel prior to freezing. Cryotherapy causes the wart to fall off within a few days and may leave a shallow ulceration, which generally heals without scarring. It may require several applications. These treatments can be 1-2 weeks apart. Like TCA, the lesion must be completely treated. If the warts have not been successfully treated by the fourth application, an alternative method should be sought.

   Indications: External warts, LSIL or HSIL. Limited disease. Safe during pregnancy.

   A combination of cryotherapy and TCA can sometimes produce more rapid clearance of the warts. However, the double application can cause more severe discomfort than either alone.

3. Podophyllin is an extract from the podophyllum plant. It can be prepared as a 10% - 25% tincture. It causes the warts to erode approximately 3-5 days after treatment. It is applied to the external warts and must be washed off four hours later. There are several problems associated with podophyllin including low efficacy, potential for toxicity and it may be carcinogenic. It is therefore no longer recommended and is seldom used any more1.

   Indications: External warts; should not exceed 3-4 treatments. Should not be used in pregnancy.

4. Electrocautery. Lesions can be treated by application of an electric needle to cauterize or burn the warts. Local anesthesia should be used. Small lesions can be treated in a clinic setting, but larger and more extensive lesions usually require treatment in an outpatient surgery setting (see Surgery). The cauterization destroys the warts or lesions. Bleeding and discomfort following the procedure is common and can last for several days or weeks depending on the extent of treatment. However, the warts and lesions are more completely treated in one application and generally do not require multiple treatments. Even so, warts may recur with electrocautery as with any treatment modality.

   Indications: Internal or external warts, LSIL, HSIL. Safe during pregnancy. Office procedure limited to the tolerance of the patient; more extensive than TCA, less extensive than outpatient surgery.

5. Infrared Coagulation (IRC): IRC was developed for the treatment of external anal warts, hemorrhoids and tattoo removals. More recently it has been shown to be an effective treatment for internal anal HSIL and warts2. The treatment involves the application of a heat-guided probe directly to the lesions. The heat is at a lower range than laser or cauterization. It does not burn the lesions but rather destroys the tissue, similar to a sunburn blister, which can than be removed. It can be done as an office therapy with minimal discomfort both during and after the procedure. Patients are anesthetized pre-treatment with lidocaine gel followed by the injection of 1% lidocaine into the areas to be treated. The treatment can take up to an hour but post-treatment recovery is brief and there are none of the risks of surgical intervention. Following treatment there is frequently bleeding with bowel movements for up to 2-3 weeks. Post-procedure pain may require medication for 1-3 days but for most patients it is minimal although noticeable. The pain can be minimized by frequent soaking in hot water, especially following bowel movements. Care should be taken to increase fluids at this time to avoid constipation. Although the procedure takes longer than the application of TCA, the lesions are usually completely treated in one procedure. Extensive disease may require an additional treatment. We generally schedule a follow up exam two months following the procedure. If there was too much to treat in one session, we complete the treatment at the next visit.

   Indications: Internal and external LSIL and HSIL; Can effectively treat more extensive areas (50-70%) but may require 2 treatments if extensive.

6. Laser Therapy: Clinicians trained in laser therapy can apply this technique for perianal disease as well. There are also case reports of laser therapy for intra-anal lesions and it has become a more common practice in some offices. It appeared to be effective in some studies3-5, but there were significant recurrences of the group treated with laser in another study6. More extensive treatments, or those done in conjunction with ablation of cervical, vaginal or vulvar warts, are often done in an operating room. It is done in conjunction with the colposcope for guidance in finding the areas to treat. Laser treats the HPV by destroying it with heat. The laser controls the depth of treatment, which can help minimize scarring. Extensive treatments can be painful and can be managed with hydrocodone/acetaminophen. The pain may be minimal for the first few days since the nerve endings may be burnt initially, but can last for 2-3 weeks. Soaking in warm water especially following bowel movements will be soothing and can facilitate healing. It can take up to two months for the area to heal completely.

   Indications: Warts, LSIL or HSIL, more commonly used for external disease but internal disease can be treated as well.

Patient-applied therapies

1. Aldara™ (5% imiquimod cream). This is an immune response modulating treatment, which acts to produce a local interferon response. This stimulates the immune system to recruit immune cells to the area and causes the warts to regress. It is applied to the warts and rubbed in 3x/weekly at bedtime and rinsed off in the morning. The treatment continues for 12-16 weeks. Local irritation is expected and is a sign that the treatment is working. It can take 3-4 weeks for the treatment to start working. Occasionally the reaction is severe and the cream should be stopped until the inflammation goes away, or reduced to twice weekly. It is sometimes used post-operatively to prevent recurrence of warts. Or it is used continuously once the warts are clear, prophylactically 2x/ week. It has been used experimentally intra-anally7. One study showed it reduced recurrences of anal warts following surgery8 and was also effective as a primary treatment for anal HSIL9.

Indications: External anal warts, especially primary outbreaks. The patient must be able to adequately reach the affected areas. Patients should be shown how to apply the cream correctly in the office. Safety in pregnancy is not established. Safety for internal disease is not established.

2. Condylox™ (.15% podophyllotoxin cream) or Podofilox™ (.5% podophyllotoxin gel, solution, or cream). These are purified extracts of the podophyllum plant. They are applied twice daily for three consecutive days, followed by 4-7 days without treatment. The treatment can be repeated for 4 cycles. Warts that have not responded after 4 treatments should be treated with an alternative treatment. The treatment can cause burning, tenderness, and swelling and the warts will erode after a few days.

   Indications: External anal warts. Should not be used in pregnancy.

3. Efudex™ 5% fluorouracil cream has been suggested for treatment of anal warts but has not been studied. It is occasionally used for treatment of anal warts that are confluent with vulvar warts, and when all other therapies have failed. For a therapy that has been available for several decades it is surprising how little research has been published regarding its efficacy. Several studies reported its use alone or adjunctively in the treatment of intra-urethral, penile, and vulvar warts10, 11. It was effective in treatment of women with extensive vulvar condyloma in two randomized studies evaluating different treatment regimens12, 13. Several small studies of women with vaginal or vulvar intraepithelial neoplasia showed efficacy rates of 41% to 91%12, 14-16. It was also shown to prevent recurrence of cervical SIL in HIV-seropositive woman following laser treatment. A presentation by Dr. Bill Graham at the 2004 meeting of the American Society of Colon and Rectal Surgeons showed improvement in 10 of 11 patients using the cream BID17. When used intravaginally patients are taught to carefully protect the normal vulvar mucosa from burns with Efudex™. Can cause ulcerations and careful follow up is recommended. When used externally, a fine thin layer is put on the areas of treatment with generally little adverse effects seen.

   Indications: Unknown efficacy. Possibly for external anal warts, LSIL or HSIL. Unknown effects for internal disease. Used for treatment of extensive vaginal warts and vulvar warts, but no longer recommended by the CDC.