Mucosal human papillomavirus (HPV) infections are the most common sexually transmitted disease (STD). When clinically symptomatic, lesions are barely visible papules to nodules to confluent masses occurring on anogenital or oral mucosa or skin, caused by infection with a mucosal type of HPV. Only 1 to 2% of HPV-infected individuals have any visibly detectable clinical lesion. HPV present in the birth canal can be transmitted to a newborn during vaginal delivery and can cause external genital warts (EGW) and respiratory papillomatosis. HPV dysplasia of the anogenital skin and mucosa ranging from mild to severe to squamous cell carcinoma (SCC) in situ (SCCIS); invasive SCC can arise within SCCIS, most commonly in the cervix and anal canal.
Causes of Human Papillomavirus: Mucosal Infections
“Low-risk” and “high-risk” HPV types both cause EGW. HPV infection probably persists throughout a patient’s lifetime in a dormant state and becomes infectious intermittently. Exophytic warts are probably more infectious than subclinical infection.
Immunosuppression results in new expression of HPV lesions, progression of HPV lesions, no increased rate of HPV infection but an increased risk of transmission, increased multifocal intraepithelial neoplasia. Immunosuppressed renal transplant recipients have a 17-fold greater incidence of genital HPV infection.
All HPV types replicate exclusively in host’s cell nucleus. In benign HPV-associated lesions, HPV exists as a plasmid in cell’s cytoplasm, replicating extrachromosomally. In malignant HPV-associated lesions, HPV integrates into host’s chromosome, following a break in the viral genome (around E1/E2 region). E1 and E2 function is deregulated, resulting in cellular transformation.
Diagnosis
Clinical diagnosis, occasionally confirmed by biopsy.
Treatment
Indications for Therapy Cosmetic; reduce transmissiblity; provide relief of symptoms; improve self-esteem.
Primary Goal of Treating Visible Genital Warts Removal of symptomatic Warts. Treatment can induce wart-free periods in most patients. Genital warts are often asymptomatic. No evidence indicates that currently available treatments eradicate or affect the natural history of HPV infection. Removal of warts may or may not decrease infectivity. If untreated, visible genital warts may resolve on their own, remain unchanged, or increase in size and number. No evidence indicates that treatment of visible warts affects the development of cervical or anal cancer.
Subclinical Genital HPV Infection (without exophytic warts) Subclinical genital HPV infection in much more common than exophytic warts among both men and women. Infection is often indirectly diagnosed on the cervix by Pap smear, colposcopy, or biopsy and on the penis, vulva, and other genital skin by the appearance of white areas after application of acetic acid. Treatment is not indicated.
External genital/perianal warts
Patient-applied agents
Imiquimod, 5% cream (Aldara) Mechanism of action is via local cytokine release (interferon, tumor necrosis factor interleukin). No direct antiviral activity. The cream, which is supplied in single dose packets, is applied to the involved site by the patient, three times per week, usually at bedtime. Some patients experience local irritation. Treatment duration up to 16 weeks.
Podofilox (Condylox) .5% solution and gel. A purified and stable Preparation of the active agent in podophyllin. Solution applied with a cotton swab and gel with a finger to condylomata and/or site involved (including normal-appearing skin between lesions) twice daily for 3 days, followed by 4 days of no therapy. This cycle may be repeated as necessary for a total of four cycles. Total area of treatment should not exceed 10 cm², and total volume should not exceed .5 mL/d. The health care provider should apply the initial treatment to demonstrate the proper application technique and identify lesions and sites to be treated. Podofilox is contraindicated during pregnancy.
Clinician-administered Therapy
Cryosurgery with liquid nitrogen Apply with cotton swab or cryospray. Repeat weekly or bi-weekly. Relatively inexpensive, does not require anesthesia, and does not result in scarring.
