Version May 2024
INTRODUCTION — Condylomata acuminata (CA), also known as anogenital warts, are manifestations of anogenital human papillomavirus (HPV) infection. CA manifest as variably sized and shaped soft papules or plaques on anogenital skin (picture 1A-H).
A diagnosis of CA can have negative psychosocial effects and may be accompanied by symptoms, such as pruritus, pain, and bleeding. Some cases of CA spontaneously resolve; however, spontaneous resolution is unpredictable. Most patients desire treatment.
Effective treatment options for CA include patient-applied and clinician-administered therapies. First-line patient-applied therapies include imiquimod, podophyllotoxin, and sinecatechins. First-line clinician-administered treatments are cryotherapy, trichloroacetic acid (TCA) and bichloroacetic acid (BCA), surgical excision, electrosurgery, and laser therapy. The selection of therapy should be individualized and based upon consideration of the extent of disease, patient preference, cost, adverse effects, treatment availability, and the response to previous treatments.
The management of external CA in adolescent and adult males will be reviewed here. The diagnosis of CA, the management of vulvar or vaginal CA, and CA in children are reviewed separately. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis" and "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts" and "Condylomata acuminata (anogenital warts) in children".)
PATIENT COUNSELING — A diagnosis of CA is often distressing and associated with concerns regarding cosmetic appearance, stigmatization, personal health, and sexual relationships. Educating patients about human papillomavirus (HPV) infection and CA is an important component of management. Patients may benefit from the following information:
●HPV is a common viral infection that manifests in some patients as anogenital warts. HPV infection is acquired through direct genital contact. Most people acquire HPV infection at some point during their lifetime. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis".)
●Infection may be acquired weeks to many months prior to the appearance of anogenital warts. The timing of infection cannot be confirmed. Therefore, the appearance of anogenital warts does not guarantee infidelity within a current sexual relationship. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Transmission'.)
●Patients with anogenital warts may be at risk for other sexually transmitted diseases. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Other sexually transmitted diseases'.)
●Individuals with anogenital warts can transmit HPV to sexual partners. Patients should inform current sexual partners of their diagnosis. Sexual partners may benefit from an evaluation for anogenital warts and other sexually transmitted diseases [1].
●There are a variety of effective treatments for anogenital warts. Without treatment, anogenital warts may spontaneously resolve, persist, or progress. It is estimated that approximately one-third of anogenital warts regress without treatment within four months [2,3]. It is not possible to predict which anogenital warts will resolve without treatment [4,5].
●HPV infection can remain after successful removal of anogenital warts and may be transmitted to other individuals even if warts are no longer visible. It is unclear whether eradicating anogenital warts decreases future transmission of HPV. Condom use may help to reduce acquisition of anogenital warts [6]; however, HPV infection may still be transmitted through contact with infected skin that is not covered by a condom.
The negative impact of anogenital warts on psychosocial well-being has been demonstrated in multiple studies [7-9]. Clinicians should offer resources for psychologic support when needed.
Disclosure of sexually transmitted infections to sexual partners may have beneficial psychologic effects. In a survey study of 117 individuals with genital herpes, 82 individuals with HPV, and 75 individuals without sexually transmitted infection, persons who disclosed that they had a sexually transmitted infection had significantly more positive feelings about aspects of their sexual self-concept than those who had not disclosed their sexually transmitted infection [10].
Additional resources for patient information are provided. (See 'Information for patients' below.)
EVALUATION FOR INTERNAL INVOLVEMENT — Patients with external CA may have associated involvement of the urethra or anal canal. Indications for evaluating these sites are reviewed separately. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Internal involvement'.)
INDICATIONS FOR TREATMENT — All patients should be offered treatment. While anogenital warts may spontaneously resolve, they also may spread or enlarge, making treatment more difficult. Therefore, deferring treatment is not recommended. Given the uncertainty regarding resolution and the negative psychosocial and physical effects of anogenital warts (eg, pruritus, pain, bleeding, interference with micturition, defecation, and sexual function), most patients desire treatment. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Clinical course'.)
