TREATMENT HPV-Associated Lesions OVERVIEW AND GENERAL RECOMMENDATIONS
A variety of treatment modalities are available for various HPV infections, but none has been proven to eliminate HPV from tissue adjacent to the destroyed and infected tissue. Treatment efficacies are limited by frequent recurrences (presumably due to reinfection acquired from an infected partner), reactivation of latent virus, or autoinoculation from nearby infected cells. The goals of treatment include prevention of virus transmission, eradication of premalignant lesions, and reduction of symptoms.
Treatment is generally successful in eliminating visible lesions and grossly diseased tissue. Different therapies are indicated for genital warts, vaginal and cervical disease, and perianal and anal disease.
An optimal therapy for HPV-related genital tract disease that combines high efficacy, low toxicity, low cost, and low recurrence rate is not available. For genital warts of the penis or vulva, cryotherapy (see below) is safest, least expensive, and most effective. Guidelines for the treatment of genital warts can be found on the CDC website (www.cdc.gov/std/treatment/2010/genital-warts.htm). Women with vaginal lesions should be referred to a gynecologist experienced in colposcopy and treatment of these lesions. Treatment of cervical disease involves careful inspection, biopsy, and histopathologic grading to determine the severity and extent of disease. Women with evidence of cervical HPV infection should be referred to a gynecologist familiar with HPV and experienced in colposcopy. Optimal follow-up of these patients includes colposcopic examination of the cervix and vagina on a yearly basis. Guidelines from the American College of Gynecology and Obstetrics are available for the treatment of cervical dysplasia and cancer.
For anal or perianal lesions, cryotherapy or surgical removal is safest and most effective. Anoscopy and/or sigmoidoscopy should be performed when patients have perianal lesions, and suspicious lesions should be biopsied to rule out malignancy. THERAPEUTIC OPTIONS
Tables 94-1 and 94-2 list the available patient-administered and physician-administered treatments, respectively. Podophyllotoxin
Podophyllotoxin (0.05% solution or gel and 0.15% cream) induces necrosis of genital wart tissue that heals within a few days. It is relatively effective and can be self-administered. Podophyllotoxin is applied twice daily on three consecutive days of the week for a maximum of 4 weeks. Adverse effects are common and include pain, inflammation, erosion, and burning or itching. Podophyllotoxin should not be used to treat vaginal, cervical, or anal lesions. The safety of podophyllotoxin during pregnancy has not been established. Sinecatechins
Sinecatechins (15% ointment) is used to treat genital warts but should not be used to treat vaginal, cervical, or anal lesions. Sinecatechins causes an inflammatory response when applied topically three times a day for up to 4 months. Clearance rates approach 60% in some studies, and recurrence rates are 6–9%. Adverse effects (redness, burning, itching, and pain at the site of application) are generally mild. The safety of sinecatechins during pregnancy is unknown. Imiquimod
Imiquimod (5% or 3.75% cream) is a patient-applied topical immunomodulatory agent thought to activate immune cells by binding to a Toll-like receptor—an event that leads to an inflammatory response. Imiquimod 5% cream is applied to genital warts at bedtime three times per week for up to 16 weeks. Warts are cleared in ~56% of patients, more often in women than in men; recurrence rates approach 13%. Local inflammatory side effects are common. Rates of clearance of genital warts with the 3.75% formulation are not as high, but the duration of treatment is shorter (i.e., daily application for a maximum of 8 weeks), and fewer local and systemic adverse reactions occur. Imiquimod should not be used to treat vaginal, cervical, or anal lesions. The safety of imiquimod during pregnancy has not been established. Cryotherapy
Cryotherapy (liquid nitrogen) for HPV-associated lesions causes cellular death. Genital warts usually disappear after two or three weekly sessions but often recur. Cryotherapy, which is nontoxic and is not associated with significant adverse reactions, can also be used for diseased cervical tissue. Local pain occurs frequently. Surgical Methods
Exophytic lesions can be surgically removed after intradermal injection of 1% lidocaine. This treatment is well tolerated but can cause scarring and requires hemostasis. Genital warts can also be destroyed by electrocautery, in which no additional hemostasis is required. Laser Therapy
Laser treatment affords destruction of exophytic lesions and other HPV-infected tissue while preserving normal tissue. Local anesthetics are generally adequate. Efficacy for genital lesions is at least equal to that of other therapies (60–90%), with low recurrence rates (5–10%). Complications include local pain, vaginal discharge, periurethral swelling, and penile or vulvar swelling. Laser therapy has also been used successfully to treat cervical dysplasia and anal disease caused by HPV. Interferon (IFN)
Recombinant IFN-α is used for intralesional treatment of genital warts, including perianal lesions. The recommended dosage is 1.0 × 106 IU of IFN injected into each lesion three times weekly for 3 weeks. IFN therapy causes clearance of infected cells by immune-boosting effects. Adverse events include headache, nausea, vomiting, fatigue, and myalgia. IFN therapy is costly and should be reserved for severe cases that do not respond to cheaper treatments. IFN should not be used to treat vaginal, cervical, or anal lesions. Other Therapies
Both trichloroacetic acid and bichloroacetic acid are caustic agents that destroy warts by coagulation of proteins. Neither of these agents is recommended for treatment.