Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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Brian Berman and Sadegh Amini
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
External anogenital warts develop on the skin and mucosal surfaces of the genitalia and perianal areas. They are caused by the human papillomavirus (HPV), sexually transmitted in approximately 65% of cases, with at least 40 of the more than 100 types identified capable of infecting the genital tract. Condyloma acuminata (CA), the classic form of anogenital warts, and the more difficult to detect flat condylomata, are frequently associated with ‘benign’ HPV types 6 and 11 (up to 95%), but may also be caused by oncogenic HPV types such as 16, 18, 31, 33, and 35.
Most cases are asymptomatic; however, they can be disfiguring, lead to physical discomfort, induce psychological suffering, guilt, anger, and severely impact the patient’s quality of life. Untreated genital warts may increase in size or number, remain unchanged, or resolve spontaneously.
The treatment of external genital warts depends on patient preference, resource availability, and provider experience.
Current treatments focus on stimulation of the host’s immune response to enhance virus recognition. Treatments are categorized as either patient-applied (i.e., podofilox, imiquimod, and sinecatechin) or provider-administered. Podofilox (podophyllotoxin) is applied twice daily for 3 days, then no treatment for 4 days for four to six cycles, if necessary.
Imiquimod 5% or 3.75% cream stimulates the host’s immune response. Imiquimod 5% is applied overnight and washed off 6 to 10 hours after application, three times a week, until clearance of the warts or a maximum of 16 weeks. Imiquimod 3.75% is applied nightly for up to 8 weeks.
Sinecatechin 15% ointment extract of green tea from Camellia sinensis contains epigallocatechin gallate, exhibiting antiviral, antitumor and immunostimulatory properties. It is applied three times a day until clearance of the warts or a maximum of 16 weeks.
Provider-administered therapies are either topically applied or surgical. Topical modalities include podophyllin resin, podofilox (podophyllotoxin), bichloroacetic acid (BCA) and trichloroacetic acid (TCA). Surgical treatments include cryotherapy, surgical removal either by tangential shave using a cold knife or tangential scissor excisions, curettage with or without electrosurgery and lasers (CO2 and pulsed dye laser, PDL). Intralesional interferon-α is also an effective therapy. Podophyllin-applied resin is applied for 1 to 6 hours and is less effective on dry areas such as the penile shaft, scrotum, and labia majora.
The safety of podofilox, imiquimod, and sinecatechin (all category C) during pregnancy has not been established. Both TCA and BCA 80–90% solutions are applied weekly as needed.
Cryotherapy causes thermolysis and necrosis of keratinocytes hosting HPV. Liquid nitrogen either with cryospray or cryoprobe usually requires one to two freeze–thaw cycles per session for two to three sessions. However, HPV DNA is detectable up to 1 cm from the wart periphery, and recurrence rates are up to 40%, limiting the practicality of this modality.
Surgery and CO2 lasers are useful for treating extensive, giant (i.e., Buschke–Lowenstein tumor), intraurethral, and recalcitrant warts.
Recombinant HPV quadrivalent (6–11–16–18) vaccine is safe and efficacious in decreasing the incidence of persistent anogenital warts and cervical cancer by 90%, and is approved for females and males aged 9 to 26 years.
Estimates of clearance and recurrence rates with various therapies are difficult due to differences in method of analysis, patient population, and duration of follow-up. Over the years many treatment modalities have emerged, but no single treatment has proved superior to others. No available therapy can be guaranteed to clear genital warts without any recurrence. Combination therapy using an immunomodulator after a physical ablative therapy reduces recurrence rates; however, the possibility of additive adverse events should be considered.
Papanicolaou (Pap) smear
HPV typing (not standard of care)
Biopsy
Acetic acid 3%-5% (not recommended)
Kulasingam SL, Hughes JP, Kiviat NB, Mao C, Weiss NS, Kuypers JM, et al. JAMA 2002; 288: 1749–57.
HPV DNA testing has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings (i.e., long or haphazard screening intervals), HPV DNA screening may be an alternative to cytology-based screening in women of reproductive age.
Thornsberry L, English JC. J Pediatr Adolesc Gynecol 2012; 25: 150–4.
The diagnosis of anogenital warts is generally clinical. HPV DNA typing and 3–5% acetic acid testing to reveal subclinical lesions are not recommended. Anoscopy, and/or speculum examination are useful for evaluation of the anal canal, vagina, or cervix. A biopsy is not indicated for typical condylomas; however, it must be performed for atypical-looking and recalcitrant lesions or in immunocompromised patients.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Imiquimod (5%, 3.75%)
Podofilox (podophyllotoxin)
Sinecatechin extract of green tea
Cryotherapy