TREATMENT OPTIONS — Treatment options for external CA include patient-applied topical medications and clinician-administered treatments [1].
First-line patient-applied therapies include:
First-line clinician-administered therapies include:
●Cryotherapy
●Trichloroacetic acid (TCA) and bichloroacetic acid (BCA)
●Surgical removal (excision, electrosurgery, or laser)
The mechanisms of action of these interventions include antiproliferative properties (podophyllotoxin), immunomodulatory effects (imiquimod and sinecatechins), and ablative/destructive effects (cryotherapy, TCA, surgical excision, electrosurgery, and laser).
Other therapies are less commonly used for CA or reserved for refractory disease because of limited evidence for efficacy or safety concerns. (See 'Other therapies' below and 'Refractory disease' below.)
TREATMENT SELECTION
General approach — The selection of a first-line treatment for external CA should be individualized and directed by factors such as the number, size, and location of warts; patient preference; cost considerations; adverse effects; clinician skill; and treatment availability. No single therapy has emerged as the standard of care (see 'First-line patient-applied therapies' below and 'First-line clinician-applied therapies' below):
●Size of anogenital warts – Although patients with single or multiple small (eg, <1 cm) anogenital warts may be effectively treated with any of the patient-administered or clinician-administered first-line treatments, clinician-administered destructive therapies are often favored given the rapid results compared with long-term topical therapy. Cryotherapy is a typical first-line treatment given that it is a widely available, well-tolerated therapy that is easy to administer and does not require anesthesia. Electrosurgery is an additional favored option for the treatment of small genital warts; however, electrosurgery may result in more scarring than cryotherapy. Both cryotherapy and electrosurgery may result in local skin dyschromia; the risk is greatest in patients with moderately to darkly pigmented skin.
Extensive disease (eg, large exophytic plaques or nodules (picture 2)) may be best managed with surgical excision, laser ablation, or electrosurgery. Topical agents are commonly used as adjunctive therapy for remaining disease [11].
●Patient preference – Patients may express a preference for patient-applied versus clinician-applied treatments. Some patients prefer to treat CA privately at home, whereas others prefer to avoid the prolonged treatment courses associated with patient-applied therapies and prefer the rapid results of clinician-administered ablative treatments.
Of note, patients with visual, cognitive, or physical impairments that limit their ability to identify, treat, and reach all warts are not good candidates for patient-applied treatments.
●Cost – The cost of topical therapies is prohibitive for some patients. Of the first-line patient-applied therapies, podophyllotoxin is the least expensive. United States pricing information is available in the drug information content available with UpToDate.
●Adverse effects – Potential adverse effects of treatments should be reviewed with patients. Local inflammatory reactions are common side effects of podophyllotoxin, imiquimod, and sinecatechins. Systemic side effects can occur from treatment with imiquimod, podophyllin resin, or intralesional interferon injections. Clinician-administered ablative therapies can result in scarring and dyspigmentation.
Treatment-specific side effects are discussed in greater detail in the sections on specific therapies. (See 'First-line patient-applied therapies' below and 'First-line clinician-applied therapies' below and 'Other therapies' below.)
●Clinician skill and treatment availability – Procedures such as cryotherapy, surgical excision, electrosurgery, and laser therapy require clinicians trained to perform the procedure and appropriate equipment.
Combination therapy — Combinations of patient-applied and clinician-administered therapies are often used in clinical practice (eg, use of a patient-applied topical therapy in-between sessions of clinician-administered treatment) in an attempt to augment the response to treatment [11-15]. However, data on the efficacy and safety of this approach are limited. A randomized trial that compared cryotherapy alone with cryotherapy followed by treatment with sinecatechins ointment in 42 patients with anogenital warts found a greater reduction in the number of anogenital warts with combination therapy [13]. In contrast, a randomized trial that compared cryotherapy plus podophyllotoxin with cryotherapy alone in 140 patients with anogenital warts did not find a statistically significant difference in rates of clearance [14]. (See 'Second-line therapy' below.)