Podophyllin, 10 to 25% In compound tincture of benzoin. Limit the total volume of podophyllin solution applied to ≤.5 mL or ≤ 10 cm² per session. Thoroughly wash off in 1 to 4 h. Treat < 10 cm² per session. Repeat weekly if necessary. If warts persist after six applications, other therapeutic methods should be considered. Podophyllin contraindicated during pregnancy. Repeated application may cause irritation.
Trichloroacetic Acid (TCA) or Bichloroacetic acid bicarbonate (BCA), 80 to 90% Apply only to warts: powder with talc or sodium (baking soda) to remove unreacted acid. Repeat weekly if necessary. If warts persist after six applications, other therapeutic methods should be considered.
Surgical Removal Either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.
Electrodesiccation/electrocautery Highly effective in destruction of infected tissue ana HPV. Should be attempted only by clinicians trained in the use of this modality. Electrodesiccation is contraindicated in patients with cardiac pacemakers.
Carbon Dioxide Laser and Electrodesiccation Useful in management of extensive warts, particularly for those patients who have not responded to other regimens; not appropriate for treatment of limited lesions.
Cervical Warts
For women who have exophytic cervical warts, high-grade squamous intraepithelial lesions (SIL) must be excluded before treatment is begun. Management of exophytic cervical warts should include consultation with an expert.
Vaginal Warts
Cryosurgery with Liquid Nitrogen This modality is difficult due to “fog” formation, which restricts visualization of lesions.
TCA or BCA, 80 to 90% Applied to warts only, powder with talc or sodium bicarbonate to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary.
Podophyllin, 10 to 25% In compound tincture of benzoin. Treated area must be dry before the speculum is removed. Treat with ≤2 cm² per session. Repeat application at weekly intervals. Systemic absorption is a concern.
Urethral Meatus Warts
Cryosurgery with Liquid Nitrogen As above.
Podophyllin, 10 to 25% In compound tincture of benzoin. Treated area must be dry before contact with normal mucosa. Wash off in 1-2 h. Repeat weekly if necessary. If warts persist after six applications, other therapeutic methods should be considered.
Anal Warts
Management of warts on rectal mucosa should be referred to an expert.
Cryosurgery with Liquid Nitrogen As above.
TCA or BCA, 80 to 90% Apply to warts only, powder with talc or sodium bicarbonate (baking soda) to remove unreacted acid. Repeat weekly if necessary. If warts persist after six applications, other thera peutic methods should be considered.
Surgical removal As above.
Oral Warts
Cryosurgery with Liquid Nitrogen As above.
Surgical Removal As above.
Follow-up After visible warts have cleared, a follow-up evaluation is not mandatory. Patients should be cautioned to watch for recurrences which occur most frequently during the first 3 months. Because the sensitivity and specificity of self-diagnosis of genital warts are unknown, patients concerned about recurrences should be offered a follow-up evaluation 3 months after treatment. Earlier follow-up visits also may be useful to document a wart-free state, to monitor for or treat complications of therapy, and to provide the opportunity for patient education and counseling. Women should be counseled about the need for regular cytologic screening as recommended for women without genital warts. The presence of genital warts is not an indication for cervical colposcopy.
Immunosuppressed Patients Persons who are immunosuppressed because of HIV or other reasons may not respond as well as immunocompetent persons to therapy for genital warts and may have more frequent recurrences after treatment. SCC arising in or resembling genital warts might occur more frequently among immunosuppressed persons, requiring more frequent biopsy for confirmation of diagnosis.
Management of Sex Partners Examination of sex partners is not necessary because role of reinfection is probably minimal. Most partners are probably already subclinically infected with HPV, even if no warts are visible.
Prevention
Use of condoms reduces transmission to uninfected sex partners. Goal of treatment is removal of exophytic warts and amelioration of signs and symptoms-not eradication of HPV. No therapy has been shown to eradicate HPV. Treatment is more successful if warts are small and have been present for < 1 year. Risk of transmission might be reduced by “debulking” genital warts. Selection of treatment should be guided by preference of patient-expensive therapies, toxic therapies, and procedures that result in scarring avoided.
References