Topic

• Introduction
• Therapy
• Patient-Applied Treatments
• Provider-Applied Treatments
• Indications
• Contraindications
• Procedure
• Coding Information

Table(s)

• Differential Diagnosis for Condylomata Acuminata

Figure(s)

• Application of Podofilox
• Introducing a Medium-Sized Loop
• Shaving the Remaining Lesion
• Cryotherapy
• Injecting an Anesthetic to Raise a Wheal
• Shaving the Lesion

• Human papillomavirus (HPV) infects the active basal layers of skin through microabrasions that frequently occur during intercourse. Heterosexual and homosexual activity can spread HPV.
• A latency period of many years may occur before disease becomes apparent, making epidemiology and control of spread of the virus difficult.
• HPV lesions can usually be diagnosed by their gross appearance. Detection of flat HPV lesions can be enhanced using a colposcope and 5% acetic acid, which produces characteristic acetowhite changes. Any lesion that has an atypical appearance, is pigmented, or is resistant to therapy should be biopsied to rule out malignancy.
• Lab tests for detection of HPV DNA are not useful for external genital warts. There is no widely accepted screening test for diagnosis of external HPV lesions except physical exam (Table 41-1).
• External genital warts typically worsen during pregnancy.
  • Cesarean section is indicated only if condylomata physically obstruct the pelvic outlet, not to prevent HPV infection of newborn. Although infant exposure to maternal HPV is common, studies indicate that HPV rarely colonizes the baby.
  • Condylomata acuminata during pregnancy may be treated to reduce the risk of postpartum hemorrhage and poor healing in condylomatous tissue after delivery, but there are no published prospective studies of the efficacy of treating lesions to control these problems.
  • Use of 5-fluorouracil and podophyllin is contraindicated in pregnancy. Cryotherapy has been shown to be safe and effective, and it remains the treatment of choice during pregnancy.
• HPV 6 and 11 can cause laryngeal papillomatosis, but the route of transmission is not understood. Perinatal transmission rates are believed to be low, considering the high prevalence of maternal HPV infections and low rates of perinatal infection. 1 study suggested a transmission rate as high as 30% for babies born to mothers with latent HPV infection but also observed that all of the babies cleared HPV DNA by age 5 wks.
• Presence of genital HPV infection in children should arouse suspicion of child abuse. HPV lesions may be seen in girls and boys, and sexual and nonsexual routes of transmission have been identified.
  • Types of nonsexual transmission that have been documented include gestational, during birth, and from familial nonsexual contacts.
  • When HPV lesions are found, obtain thorough history, and consider testing for other sexually transmitted diseases. All U.S. states require that any suspected child abuse be reported to appropriate authorities.
• External genital warts are more prevalent and difficult to treat in patients with concomitant HIV infection, and the severity of HPV lesions worsens as HIV infection progresses. Increased risk of cervical and anal carcinoma has been found in women with HIV infection, and cervical dysplasia is part of the CDC criteria for AIDS. There is a need for careful, repetitive exam of the cervix and perineum of HIV-infected women.
• The goal of treating noncervical HPV infections is elimination of the obvious, symptomatic, or troublesome lesions—not eradication of the virus. Because many warts regress over time, treatments that do not have significant risk of scarring should be considered primarily. Modern approaches have a much better safety profile than older methods, but they are still plagued with high recurrence rates and variable success rates.
• Treating male sexual partners with HPV infection has not appeared to change posttreatment failure rate in women with cervical dysplasia. These findings should not deter the clinician from appropriately counseling, examining, and treating HPV-infected men.
• The epidemiology and transmissibility of HPV should be explained to the patient so that steps can be taken to decrease further spread. Inform patients that they are contagious to sexual partners. Sexual abstinence, monogamous relationships, and condoms may help decrease the spread of virus. However, condoms do not cover all areas where the virus infects, and they are imperfect barriers.

Therapy

• 5-Fluorouracil was once commonly used for many types of lesions. Cases of clear cell carcinoma arising in vaginal adenosis after 5-fluorouracil treatment for condylomas has been reported. These problems and the possibility of severe side effects have eliminated this drug as a preferred treatment modality.
• In 1998, Morbidity and Mortality Weekly Report published a list of recommended therapies, with several new therapies since that report.
• Treatment should be guided by patient preference.
• Practitioners should be familiar with at least 1 patient-applied treatment (i.e., imiquimod and podofilox) and 1 provider-applied therapy. Large exophytic lesions generally should be pared down before therapy.