Immunosuppressed patients — The approach to treatment in immunocompromised patients does not differ from the approach for immunocompetent patients [1]. However, wart treatment is less successful in immunocompromised patients. Longer treatment courses and closer follow-up may be necessary.
FIRST-LINE PATIENT-APPLIED THERAPIES — First-line patient-applied therapies include imiquimod, podophyllotoxin, and sinecatechins [1,16].
Imiquimod — Imiquimod is an immunomodulatory drug that increases the immune response to warts [17]. Imiquimod is a powerful cytokine inducer that stimulates production of interferon-alpha, tumor necrosis factor, and interleukin (IL) 1, IL-6, and IL-8. Imiquimod 5% cream and 3.75% cream are used for the treatment of anogenital warts:
●Efficacy – A systematic review of randomized trials found imiquimod superior to placebo for achieving complete and partial regression of anogenital warts (relative risks 4.03, 95% CI 2.03-7.99 and 2.56, 95% CI 2.05-3.20, respectively) but did not identify superiority for recurrence rates or new wart development [18]. The quality of evidence for outcomes assessed in the review was low to very low due to risk of bias, imprecision, and inconsistency. Clearance rates from randomized trials for imiquimod 5% cream range from 35 to 75 percent [19,20]. Recurrence rates range from 6 to 26 percent [19].
Efficacy of the 3.75% concentration of imiquimod also has been demonstrated in randomized trials [21-23]. In two identical, phase 3, placebo-controlled, randomized trials, 447 adolescent and adult males with anogenital warts were randomly assigned in a 2:2:1 ratio to self-treatment with imiquimod 3.75% cream, imiquimod 2.5% cream, or placebo once daily until complete clearance or a maximum of eight weeks [22]. Patients who did not achieve complete clearance by eight weeks were followed for clearance for up to an additional eight weeks (end of study). At end of study, the complete clearance rates with imiquimod 3.75% (20 and 17 percent) were superior to placebo in both trials. The complete clearance rates for imiquimod 2.5% cream (13 and 15 percent) were superior to placebo only in the second trial.
Although reported cure rates for imiquimod 5% cream appear higher than those for imiquimod 3.75% cream, the efficacy of these agents has not been directly compared and methodologic differences between studies may contribute to the disparity. An advantage of the 3.75% formulation is the shorter treatment duration.
●Administration – Patients should apply imiquimod 5% cream to anogenital warts three times per week (eg, Monday, Wednesday, Friday) until there is total clearance of the anogenital warts or for a maximum of 16 weeks. A thin layer of imiquimod 5% cream should be applied to each wart and rubbed in until the cream is no longer visible. Imiquimod 5% cream should be applied prior to normal sleeping hours and left on the skin for 6 to 10 hours, after which the cream should be removed by washing the area with mild soap and water. The prescriber should demonstrate the proper application technique (including clear directions for the locations to treat and amount of medication to apply) to maximize benefit [24].
A different regimen is used for imiquimod 3.75% cream. Patients should apply a thin layer of imiquimod 3.75% cream to anogenital warts once daily for eight weeks. The cream should be applied prior to normal sleeping hours and washed off after eight hours with mild soap and water [21].
●Adverse effects – Local inflammatory reactions, including redness, irritation, induration, ulceration, erosions, and vesicles, are common with the use of imiquimod 5% cream. A rest period of several days may be taken, if necessary, because of patient discomfort or severity of the reaction. Treatment may resume once the reaction subsides. Nonocclusive dressings (eg, cotton gauze or cotton underwear) may be used in the management of skin reactions.
In addition, hypopigmentation may develop at the site of treatment. Flu-like symptoms occur infrequently. Rare cases of vitiligo [25-27] and reversible penile curvature secondary to edema [28] have been reported in association with imiquimod treatment.
