Treatments for genital warts

Journal of Drugs in Dermatology, August, 2008 by Kathleen Cook

INTRODUCTION

Anogenital warts, or condyloma acuminata, are a common manifestation of sexually transmitted human papillomavirus (HPV) infections, and represent a significant public health concern. Multiple medical and surgical treatment options are available for genital warts. Because condyloma can be recalcitrant to therapy and recur frequently, familiarity with the treatment options for genital warts can help practitioners optimize management in difficult cases. With the advent of HPV vaccines, the prevention of genital warts can also be considered.

Genital warts are caused by a HPV infection. Human papillomaviruses are small, nonenveloped viruses containing a circular double-stranded DNA genome that encodes 6 early genes and 2 late genes. There are over 118 recognized HPV types, conferring a wide disease spectrum. (1) Human papillomavirus types are categorized as high-risk or low-risk based upon the potential malignancy. Low-risk HPV (types 6 and 11) are the most common causes of visible genital warts. Human papillomavirus types 16 and 18 have the highest malignancy potential and are associated with squamous intraepithelial neoplasia, vaginal, cervical, and anal intraepithelial dysplasia, and squamous cell carcinoma. (2)

Genital warts are the most commonly diagnosed sexually transmitted disease (STD) in the developing world. According to the Centers for Disease Control and Prevention (CDC), 18.3% of female adolescents in the US have HPV. (3) More than 6 million people are infected with genital HPV in the US each year, nearly half in individuals between 15 and 25 years of age. (4) Approximately 10% of men and women will develop genital warts in their lifetime. (4) Genital HPV infections are transmitted through sexual contact. (5) Epidemiological data from the US shows that while only 1% of the sexually active population presents with anogenital warts, 5% to 20% are infected with HPV. (5) The incidence of anogenital warts in HIV-infected homosexual males is as high as 40%. (6)

Basal keratinocytes are the target for HPV infection. As kertinocytes differentiate, cornified cells containing virions are desquamated and deposited on the sex partner, where mechanical stress causes a release of the infectious particles. (7) Barrier protection, such as the use of condoms, reduces the risk of transmission, but does not protect against condylomas at the base of the penis shaft or other uncovered regions of the genitalia. After infection, incubation periods up to months in duration are possible before clinical lesions are detectable, and many infections remain subclinical. After initial infection, HPV can remain latent for years with later reactivation.

The treatment of genital warts causes frustration for physicians and patients because most therapeutic modalities require multiple treatments with frequent follow-up visits, but have low cure rates and high-recurrence rates (Table 1). (8) Reported clearance rates with treatment range from 23% to 100% compared to 0% to 50% for a placebo. (2) Presumably, spontaneous resolution of HPV infections depends on the patient's immune response. Likewise, treating genital warts in immunocompromised patients is particularly difficult because they typically have more extensive lesions and experience higher recurrence rates.

Therapeutic options for genital warts comprise both medical and surgical treatment modalities. Medical treatments include patient-applied topical agents such as imiquimod, podophyllotoxing, and 5-fluorouracil. Physician-administered medical treatments include topical trichloroacetic acid (TCA) and podophyllin, or intralesional agents such as interferon or bleomycin. Surgical approaches include cryotherapy, electrosurgery, excision, and laser therapy. (9) The primary treatment endpoint is elimination of visible warts. Whether this reduces persistence of HPV DNA in tissue, therefore reducing infectivity, has not been studied systematically. Similarly, no evidence exists that treatment decreases the incidence of cervical and genital cancer. Recently developed vaccines against HPV present the first realistic opportunity for primary prevention of infection and HPV-related malignancy.

Approaches To Treatment

There are a wide variety of treatment options for anogenital warts. Some therapies are based on long-standing historical practice, with little data available from controlled trials. Moreover, no data show the superiority of one method over another; however, randomized controlled trials suggest that imiquimod, podophyllotoxin, cryotherapy, TCA, and intralesional interferons (IFNs) are more effective than a placebo, and that most surgical methods are generally equivalent. (10)

The most common treatment modalities for anogenital warts are reviewed here. The primary goal of treatment is to alleviate discomfort by eliminating symptomatic warts. Because no one approach is proven superior, treatment selection is a matter of physician and patient preference. Prior to any treatment, clinically suspicious lesions should be biopsied to rule out squamous cell carcinoma.