Patient-Applied Treatments

Imiquimod Cream (Aldara)

• An immune-modifying agent that induces multiple subtypes of interferon-alpha, several cytokines, tumor necrosis factor, and interleukins. These factors activate natural killer cells, T cells, polymorphonuclear neutrophils, and macrophages that attack tumor.
• The drug has almost no systemic side effects and is a pregnancy class B drug.
• It may help induce immune "memory" and prevent future recurrence.
• Side effects can include erythema, erosion, itching, skin flaking, and edema. Therapy can be temporarily halted if symptoms become problematic. Imiquimod demonstrates clearance rates of 72% for women and 33% for men, with >50% wart reduction rates of 85% for women and 70% for men.
• It appears to work best on moist tissues, which may account for its higher success rates in women.

Podofilox (Condylox)

• Purified, active component of podophyllin. This purified form is better standardized, safer, and indicated for patient application.
• Podophyllin systemic reactions may occur with extensive application, after application to the mucous membranes, or if left on the skin for long periods. Reported reactions include nausea, vomiting, fever, confusion, coma, renal failure, ileus, and leukopenia. Pain and ulceration may also occur.
• Because repeated application to the mouse cervix produced dysplastic changes, its use on the human uterine cervix is not recommended. It works by inhibition of nuclear division at metaphase. Success rates vary from 44–88%.

Provider-Applied Treatments

Loop Electrosurgical Excisional Procedure (LEEP)

• Can be used to treat perineal condylomata in male and female patients. It may also produce tissue for pathologic study of lesions that are questionable or fail to respond to treatment as expected.
• HPV can be aerosolized, and HPV DNA has been found in laser and electrocoagulation smoke. Operators should wear a virus-filtering mask.
• LEEP has not been extensively studied in pregnancy.
• Loops used for removal of external lesions are smaller and shorter than standard cervical loops and are selected to allow easy removal of lesion. Power setting must be high enough to allow easy passage with low tissue drag through the lesion and epidermis.
• Smoke evacuator should be activated before performing LEEP. Anesthesia can be obtained with 1–2% lidocaine with epinephrine (except on the penis, where epinephrine generally is avoided).
• Follow-up protocols vary; typically, patients return in 2 wks to 1 month for follow-up, unless unexpected pain or infection becomes a problem. Late bleeding has been reported in 4% of patients treated for vaginal lesions, and it can usually be controlled with Monsel's solution or fulguration.
• Infection is an uncommon complication that is usually controlled with topical (and rarely, systemic) antibiotics. Hypopigmentation and hypertrophic scars are rarely reported.
• Success rates for treating noncervical lesions with LEEP are in the range of 90–96%.

Cryotherapy

• Works by freezing and killing abnormal tissue, which then sloughs off, and new tissue grows in its place. Local injection or topical anesthetic cream may be used but generally is unnecessary.
• Recalcitrant lesions can be treated with a freeze-thaw-refreeze technique to increase efficacy. Follow-up for retreatment is usually every 2 weeks until the lesion is resolved.
• The procedure does involve some pain during freezing and healing. Local infection and ulceration has been anecdotally reported.
• The success rate for cryotherapy is 71–79%.

Trichloroacetic Acid (TCA) and Bichloracetic Acid (BCA)

• Work by physically destroying tissue. Because they are quickly inactivated after contact with tissue, toxicity is not a problem.
• TCA can be prepared in different strengths and must be compounded at a pharmacy. BCA can be obtained in a standard prep.
• Follow-up schedule is every 1 to 3 weeks until the lesions resolve.
• The depth of penetration of acid can be difficult to control, and penetration through the dermis can result in slow-healing ulcerations and scar formation. Pain also can be a problem with this therapy.
• Response rates are between 50–81%, and there is a high rate of recurrence.

Mechanical Excision

• Shave biopsy removal of external genital warts by scissors or scalpel excision can be a simple, effective treatment. It may also produce tissue for the pathologic study. Scissors are especially effective for isolated pedunculated lesions.
• The cosmetic results are usually good, and the wound requires no sutures. Mechanical excisions should be performed at the middle level of the dermis. The goal is to not penetrate too deeply to avoid scarring. If penetration occurs to the level of fatty tissue, convert the area to a fusiform excision and close with sutures.

