Monday, October 15, 2007

Condyloma (genital warts) in women

INTRODUCTION — Condyloma acuminata (genital warts) are the most common sexually transmitted condition in the United States. Although warts affect both genders, one study showed that women accounted for 67 percent of patients.

CAUSES — Condyloma are caused by the human papillomavirus (HPV), which infects the epithelial layer (the outer layer) of the skin and mucous membranes. Over 70 different types of HPV have been identified, each of which infects a specific area of the body. Researchers have labeled the HPV types as being at high or low risk for causing cervical cancer. The HPV viruses that cause most genital warts are low-risk types. HPV types 6 and 11 are a major cause of warts, and types 16 and 18 are major causes of cervical cancer. (See "Patient information: Screening for cervical cancer").

HPV is spread by direct skin-to-skin contact, including sexual intercourse, oral sex, anal sex, or any other contact involving the genital area (eg, hand to genital contact). It is not possible to become infected with HPV by touching a toilet seat.

SYMPTOMS — Rarely, women with genital warts have itching, burning, or tenderness in the genital area, depending upon the number of warts and their location. However, most women with warts do not have any symptoms at all.

Warts appear skin-colored or pink, and may be smooth and flat or raised with a rough texture. They are usually located on the labia or at the opening of the vagina, but can also be around or inside the anus (show picture 1).

Warts may appear weeks to a year or more after HPV exposure; it is not usually possible to know when, how, or from whom the infection was transmitted.

DIAGNOSIS — Most women with genital warts can be diagnosed based upon a healthcare provider's visual examination. In some women, further examination with colposcopy (examination of the vulva, vagina, and cervix) or anoscopy (examination of the anus and rectum) is recommended. For these tests, the healthcare provider uses a magnifying device to closely inspect the skin or tissue for evidence of HPV infection. A weak acid solution (called acetic acid) is applied to the skin or tissue, which can further aid in the diagnosis; this does not cause pain.

A biopsy (removal of a small piece of tissue) is recommended if the provider is uncertain whether the area in question is a genital wart, if the wart does not respond to treatment, if the lesion is very large, if the patient has a weakened immune system due to HIV or medications, or if the lesion has an unusual appearance. Most women with genital warts will not need a biopsy.

TREATMENT — Treatment of warts usually involves a topical medication that is applied by the patient or healthcare provider. Other treatments, such as oral medications and surgery, are generally reserved for patients with very large areas of warts or warts that do not improve with topical treatments. A summary of these treatments is provided here (show table 1).

To eliminate the wart(s); a course of treatment over several weeks is generally required. Even with treatment, it may not be possible to eradicate the HPV virus from the genital area; therefore, it is possible that the warts will recur. There is currently no treatment that will eradicate the HPV virus itself.

Treatment is not necessary if the warts are not bothersome. Furthermore, 10 to 30 percent of genital warts will resolve on their own without treatment

Medical treatments — Medical treatments include medications that are applied directly to the wart. There are two broad categories of medical therapy: those that directly destroy the wart tissue (cytodestructive therapies) and those that work through the patient's immune system to clear the wart (immune-mediated therapies). Some treatments must be applied in the healthcare provider's office while others can be applied by the patient at home.

Podophyllin — Podophyllin is a plant-based resin that destroys the wart tissue. It is only used for vulvar lesions; using it on the cervix or vaginal tissues can cause chemical burns. The healthcare provider applies the solution directly to the warts with a cotton swab, and the patient should wash the area one to four hours later to avoid excessive skin irritation. The treatment is repeated weekly for four to six weeks, or until the lesions have cleared.

Studies have reported 40 to 75 percent of patients are cleared of warts after using podophyllin, but 25 to 100 percent have a recurrence over time [1]. Adverse effects range from mild skin irritation to ulceration and pain.

