External Genital Warts: An Update
External Genital Warts: An Update External Genital Warts: An Update
Mayeaux TABLE. Centers for Disease Control and Prevention Recommended Regimens for Condylomata Acuminata Location Treatment Comments External genital warts Podofilox 0.5% solution Imiquimod, podophyllin, and Imiquimod 5% cream podofilox are contraindicated in Cryotherapy pregnancy Podophyllin resin 10%-25% in tincture of benzoin Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80%-90% Surgical removal External genital warts, Sinecatechins 15%* Systemic interferon is not effective alternative regimens Laser surgery and not recommended as a primary Intralesional interferon modality Extensive genital warts Imiquimod 5% cream* These modalities can be applied to Laser surgery* large areas to reduce or treat Sinecatechins 15%* extensive lesions. Imiquimod, podophyllin, and podofilox are contraindicated in pregnancy Warts during pregnancy Cryotherapy with liquid nitrogen or cryoprobe TCA or BCA 80%-90% Surgical removal Cesarean delivery should not be performed solely to prevent HPV transmission to the newborn Vaginal warts Cryotherapy with liquid nitrogen The use of a cryoprobe in the vagina TCA or BCA 80%-90% is not recommended because of the risk for vaginal perforation and fistula formation Urethral meatus warts Cryotherapy with liquid nitrogen Some specialists recommend Podophyllin 10%-25% in podofilox and imiquimod in these tincture of benzoin patients, but the data are limited Anal warts Cryotherapy with liquid nitrogen Also inspect for rectal warts using TCA or BCA 80%-90% digital examination or anoscopy Surgical removal *Author’s recommendations. DIAGNOSIS There are no specific screening tests for external HPV lesions, which are usually identified visually. Although usually unnecessary, detection of flat HPV lesions can be enhanced with the use of a colposcope or hand lens and 5 minutes’ application of 5% acetic acid. A biopsy should be obtained from any lesion that has an atypical appearance, is pigmented, or is resistant to therapy. Histologic examination of HPV lesions usually demonstrates koilocytic atypia, including enlarged cells with perinuclear halos and hyperchromatic nuclei. Tests for HPV DNA typing are not indicated for external lesions. 11 The Female Patient VOL. 32 DECEMBER 2007 41
CME External Genital Warts The differential diagnosis for HPV lesions includes condyloma latum (syphilis), which presents as smooth, broad-based papules. Benign skin lesions such as seborrheic keratoses, nevi, microglandular hyperplasia, and hymenal remnants may occasionally be confused with condylomata. Molluscum contagiosum and herpetic lesions must be excluded as well. More serious HPV mimics include bowenoid A higher index of suspicion for malignancy should be maintained for immunocompromised patients, atypical-appearing lesions, lesions refractory to treatment, and pigmented lesions. papulosis, malignant melanoma, and Buschke- Lowenstein tumor. 11 As squamous cell carcinomas may arise in or resemble genital warts, biopsy is recommended. It is very important to distinguish vulvar papillomatosis (a normal variant) from condylomata acuminata, because inappropriate treatment may produce chronic pelvic pain. Warts, dysplasia, and cancer all may be similar in appearance. A higher index of suspicion for malignancy should be maintained for immunocompromised patients, atypical-appearing lesions, lesions refractory to treatment, and pigmented lesions. A biopsy should be obtained in these cases, but again, HPV typing is generally not useful. 12 THERAPY The CDC recommends that treatment be guided by patient preference (Table). 6 None of the available treatments is superior to the others, and no single treatment is ideal for all patients or all warts. Practitioners should be familiar with at least one patient-applied treatment and one provider-applied therapy. 6 No data suggest specific treatment modalities in the setting of concomitant human immunodeficiency virus (HIV) infection. Patient-applied Therapies Imiquimod.—Imiquimod/imidazoquinolinamine, 5% cream, is an immune modifier that induces cytokines. 13,14 It has almost no systemic side effects, and is classified as pregnancy category C. It may also help to induce “immune memory” and prevent future recurrences. 