Condylomata acuminata (anogenital warts) in children

INTRODUCTION — Condylomata acuminata (also known as anogenital warts or venereal warts) are manifestations of human papillomavirus (HPV) infection that typically appear as flesh-colored or hyperpigmented verrucous papules or plaques in the perianal or genital region. Condyloma acuminatum may develop as a result of the acquisition of HPV infection via sexual or nonsexual means. In very young children, transmission of HPV via nonsexual contact may be the most common precipitator of these lesions.

The transmission, diagnosis, and management of condyloma acuminatum in children will be discussed here. Condyloma acuminatum in adults and cutaneous warts 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): Management of external condylomata acuminata in adult males" and "Cutaneous warts (common, plantar, and flat warts)".)

EPIDEMIOLOGY — Epidemiologic data on condyloma acuminatum in children are limited, and the prevalence of this condition in infants and children is unknown. Estimates of the average age at which children present with condyloma acuminatum range between 2.8 and 5.6 years [1]. A female predominance is suggested by several studies [2-4].

ETIOLOGY — Condyloma acuminatum is caused by infection with human papillomavirus (HPV), a double-stranded DNA virus with more than 100 serotypes [2]. Although condyloma acuminatum in adults is commonly caused by HPV 6 and 11, the HPV types detected in lesions from children are more variable. HPV types associated with cutaneous warts (eg, HPV 1 to 4 and others) are frequently detected in anogenital lesions from children [2,5]. In one review of approximately 200 pediatric cases of condylomata acuminata in which HPV DNA was detected, HPV 6 or 11 was detected in 56 percent, HPV 1 to 4 in 12 percent, and HPV 16 or 18 in 4 percent [5]. A separate series in which 40 children under the age of 12 with condyloma acuminatum underwent wart excision and HPV testing found that HPV types 6, 11, and/or 16 were present in only one-third of cases [2]. (See "Human papillomavirus infections: Epidemiology and disease associations".)

TRANSMISSION — The possibility of sexual abuse is a major concern in the evaluation of children with condyloma acuminatum. However, other modes of viral transmission may account for the majority of pediatric cases [6]. The potential methods for human papillomavirus (HPV) acquisition in children are described below:

●Heteroinoculation – Transmission of HPV may occur during nonsexual contact with a caregiver, such as bathing or diaper changing.

●Autoinoculation – Children may acquire anogenital lesions from themselves due to transmission of HPV from other cutaneous or mucosal sites of infection.

●Sexual abuse – Estimates of the proportion of children with condyloma acuminatum who have been sexually abused vary widely, ranging from <10 percent to 90 percent [4,6].

The likelihood of sexual abuse as the cause of HPV infection increases as children age [2,6,7]. In a retrospective study of 55 children under the age of 13 with condyloma acuminatum who were evaluated for sexual abuse, children between the ages of four and eight years were 2.9 times more likely than children under the age of four years to have been sexually abused (95% CI 0.7-12.4) [6]. In addition, children between the ages of 8 and 12 were 12.1 times more likely than the youngest group of children to have been sexually abused (95% CI 2.3-63.6).

●Perinatal or prenatal transmission – HPV infection in newborn infants may occur during vaginal delivery through an infected maternal genital tract. In addition, HPV DNA has been detected in amniotic fluid and umbilical cord blood, suggesting that ascension of the infection into the uterus and hematogenous dissemination of the virus may be routes of prenatal HPV transmission [8,9]. A report of perianal warts in a neonate supports the possibility of prenatal HPV transmission [10].

●Transmission via fomites – Transmission of HPV via fomites, such as contaminated towels or underwear, has been proposed as a method of HPV infection [1,11]. However, fomites are likely to account for very few cases of condyloma acuminatum in children.

The identification of the route of virus acquisition in children with condyloma acuminatum is complicated by the variable incubation period of HPV. Data in adults indicate that a typical incubation period ranges from three weeks to eight months [11]. The average duration of the incubation period is three months [11].

In addition, serotyping is not a reliable method for determining the mode of HPV acquisition in children. The detection of a primarily cutaneous subtype of HPV is insufficient to rule out sexual abuse. As an example, cutaneous HPV infection on the hand of a sexual perpetrator could be transmitted to the anogenital region of a child through manual-genital abuse. Moreover, the HPV serotypes most commonly associated with sexually transmitted condyloma acuminatum in adults (eg, HPV 6 and 11) are detected with variable frequency in condyloma acuminatum in children [2,5,7].