Imiquimod can weaken condoms and vaginal diaphragms [29]. Sexual contact should be avoided while imiquimod is on the skin [21].
Podophyllotoxin — Podophyllotoxin is an antimitotic drug that can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum). In the United States, podophyllotoxin is available as a 0.5% solution or gel. In other locales, podophyllotoxin may also be available as a 0.15% cream:
●Efficacy – Placebo-controlled randomized trials support the efficacy of podophyllotoxin for CA [30-33]. A systematic review of randomized controlled trials found clearance rates from 45 to 83 percent with use of podophyllotoxin 0.5% solution for three to six weeks and 43 to 70 percent with use of podophyllotoxin 0.15% cream for four weeks [19]. Recurrence rates range between 13 and 100 percent [19]; differences in the criteria used to assess relapse and follow-up intervals may contribute to the wide variation.
●Administration – Patients should apply podophyllotoxin twice daily for three consecutive days, then withhold use for four consecutive days. This one-week course may be repeated up to four times until warts are no longer visible.
The total treatment area should not exceed 10 cm2, and the total volume of podophyllotoxin should be limited to 0.5 mL per day. The area to which podophyllotoxin is applied should not contain any open lesions or wounds. Podophyllotoxin should be washed off one to four hours after application in order to minimize local irritation. If feasible, the clinician should apply the first treatment to demonstrate the correct sites for application and proper technique [1]. Sexual intercourse should be avoided when podophyllotoxin is on the skin.
●Adverse effects – In clinical trials of podophyllotoxin 0.5% solution or gel, local adverse effects were primarily mild or moderate and did not increase during the treatment period. Severe reactions most often occurred during the first two weeks of treatment. Common adverse effects include local pain, inflammation, erosions, burning, or itching. Excessive application may contribute to adverse effects [34]. The most common systemic adverse effect reported during the clinical studies was headache (7 percent).
Sinecatechins — Sinecatechins ointment is a partially purified fraction of the water extract of green tea leaves from Camellia sinensis and consists of a proprietary mixture of catechins and other green tea components [35]. Sinecatechins ointment is available in 10% and 15% formulations. Only the 15% ointment is available in the United States.
The mechanism of action of sinecatechins on anogenital warts is not fully understood. Sinecatechins have been found to upregulate apoptosis-associated genes and to modulate and downregulate genes involved in the proinflammatory response to human papillomavirus (HPV) infection [36,37]. They are also antiproliferative, antiangiogenic, and, most importantly, directly antiviral [38]:
●Efficacy – Efficacy of sinecatechins for anogenital warts is supported by randomized trials [35,39-41]. An analysis of combined data from two identical, phase 3, placebo-controlled, randomized trials in which a total of 1005 adults with anogenital warts were randomly assigned to apply sinecatechins 15% ointment, sinecatechins 10% ointment, or placebo three times daily until complete clearance or for up to a maximum of 16 weeks found that 55, 54, and 35 percent of patients, respectively, achieved complete clearance of all warts during treatment [35]. When males were analyzed separately, complete clearance rates were 49, 46, and 29 percent, respectively. Recurrence rates after complete clearance were low during a 12-week follow-up period, occurring in 7 percent of patients in both sinecatechins treatment groups and 6 percent of patients in the placebo group.
●Administration – Sinecatechins 10% and 15% ointments are applied three times per day to anogenital warts until complete clearance, for up to a maximum of 16 weeks. Patients should apply an approximately 0.5 cm strand of the ointment to each wart using fingers. The ointment should be dabbed onto warts to ensure complete coverage, leaving a thin layer of the ointment on the warts [42]. Patients should wash their hands before and after application. It is not necessary to wash off the ointment prior to the next treatment.
Sinecatechins ointment may weaken condoms and diaphragms. Sexual contact should be avoided when the ointment is on the skin [42].