Podophyllotoxin — Podophyllotoxin (Condylox®) contains the biologically active compound from podophyllin, but it can be self-administered. Using a cotton swab, the patient applies a 0.5 percent gel or liquid solution to the warts twice daily for three consecutive days. No more than 0.5 ml of medication should be used per treatment session, and no more than a 3 cm by 3 cm area should be treated. No treatment is used for the following four days; the treatment cycle can be repeated up to four times until the warts have resolved.

Clinical studies have described wart clearance rates of 29 to 90 percent [2]. Podophyllotoxin may be recommended as a first-line treatment if the patient is willing and able to apply it. Podophyllotoxin may be more effective than podophyllin.

Bichloroacetic acid and trichloroacetic acid — Both bichloroacetic acid (BCA) and trichloroacetic acid (TCA) are acids that destroy the wart tissue. TCA is used most commonly, and must be applied by a health care provider. An 80 to 90 percent TCA solution is applied sparingly to the wart tissue, which will turn white as the solution dries. Petroleum jelly may be applied to the normal tissue surrounding the wart to prevent the acid from reaching these areas. Once weekly application is required for four to six weeks, or until the lesions have cleared. Side effects of TCA may include pain and burning.

One trial that evaluated TCA in women showed a 70 percent clearance rate [3]. In contrast to podophyllin, TCA can be used on the cervix and vagina, and is safe for use during pregnancy.

Imiquimod — Imiquimod (Aldara®) is a cream that causes an immune response; this causes the body to eliminate the wart. The patient applies the cream directly to the wart tissue (generally at bedtime), and then washes the area with water six to 10 hours later. The drug is applied every other day for a total of three days per week, for up to 16 weeks. Side effects may include mild irritation and redness. Imiquimod should not be used internally on vaginal warts, and it is not recommended for use during pregnancy.

Randomized trials show a 50 percent clearance rate with 10 to 20 percent recurrence rates [4].

Interferon — Interferon is a medication that causes an immune response. It is available in several treatment forms (intramuscular injection, topical gel, subcutaneous injection), but studies have determined that it most effective when given as a subcutaneous (under the skin) injection at the base of the wart two to three times per week for up to nine weeks. Several clinical trials have shown clearance rates of about 20 to 60 percent [5], although other trials have failed to show any benefit [6], perhaps due to too brief a period of follow-up.

Side effects of interferon include flu-like symptoms, fatigue, lack of appetite, and local pain. Given these side effects, the variable rates of effectiveness, and the need for multiple treatments per week, interferon is not generally recommended as a first-line treatment. It may be used in combination with surgical and/or other medical treatments, especially in patients with warts that do not improve with other treatments.

Interferon is not safe for use during pregnancy.

Surgical treatment — Surgery is generally reserved for patients with: Lesions that do not respond to medical therapy Extensive or bulky disease, where medical therapy alone is often inadequate Lesions involving the vagina, urethra, or anus Areas that have associated pre-cancerous changes

Surgical management options include excisional (removal) and ablative (destructive) procedures. These treatments are often used in a combined fashion.

Cryotherapy — Cryotherapy uses a chemical (either nitrous oxide or liquid nitrogen) to freeze the wart tissue. The treatment can be done in a healthcare provider's office, and does not usually require any anesthesia. Studies have reported 50 to 80 percent clearance of warts after cryotherapy. Cryotherapy can be used during pregnancy.

Cryotherapy often causes pain during the procedure; other side effects can include skin irritation, swelling, blistering, and ulceration. For these reasons, medical therapies, such as podophyllin, podophyllotoxin, and trichloroacetic acid may be recommended before trying cryotherapy.

Electrocautery — Electrocautery uses electrical energy to burn away wart tissues. Patients are treated in an operating room after receiving local anesthesia to prevent pain. It can be used for vaginal lesions.

Excision — Excision involves the removal of an area of warts by surgically cutting it out. Most patients are treated in an operating room after receiving anesthesia to prevent pain. Rarely, excision causes pain, scar formation, and infection.

Excisional therapy is effective. Most studies show success rates of 36 to 100 percent and recurrence rates of 8 to 65 percent within one year [7].