CLINICAL MANIFESTATIONS — Condylomata acuminata initially appear as flesh-colored, pink, or brown soft moist papules that are a few millimeters in diameter (picture 1A-B). Over the course of weeks to months, the papules may coalesce into larger plaques that often demonstrate a "cauliflower appearance" (picture 2). In boys, condylomata acuminata are most commonly detected in the perianal area and are less frequently found on the penile shaft. Girls may present with lesions on the perianal area, vulva, hymen, vaginal vestibule, and/or periurethral areas. Anogenital warts may also occur on the internal mucosal surfaces of vagina or rectum.

Although occasional lesions are pruritic or painful, condyloma acuminatum is usually asymptomatic. Rarely, bleeding occurs.

CLINICAL COURSE — Few data are available on the natural history of condyloma acuminatum in children, but there is evidence that many infections resolve spontaneously within a few years. In a retrospective and prospective study of 41 children with condyloma acuminatum, spontaneous resolution occurred within five years in six of eight children who never received treatment [3]. The average duration of these lesions prior to resolution was nine months (range 5 to 12 months). Among the 33 children who were treated, 9 (27 percent) had resolution that appeared attributable to treatment and 16 (48 percent) had resolution that appeared to be spontaneous (the disappearance of condylomata acuminata failed to correlate with the timing of treatment). The average duration of lesions in the group with apparent spontaneous resolution was 25 months (range 2 to 58 months).

Similar to many other infections, immunosuppression influences the course and prognosis of condyloma acuminatum. Immunosuppressed children may develop extensive lesions that are challenging to treat [12].

DIAGNOSIS AND EVALUATION — The diagnosis of condyloma acuminatum is usually made via clinical examination. Biopsies are rarely required, and are usually reserved for patients in whom the diagnosis is uncertain or when the warts demonstrate atypical features, such as ulceration. Common histopathologic features of condyloma acuminatum include [13]:

●Marked acanthosis with some papillomatosis and hyperkeratosis

●Vacuolated koilocytes (less prominent than other viral warts)

●Coarse keratohyaline granules

Viral serotyping can be performed by polymerase chain reaction (PCR) or nucleic acid hybridization assays [14]. However, viral serotyping is not routinely performed since it is not necessary for diagnosis and is not reliable for identifying the source of infection. (See 'Transmission' above.)

Assessment for sexual abuse — Although it is likely that many children with condyloma acuminatum acquire the disorder through nonsexual means, the possibility of sexual abuse warrants serious consideration during patient evaluation. Children under four years of age with condyloma acuminatum are less likely to be victims of sexual abuse than older children, but the possibility of sexual abuse cannot be definitively excluded based upon age. (See 'Transmission' above.)

Interviews with the caregivers and the child (if old enough to participate), as well as clinical or laboratory examination to evaluate for sexual abuse and other sexually transmitted infections are important components of the patient assessment. If any findings suggestive of sexual abuse are detected, reporting to child protective services or legal authorities in accordance with local policies is indicated.

Due to the greater likelihood of sexual abuse as a precipitator of condyloma acuminatum in older children, a higher level of suspicion should exist for children over the age of four [1]. Exceptions include adolescents who report consensual sexual activity and immunosuppressed children with multiple nongenital warts who lack other findings suggestive of abuse.

We agree with the following approach to the initial evaluation for sexual abuse in children with condyloma acuminatum [1]:

●Interview of primary caregivers to determine whether the child may be at risk for sexual abuse and to establish the presence of cutaneous or anogenital warts in the caregivers or other family members

●Interview of the child regarding sexual abuse by a professional trained in this field (provided the child is old enough to participate - usually three to four years of age)

●Assessment for signs or symptoms that may accompany a history of sexual abuse (eg, nightmares, advanced sexual knowledge, sexual behavior with peers)

●Physical examination for evidence of physical or sexual abuse, including magnified examination of genital and anal sites looking for signs of acute trauma (hymenal bruising, petechiae, anal tears) or chronic trauma (absent hymen at the posterior hymenal rim, anogenital scarring)

●Screening for other sexually transmitted diseases as determined appropriate by the scenario (eg, gonorrhea, chlamydia, trichomoniasis, human immunodeficiency virus, hepatitis B and C, syphilis)

●Referral to a child abuse specialist if the clinicians involved are not comfortable or adequately trained to perform this assessment

The evaluation and reporting of sexual abuse in children is discussed in greater detail separately. (See "Evaluation of sexual abuse in children and adolescents" and "Child abuse: Social and medicolegal issues".)