●Adverse effects – Local skin reactions (eg, erythema) at the treatment site are frequent [39,41]. Treatment should be continued when the severity of the local skin reaction is acceptable.
FIRST-LINE CLINICIAN-APPLIED THERAPIES — First-line clinician-applied therapies include cryotherapy, trichloroacetic acid (TCA) and bichloroacetic acid (BCA), excision, electrosurgery, and laser therapy [16].
Cryotherapy — Cryotherapy involves the use of liquid nitrogen to cause tissue damage by formation of ice crystals, leading to disruption of cell membranes and cell death. This treatment can be used for single or multiple anogenital warts and is most effective for small warts [43,44]. Treatment success rates from randomized trials range from 44 to 75 percent [19].
Liquid nitrogen is typically applied via a spray gun device or a cotton bud, and two freeze-thaw cycles are performed. A small margin of healthy skin (eg, 1 mm) should be included in the treatment area. We typically treat patients every two weeks for up to 6 to 10 weeks. If clearance has not been achieved within 6 to 10 weeks, other treatment should be implemented. (See "Minor dermatologic procedures", section on 'Cryotherapy (cryosurgery)'.)
Patients experience local burning and pain during cryotherapy. Potential side effects after treatment include blistering, dyspigmentation, and scarring. Hyperesthesia and hypoesthesia also can occur after cryosurgery but are almost always temporary [45]. (See "Minor dermatologic procedures", section on 'Adverse outcomes and considerations'.)
Electrosurgery — Anogenital warts can be destroyed with electrocautery [46]. After the injection of a local anesthetic, warts are desiccated and are either left to fall off or curetted. Care must be taken to control the depth of electrocautery to minimize scarring. Similar to surgical excision, high clearance rates (94 to 100 percent) have been reported in randomized trials but recurrence is possible [19]. Although these clearance rates are higher than those reported for cryotherapy, electrosurgery is more likely to result in permanent dyspigmentation and scarring.
Caution is indicated during the treatment of anal warts. Electrosurgery or excisions that injure the anal sphincter can result in anal incontinence, painful defecation, or fistulas [47].
Risk for transmission of human papillomavirus (HPV) to oral or nasal mucosa of health care workers during electrosurgery or laser treatment of anogenital warts is likely low [48]. However, it is recommended to perform electrosurgery in a well-ventilated room with exhaust ventilation at the treatment site to minimize risk of transmission [49].
Trichloroacetic acid — TCA (where available) is a relatively inexpensive caustic agent that destroys warts through chemical coagulation of protein.
TCA therapy is best suited for small warts, as its ability to penetrate skin may be limited. Clearance rates reported in randomized trials range from 56 to 81 percent [19]. TCA was less effective than cryotherapy in a trial in which 86 patients with anogenital warts were randomly assigned to once-weekly treatment with either liquid nitrogen applied with a cotton pledget or 95% TCA for up to six treatments [50]. A commercial pharmaceutical formulation of 80% TCA is no longer available in the United States or Canada.
A small amount of 80 or 90% TCA is applied directly to the warts with a cotton tip applicator and allowed to dry. A white frost becomes visible at the treatment site. A reasonable treatment course for TCA is once-weekly application for three to four weeks or every two weeks for 8 to 10 weeks.
Disadvantages of TCA include the need for multiple treatment sessions and the occurrence of a burning sensation at the site of application that lasts a few minutes. TCA should be applied carefully only to wart-bearing skin because excessive application can lead to damage to adjacent tissues. The material should be allowed to completely dry (forming a "white frost") before the patient sits up, stands, and walks.
BCA is similar to TCA and is more typically used in gynecology. Directions for use of TCA and BCA are similar. (See "Condylomata acuminata (anogenital warts): Treatment of vulvar and vaginal warts", section on 'Trichloroacetic acid and bichloracetic acid'.)