• Elimination of obvious, symptomatic, or troublesome external genital warts
• Debulking HPV lesions before vaginal delivery to prevent bleeding and tearing of vaginal or perineal tissues

Contraindications and Precautions

• Imiquimod is not indicated for use on occluded mucous membranes, the uterine cervix, or in children.
• Imiquimod may damage condoms or diaphragms.
• Podofilox is not recommended for use in the vagina, urethra, perianal area, or cervix. It has not been studied for pregnancy, but its parent compound is contraindicated in pregnancy.
• LEEP is not recommended for penile, vaginal, and anal verge lesions.
• TCA and BCA are not recommended for use in vagina, cervix, or urinary meatus.

• Apply imiquimod cream to external genital warts 3 times each week every other day for up to 16 wks. It should be rubbed into the lesion to increase absorption. Cream may be applied to affected area, not exclusively to the lesion.
• Apply podofilox solution with applicator or toothpick bid for 3 consecutive days, with 4 consecutive days of no therapy each week, for a maximum 4 wks (Fig. 41-1).
• Thin layer of TCA or BCA solution is applied only to the wart itself. If desired, normal or surrounding skin may be protected with petroleum jelly, but it is unnecessary if care is used in application of the acid. Bicarbonate, talc, or soap and water may be used to neutralize any excess acid. A 50% TCA solution is applied with a cotton-tipped applicator or toothpick to the affected area 3 times each week for a maximum of 4 wks (most commonly used regimen), or an 80% solution can be applied bid for 3 consecutive days each week for a maximum of 4 wks.
• To remove the lesion with LEEP, first inject an anesthetic under the site.
  • With the operator's hand resting against the patient for stability, a medium-sized loop or "square'' loop is introduced just above the base of the lesion and pulled completely through to debulk it (Fig. 41-2).
  • The remaining lesion should be carefully shaved down to the dermis using the side of the loop and fine "paint-brush'' or feathering strokes (Fig. 41-3). Fulguration can be used for hemostasis, but it is usually unnecessary. A bulk specimen may then be sent for histologic study if desired.
  • Pitfall: Care should be taken to not penetrate dermis during shave excision. A proper shave site has gently sloping sides, dermis at the base, and no subcutaneous fat showing through.
• In cryotherapy, large, cotton-tipped applicators for liquid nitrogen are easy to use and require little skill.
  • If using a standard long-handled, cotton-tipped applicator, increase the size of the cotton head by pulling wisps of cotton off of a cotton ball and loosely rolling them onto the applicator.
  • Dip the applicator into liquid nitrogen for 5–10 secs, and then place it on the lesion until a 2-mm ice ball forms beyond edges of lesion (Fig. 41-4). Repeat application once the ice ball thaws.
  • Therapy is repeated at 2-wk intervals until the lesion resolves. Cryounits using NO₂ may also be used (see Chap. 19, Skin Cryosurgery and Chap. 38, Cryotherapy for the Uterine Cervix).
• Before mechanical excision, wipe the area to be shaved with alcohol, and allow it to dry. Inject anesthetic just beneath lesion to raise wheal (Fig. 41-5).
  • Stabilize the area using a thumb and index finger. Using a no. 15 blade, shave the lesion flush with the level of normal tissue (Fig. 41-6). Hold blade nearly parallel to surrounding skin. Place tissue in formalin, and send it for pathologic analysis. Apply Monsel's solution (i.e., ferric subsulfate), pressure, or cautery to stop bleeding.
  • Alternatively, scissors may be used to remove lesions. With jaws of scissors partially closed, bring the smallest point of the opening up against the base of the lesion. As soon as scissors start cutting skin, gently lift the lesion upward with the blades of scissors as you are cutting. This keeps the cut in a shallow plane that prevents formation of a deep crater.
  • Pitfall: Take care to not penetrate dermis during shave excision, because this can induce scarring.

In addition to the codes in the following chart, you may also consider using benign excision from the genitalia codes (11420–11426) or malignant excision from the genitalia codes (11620–11626), depending on pathology findings.

CPT is a trademark of the American Medical Association.