DIFFERENTIAL DIAGNOSIS — Condylomata acuminata share clinical features with several disorders. Examples of disorders to consider in the differential diagnosis are provided below:

●Molluscum contagiosum – Molluscum contagiosum is a cutaneous viral infection commonly seen in children. The recognition of round, smooth, skin-colored papules with central umbilication supports a diagnosis of molluscum contagiosum (picture 3). (See "Molluscum contagiosum".)

●Pyramidal perianal papules – Pyramidal perianal papules (infantile perianal pyramidal protrusions) are solitary, fleshy perianal protrusions that occur in prepubertal children (picture 4). These lesions are found anterior to the anus and are less than 2 cm in diameter. Female children are most frequently affected. Pyramidal perianal papules usually resolve spontaneously with time. (See "The pediatric physical examination: The perineum", section on 'Anus and rectum'.)

●Condylomata lata of syphilis – Condylomata lata of secondary syphilis are highly infectious, moist papules and small plaques that may develop in the anogenital region (picture 5). Serologic testing is useful for diagnosis. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Clinical manifestations' and "Syphilis: Screening and diagnostic testing".)

●Epidermal nevi – Epidermal nevi are uncommon skin lesions that present at birth or in early childhood as skin-colored to hyperpigmented verrucous plaques (picture 6). A linear distribution or a distribution that follows Blaschko's lines (figure 1) is suggestive of an epidermal nevus.

TREATMENT — Multiple therapies have been utilized for the treatment of condyloma acuminatum in children and adults. The therapeutic options consist of interventions that mechanically or chemically destroy infected tissue or that upregulate the host immune response against infected cells.

Since many cases of condyloma acuminatum in children resolve spontaneously within a few years [3,14] and the response to treatment is variable, treatment of condyloma acuminatum is optional. Nonintervention with a "wait and see" approach is frequently utilized for the management of condyloma acuminatum in children [1,4]. Treatment is preferred over nonintervention when patients develop symptoms (eg, pruritus, bleeding, or pain) [1] or when concern over the appearance of lesions causes emotional distress in the child or is socially detrimental. In addition, warts that persist for more than two years may be less likely to resolve spontaneously than younger lesions [3]. (See 'Clinical course' above.)

Therapeutic options — Multiple therapies (eg, topical cytotoxic agents, topical and systemic immune modulators, cryotherapy, electrocauterization, electrodesiccation and curettage, lasers, and surgery) have been utilized for the treatment of condyloma acuminatum. However, no single treatment is consistently effective and lesion recurrence often occurs [1]. (See "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males".)

The ability of the child to tolerate treatment strongly influences treatment selection. Young children are often fearful of painful treatments such as cryotherapy, and local or general anesthesia is typically required for surgical and ablative laser therapy. Thus, topical therapy is frequently utilized as the initial treatment for condyloma acuminatum in children.

The most common topical agents utilized for pediatric condyloma acuminatum are imiquimod and podophyllotoxin. Data on the efficacy and safety of these and other therapies for condyloma acuminatum in children are limited. In a randomized trial of 45 adults with condyloma acuminatum that directly compared imiquimod 5% cream (three times per week for up to 16 weeks) and podophyllotoxin 0.5% solution (three days per week for up to four weeks), the efficacy of these agents was similar [15]. Surgical and laser therapy are typically reserved for children with large or recalcitrant lesions.

Imiquimod — Imiquimod 5% cream and a newer formulation, imiquimod 3.75% cream, are topical immune response modifiers for which randomized trials have demonstrated efficacy for the treatment of external genital and perianal warts [16-18]. Imiquimod 5% cream is applied three times weekly on nonconsecutive days for a maximum of 16 weeks. The 3.75% formulation is applied once daily for up to eight weeks. (See "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males", section on 'Imiquimod'.)