Surgical excision — Surgical excision is most beneficial for patients who have large (eg, >1 cm), exophytic anogenital warts. A scissor or shave excision can remove most anogenital warts [51]. Excision to the depth of the superficial dermis is generally sufficient [1]. More extensive excisions under general anesthesia may be required to remove extensive or bulky warts [19]. (See "Skin biopsy techniques", section on 'Shave biopsy'.)
Disadvantages of surgical excision include the need for local anesthesia and scarring at the excision site. The surgical site may be sore and tender for approximately one to four weeks. Although high success rates for excision (89 to 100 percent) have been reported in randomized trials, recurrences developed in up to one-third of patients [19].
Laser therapy — Carbon dioxide (CO2) lasers are the principal lasers used to destroy anogenital warts. Treatment is painful; local or general anesthesia is necessary. Clearance and recurrence rates after CO2 laser treatment vary widely [52]. A questionnaire-based study of 107 males treated with extensive, cauliflower-like endoanal or perianal warts found that 21 of 25 patients (84 percent) with perianal warts who responded to the questionnaire were cured after a single treatment [52]. However, only 64 patients (60 percent) responded to the questionnaire, and clearance rates as low as 23 percent and recurrence rates as high as 77 percent have been reported [53]. Potential complications include persistent pain, anal fissures, and scarring.
Other lasers are less frequently used for the treatment of anogenital warts [54]. Most reports of the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser focus on use for urethral warts [54,55]. Data on the use of the pulsed dye laser and thulium laser are limited [54,56,57]. Further study is necessary to confirm the results of an uncontrolled study that found a low rate of relapse for anogenital warts after combination treatment with a CO2 laser and one to six sessions of photodynamic therapy performed with topical aminolevulinic acid and a 635 nm laser [58].
SECOND-LINE THERAPY — Patients who do not respond to a first-line treatment may benefit from a trial of an alternative first-line treatment or combination treatment. Cryotherapy plus a topical agent is a common initial choice for combination treatment. (See 'Combination therapy' above.)
OTHER THERAPIES — Podophyllin resin and topical fluorouracil can be effective for external anogenital warts but are not recommended as first-line treatments because of side effects.
Podophyllin resin — Podophyllin is a plant-derived antimitotic agent that disrupts viral activity by inducing local tissue necrosis. Podophyllin resin is not recommended for the treatment of anogenital warts because of the availability of more efficacious and safer therapies [1].
Head-to-head studies demonstrate that podophyllin is a suboptimal treatment compared with podophyllotoxin. In a randomized trial that compared four weeks of treatment with patient-applied podophyllotoxin 0.5% solution (three consecutive days per week), patient-applied podophyllotoxin 0.15% cream (three consecutive days per week), and clinician-applied 25% podophyllin (twice weekly) for the treatment of anogenital warts, podophyllotoxin demonstrated greater efficacy and cost-effectiveness than podophyllin [59].
Common local side effects of podophyllin are application site reactions (slight stinging, pain, numbness, tingling, or burning). Podophyllin can be systemically absorbed; the toxicity of the drug increases when applied to areas greater than 110 mm2 or to skin surfaces that favor systemic absorption. Potential side effects include fever, mild gastrointestinal distress, paralytic ileus, bone-marrow suppression, polyneuritis, paresthesias, coma, and death. To minimize side effects, a thin layer of podophyllin should be applied to warts and allowed to air-dry completely. Over-application or failure to air-dry can spread the podophyllin and increase the rate of local reactions.
Topical fluorouracil — A systematic review of randomized trials found treatment with topical fluorouracil more effective than placebo or no treatment for anogenital warts in nonimmunocompromised adults (relative risk for cure 0.39, 95% CI 0.23-0.67) [60]. However, high-quality, randomized trials evaluating fluorouracil therapy are lacking, and the use of topical fluorouracil is limited by potential adverse effects, such as local inflammation, pain, burning, and ulceration.
