TREATMENT HPV-Associated Disease
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 from an infected partner, reactivation of latent virus, or autoinoculation from nearby infected cells. The goals of treatment include prevention of viral transmission, eradication of premalignant lesions, and reduction of symptoms.
Therapies are 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. THERAPEUTIC OPTIONS 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 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 are not as high with the 3.75% formulation as with the 5% preparation, but the duration of treatment is shorter (daily application required 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. Interferon
Recombinant interferon α is used for intralesional treatment of genital warts, including perianal lesions. The recommended dosage is 1.0 × 106 IU of interferon into each lesion three times weekly for 3 weeks. Interferon therapy causes clearance of infected cells by immune-boosting effects. Adverse events include headache, nausea, vomiting, fatigue, and myalgia. Interferon therapy is costly and should be reserved for severe cases that do not respond to less expensive treatments. Interferon should not be used to treat vaginal, cervical, or anal lesions. Cryotherapy
Cryotherapy (liquid nitrogen treatment) 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 for cervical dysplasia and anal disease caused by HPV. Therapeutic Vaccines
The innate and adaptive immune systems are altered in patients with HPV-associated cancers. Antitumor immune responses are blunted by specific viral mechanisms. Numerous therapeutic vaccines that are being developed are designed to enhance the cell-mediated response to the HPV E6 and E7 oncoproteins, which are expressed in HPV-associated cancers. Such vaccines would enhance the ability to treat HPV-associated cancers, conditions that are very difficult to treat with current modalities. However, while progress has been made, no HPV vaccine is currently available for treatment of HPV infection or HPV-associated disease. 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. Sinecatechins (15% ointment) and podophyllotoxin (0.05% solution or gel and 0.15% cream) are occasionally used for external genital warts, but other modalities listed above are as or more effective and are better tolerated. RECOMMENDATIONS FOR TREATMENT
Table 193-1 lists available treatments for genital warts. An optimal therapy for HPV-related genital tract disease that combines high efficacy, low toxicity, low cost, and low recurrence is not available. For genital warts of the penis or vulva, cryotherapy is the safest, least expensive, and most effective modality. However, all available modalities for treatment of genital warts carry high rates of recurrence. Guidelines for the treatment of genital warts can be found on the CDC website (http://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 HPV-associated cervical disease 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 Obstetricians and Gynecologists 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 in patients with perianal lesions, and suspicious lesions should be biopsied to rule out malignancy.