Laser — Lasers produce light energy, which is absorbed by water within wart tissues, leading to its destruction. Physicians who perform laser treatment require specific training and specialized equipment. Patients are treated in an operating room after receiving local anesthesia to prevent pain.

Laser therapy is preferred when multiple warts are spread over a large area. Laser is also useful for treating cervical and vaginal warts, when surgical excision is not possible or would be difficult. Risks of laser surgery include scarring, pain, and changes in the skin's appearance (usually lightened color). Rarely, patients may develop chronic pain in the area of treatment.

Laser therapy clears lesions in 40 to 100 percent of warts, and long-term recurrences occur in 4 to 77 percent of patients.

Ultrasonic aspiration — The CUSA technique (Cavitron ultrasonic aspirator-CUSA) uses ultrasound (sound waves) to break up and remove warts. With this technique, removal of the outer layer of skin occurs without damage to underlying tissue. Patients are treated in an operating room after receiving general anesthesia to induce sleep and prevent pain. One study showed this technique to be effective in the treatment of warts [8]. CUSA requires that a healthcare provider undergo specialized training and purchase specialized equipment, so it is not widely available.

FOLLOW UP — Following successful treatment of warts, some patients will be instructed to examine themselves periodically to monitor for new warts; other patients will be asked to return to their healthcare provider at regular intervals for examination. Most patients who develop recurrent or persistent warts do so within three to six months of treatment. Recurrence is more common in persons with a weakened immune system (due to HIV or certain medications); more frequent follow-up or self-monitoring of these patients is reasonable so that treatment may begin promptly.

It is important to understand that complete elimination of visible warts does not necessarily mean that HPV has been eradicated. Therefore, warts may recur even after successful initial treatment. In this situation, the same treatment may be used again and is likely to be successful.

PREVENTION

HPV vaccine — A vaccine (Gardasil®) is now available to help prevent infection with some types of HPV (types 6, 11, 16, and 18), which in turn can prevent most cases of cervical cancer and genital warts. The vaccine was proven to be safe and effective in several large clinical trials [9,10].

The vaccine is currently recommended for all girls and women between ages 9 and 26 years. Decisions about the age at which to start HPV immunization have been guided by data regarding the ages of peak HPV infection and the estimated duration of vaccine protection. While it is not known exactly how long the vaccine protects against HPV infection, clinical trials prove protection for at least 4 years [11]. Further study is underway to determine if a booster shot is needed after this time.

The vaccine has not been studied in women over 26 years old and thus its effectiveness is uncertain. Women over this age are more likely to have been exposed to the four types of HPV (6, 11, 16, and 18), and the vaccine does not protect against viral strains to which the patient has already been exposed.

The vaccine is given by injection and requires three doses; the first injection is followed by a second and third dose two and six months later.

It is not known if vaccination of men could help to reduce the incidence of cervical cancer in women. Studies are currently underway to address this question.

Sexual contact — Avoiding contact with infected individuals is one way to reduce the risk of becoming infected or transmitting HPV. However, from a practical standpoint this is difficult, as many people are infected and do not have any signs or symptoms of infection. Condoms do not provide complete protection; contact (hand to genitals or genitals to genitals) involving areas not covered by the condom can result in transmission of HPV.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Cancer Society

(www.cancer.org, search for HPV)
National HPV and Cervical Cancer Public Education Campaign

Telephone: 1-866-280-6605
(www.cervicalcancercampaign.org)
National Institute of Allergy and Infectious Diseases

(www.niaid.nih.gov/factsheets/stdhpv.htm)
Center for Disease Control and Prevention

(www.cdc.gov/std/HPV/STDFact-HPV.htm)
American Social Health Association

(www.ashastd.org/hpv/hpv_learn.cfm)


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2. Greenberg, MD, Rutledge, LH, Reid, R, et al. A double-blind, randomized trial of 0.5% podofilox and placebo for the treatment of genital warts in women. Obstet Gynecol 1991; 77:735.
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13. Schiffman, MH, Bauer, HM, Hoover, RN, et al Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 1993; 85:958.
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