Cantharidin — Cantharidin is a terpenoid vesicant produced by blister beetles commonly used for molluscum contagiosum and common warts. Cantharidin acts as an acantholytic blistering agent that creates a blister between the dermis and the epidermis. A trial in which 12 females with nonmucosal genital warts were randomly assigned to treatment with either trichloroacetic acid (TCA) or cantharidin found a nonstatistically significant trend favoring cantharidin treatment over TCA [61]. All six patients in the cantharidin group had complete clearance of warts versus four of six (66 percent) in the TCA group. Additional study is necessary to clarify the efficacy of cantharidin for CA.
REFRACTORY DISEASE — Patients with anogenital warts that cannot be eradicated with first-line therapies or combinations of first-line therapies may require use of alternative treatments. (See 'First-line patient-applied therapies' above and 'First-line clinician-applied therapies' above and 'Second-line therapy' above.)
There are multiple reports of positive responses of anogenital warts to topical or intralesional cidofovir, a monophosphate nucleotide analogue that competitively inhibits viral DNA polymerase [62-69]. In a phase 2, randomized trial in which 30 patients were randomly assigned to cidofovir 1% gel or placebo, 9 of 19 patients (47 percent) in the cidofovir group had a complete response compared with no patients in the placebo group [63]. In addition, cidofovir 1% cream was more effective than a vehicle cream for anogenital warts in a single-blind randomized, crossover trial with 12 human immunodeficiency virus (HIV)-infected patients [64]. In an open randomized trial, combination treatment with electrocautery and cidofovir 1% gel was more effective than monotherapy with either agent in HIV-infected patients [70]. Topical cidofovir is obtained through compounding pharmacies. Cost and insurance coverage can be limiting factors.
Intralesional interferon is infrequently used for the treatment of anogenital warts [71]. Interferon injections are expensive and most useful in combination with other treatments [72].
Rarely, systemic treatments are used for difficult cases. Benefit has been reported with low-dose oral cyclophosphamide [73,74].The mechanism of cyclophosphamide may involve selective targeting of regulatory T cells, thereby enhancing the function of human papillomavirus (HPV)-specific T cells and natural killer cells, leading to clearance of HPV infection. There are conflicting data on the efficacy of oral isotretinoin [75-78]. Treatment with systemic fluorouracil and radiation was associated with improvement in anogenital warts with associated squamous cell carcinoma in an immunosuppressed adolescent [79]. Case reports describe successful use of hyperthermia [80] and external beam radiotherapy [81] for extensive anogenital warts. There is no reliable evidence to support use of systemic interferon after ablative treatment of CA [82].
Treatment of anogenital warts with any HPV vaccine formulation cannot be recommended. Although resolution of perianal warts was reported in a patient who received the quadrivalent HPV vaccine following unsuccessful treatment with imiquimod [83], in a series of six patients vaccinated after ablation of anogenital warts with electrocautery, warts recurred in all patients [84]. (See "Human papillomavirus vaccination".)
EMERGING THERAPIES — Benefit of topical sodium nitrate with citric acid [85], Mycobacterium w vaccine [86], topical nitric-zinc complex [87], virus-like particle immunotherapy [88], glycyrrhizinic acid plus an immunostimulant food supplement [89], and photodynamic therapy [90-94] has been documented in clinical studies, and resolution of recalcitrant giant CA after combination therapy with Mycobacterium indicus pranii immunotherapy and acitretin is documented in a case report [95]. Further study is necessary prior to recommendations for the use of these treatments.
INDICATIONS FOR REFERRAL — Referral to a specialist experienced in the treatment of anogenital warts (eg, dermatologist, urologist, or colorectal surgeon) is appropriate for patients who are immunosuppressed or who have treatment-refractory anogenital warts. Patients with large, bulky perianal or genital warts that may require extensive surgical removal should be referred to a colorectal surgeon or urologist. In addition, for patients with perianal warts, we suggest performing or referring for anoscopy to evaluate for intra-anal warts. Intra-anal and intraurethral warts are typically managed by colorectal surgeons and urologists, respectively. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis", section on 'Internal involvement'.)