15 It is indicated for use on external HPV infections, and contraindicated for occluded mucous membranes (eg, vagina, urethra, perianal area, cervix). Condoms and diaphragms should not be used during treatment, as imiquimod may damage latex. The patient should apply it three times a week, every other day, for up to 16 weeks. The affected area should be washed with mild soap and water 6 to 10 hours after application. Side effects include erythema, erosion, itching, skin flaking, and edema. Clearance occurs within 16 weeks in 37% to 54% of patients, with recurrences noted in 13% to 19%. 9 Podofilox.—Podofilox/podophyllotoxin, 0.5% gel, solution, or cream, is the purified active component of podophyllin. It is contraindicated for use on occluded mucous membranes and during pregnancy. Podofilox is applied twice daily for 3 consecutive days followed by 4 consecutive days of no therapy (7 days total), repeated for a maximum of 4 weeks. Trials have shown that 45% to 77% of patients attained clearance within 4 to 6 weeks. Side effects include inflammation, irritation, erosion, burning, pain, and itching. Recurrences have been reported in 4% to 38% of patients. Effective contraception such as condoms/diaphragms for women of childbearing age is advised until the warts are cleared. 9 Sinecatechins.—Sinecatechins, 15% ointment, is a new botanical treatment derived from green tea, 16 and is FDA-approved for the treatment of external genital and perianal warts in patients aged 18 years or older. Catechins have shown chemopreventive properties against various cancers, 16 as well as antiangiogenic and anti-HPV activity and inhibition of tumor invasion. The ointment is applied by the patient three times a day for 16 weeks. Partial or total clearance has been reported in more than 77% of patients. Local skin reactions are mild to moderate, with rare instances of pain and inflammation. 17, 18 Sinecatechins is classified as pregnancy category C. 42 The Female Patient VOL. 32 DECEMBER 2007
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Mayeaux<br />
TABLE. Centers for Disease Control and Prevention Recommended Regimens<br />
for Condylomata Acuminata<br />
Location Treatment Comments<br />
<strong>External</strong> genital warts Podofilox 0.5% solution Imiquimod, podophyllin, and<br />
Imiquimod 5% cream<br />
podofilox are contraindicated in<br />
Cryotherapy<br />
pregnancy<br />
Podophyllin resin 10%-25%<br />
in tincture of benzoin<br />
Trichloroacetic acid (TCA) or<br />
bichloroacetic acid (BCA) 80%-90%<br />
Surgical removal<br />
<strong>External</strong> genital warts, Sinecatechins 15%* Systemic interferon is not effective<br />
alternative regimens Laser surgery and not recommended as a primary<br />
Intralesional interferon<br />
modality<br />
Extensive genital warts Imiquimod 5% cream* These modalities can be applied to<br />
Laser surgery*<br />
large areas to reduce or treat<br />
Sinecatechins 15%*<br />
extensive lesions. Imiquimod,<br />
podophyllin, and podofilox<br />
are contraindicated in pregnancy<br />
<strong>Warts</strong> during pregnancy Cryotherapy with liquid nitrogen<br />
or cryoprobe<br />
TCA or BCA 80%-90%<br />
Surgical removal<br />
Cesarean delivery should not be<br />
performed solely to prevent HPV<br />
transmission to the newborn<br />
Vaginal warts Cryotherapy with liquid nitrogen The use of a cryoprobe in the vagina<br />
TCA or BCA 80%-90%<br />
is not recommended because of the<br />
risk for vaginal perforation and<br />
fistula formation<br />
Urethral meatus warts Cryotherapy with liquid nitrogen Some specialists recommend<br />
Podophyllin 10%-25% in<br />
podofilox and imiquimod in these<br />
tincture of benzoin<br />
patients, but the data are limited<br />
<strong>An</strong>al warts Cryotherapy with liquid nitrogen Also inspect for rectal warts using<br />
TCA or BCA 80%-90%<br />
digital examination or anoscopy<br />
Surgical removal<br />
*Author’s recommendations.<br />
DIAGNOSIS<br />
There are no specific screening tests for external<br />
HPV lesions, which are usually identified<br />
visually. Although usually unnecessary,<br />
detection of flat HPV lesions can be enhanced<br />
with the use of a colposcope or hand lens and<br />
5 minutes’ application of 5% acetic acid. A<br />
biopsy should be obtained from any lesion<br />
that has an atypical appearance, is pigmented,<br />
or is resistant to therapy. Histologic examination<br />
of HPV lesions usually demonstrates<br />
koilocytic atypia, including enlarged cells with<br />
perinuclear halos and hyperchromatic nuclei.<br />
Tests for HPV DNA typing are not indicated<br />
for external lesions. 11<br />
The Female Patient VOL. 32 DECEMBER 2007 41
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