PROGNOSIS AND FOLLOW-UP — Recurrences may appear soon after treatment or after months or years. Factors that may contribute to recurrences after treatment include persistent subclinical infection, repeat infection, and immunosuppression.
The timing of follow-up after the start of treatment depends on the mode of treatment. For topical patient-applied therapies, patients should be re-evaluated after the completion of a treatment course. After clinician-administered destructive therapies, we typically re-examine patients after two weeks to evaluate the response and assess for proper healing.
Patients should be instructed to return for clinical evaluation if new warts develop after treatment.
PREVENTION — Sexual activity is the primary risk factor for acquisition of human papillomavirus (HPV) infection and the development of anogenital warts. The optimal way to prevent anogenital warts is vaccination prior to the onset of sexual activity. In addition, limiting the number of lifetime sexual partners and delaying the age of first intercourse reduce the risk of HPV infection [96]. Vaccination against HPV and the prevention of sexually transmitted infections are reviewed in detail separately. (See "Human papillomavirus vaccination" and "Prevention of sexually transmitted infections".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Anogenital warts (The Basics)" and "Patient education: Human papillomavirus (HPV) vaccine (The Basics)")
●Beyond the Basics topics (see "Patient education: Human papillomavirus (HPV) vaccine (Beyond the Basics)" and "Patient education: Genital warts in women (Beyond the Basics)")
Additional resources for information on HPV infection and anogenital warts include the Centers for Disease Control and Prevention (CDC) and the American Sexual Health Association (ASHA).
SUMMARY AND RECOMMENDATIONS
●Overview – Condylomata acuminata (CA), also known as anogenital warts, are a manifestation of anogenital human papillomavirus (HPV) infection (picture 1A-H). Anogenital warts are almost always acquired through sexual activity. (See "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis".)
●Patient counseling – A diagnosis of CA can have negative psychosocial effects. Patients may benefit from education on HPV infection and CA. Clinicians should offer resources for psychologic support when needed. (See 'Patient counseling' above.)
●Decision to treat – Although CA may spontaneously resolve, resolution may take months and is unpredictable. Treatment should be offered to all patients. Most patients elect to proceed with treatment. (See 'Indications for treatment' above.)
●Selection of initial treatment – There is no single best approach to the treatment of anogenital warts. Treatment selection should be individualized and based upon consideration of factors such as the extent of disease, patient preference, cost, adverse effects, and treatment availability. The major treatment options for CA can be divided into patient-applied and clinician-administered therapies (see 'Treatment options' above and 'Treatment selection' above):
•Patient-applied therapy – For patient-applied therapy, we recommend use of imiquimod, podophyllotoxin, or sinecatechins (Grade 1A). Patients treated with patient-applied therapies should be able to identify and reach all anogenital warts and should be willing to adhere to several weeks or longer of treatment. (See 'Treatment selection' above and 'First-line patient-applied therapies' above.)
•Clinician-applied therapy – First-line clinician-administered therapies include cryotherapy, trichloroacetic acid (TCA), surgical excision, electrosurgery, and carbon dioxide laser therapy. We suggest not treating anogenital warts with podophyllin resin based upon the availability of safer and more effective therapies (Grade 2C). (See 'Treatment selection' above and 'First-line clinician-applied therapies' above.)
●Failure of initial treatment – Patients who fail to respond to an initial first-line therapy may benefit from switching to an alternative first-line intervention or combination treatment. A common option for combination therapy is the use of a patient-applied topical therapy in-between treatment sessions for a clinician-administered treatment. (See 'Second-line therapy' above.)
●Prevention – Sexual activity is the primary risk factor for the development of CA. Vaccination against HPV can prevent the acquisition of CA. (See 'Prevention' above and "Human papillomavirus vaccination".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Noah Scheinfeld, MD (deceased), who contributed to an earlier version of this topic review.
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