Data are limited on the safety and efficacy of imiquimod in children under the age of 12 years. The use of imiquimod in children is supported by several case reports [19-23] and a retrospective study in which eight children with anogenital warts (six under the age of five years) were treated with imiquimod three times per week for two to four months [24]. Six children (75 percent) in the retrospective study had clearance of warts that persisted for at least 6 to 12 months.

The most common side effect of topical imiquimod is local skin irritation. In our experience, this occurs most frequently at sites of skin occlusion. Infrequently, flu-like symptoms may occur during treatment.

Podophyllotoxin — Podophyllotoxin is an antimitotic agent that is effective for the treatment of condyloma acuminatum [25-27]. Podophyllotoxin is commercially available as podofilox 0.5% solution and gel (typically applied twice daily for three consecutive days per week for up to four weeks) and as podophyllin 25% liquid, which must be applied in the office by a clinician. (See "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males", section on 'Podophyllotoxin'.)

Although the efficacy of podophyllotoxin for condyloma acuminatum is supported by randomized trials performed in adults [15,27-30], data on the efficacy and safety of podophyllotoxin in children are limited. In a retrospective study of 17 children with condyloma acuminatum, including 11 children who were under the age of five years, treatment with podofilox 0.5% gel for one to four months (initially once weekly and increased as tolerated to twice daily for three consecutive days per week) led to clearance of lesions for at least four months in 88 percent of children [24]. One child failed to respond to treatment and a second child was unable to tolerate therapy.

The comparative efficacy of podophyllotoxin 0.5% and podophyllin 25% was evaluated in a randomized trial of 358 adults that compared treatment with podophyllotoxin 0.5% solution, podophyllotoxin 0.15% cream, and podophyllin 25% liquid [27]. Podophyllotoxin 0.5% solution was more effective than podophyllin 25% liquid for the clearance of all warts (84 versus 62 percent of patients had clearance of lesions). Relapse was common after the discontinuation of all treatments.

Local skin irritation, discomfort, and ulceration are potential adverse effects of podophyllin therapy. Relapse is common after the discontinuation of treatment [27].

Surgical and laser therapy — Surgical and laser procedures are usually reserved for children with extensive or large warts (eg, 1 cm or greater) or warts recalcitrant to topical therapy. Options for surgical treatment include cryotherapy, electrodesiccation, carbon dioxide laser ablation, and surgical debulking or excision. Clearance of childhood perianal warts has also been reported after treatment with a pulsed dye laser [31].

Similar to medical therapy, warts may recur after destructive procedures. Additional information on these procedures is reviewed separately. (See "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males", section on 'Surgical excision'.)

Other — Multiple other treatments have been utilized for the treatment of condyloma acuminatum in adults, including trichloroacetic acid, fluorouracil, sinecatechins, topical cidofovir, cimetidine [32,33], cantharidin, and additional agents. Routine use of cantharidin in the genital region is not recommended because of concern for the development of severe blistering reactions [34]. The efficacy and safety of these treatments in children has not been established. These treatments are reviewed in greater detail separately. (See "Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in adult males".)

FOLLOW-UP — Although human papillomavirus (HPV) infection has been associated with increased risk for cervical, anal, and penile cancer, the impact of childhood HPV infection on the risk for these malignancies is unknown (table 1) [11,35,36]. (See "Virology of human papillomavirus infections and the link to cancer" and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Risk factors' and "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Pathogenesis' and "Clinical features and staging of anal cancer", section on 'Clinical features' and "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Clinical manifestations, diagnosis, and evaluation'.)

Long-term, periodic follow-up for signs or symptoms of anal cancer is recommended for children with anogenital warts that extend beyond the anal verge and involve the mucosa. (See "Clinical features and staging of anal cancer", section on 'Clinical features' and "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment", section on 'Clinical manifestations, diagnosis, and evaluation'.)

PREVENTION — Avoidance of autoinoculation or heteroinoculation of human papillomavirus (HPV) into the anogenital region is the primary mode of prevention of condyloma acuminatum. HPV vaccination that protects against the HPV types that cause condylomata acuminata is discussed in greater detail separately. (See "Human papillomavirus vaccination".)

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".)

SUMMARY AND RECOMMENDATIONS

●Condylomata acuminata (also known as anogenital warts or venereal warts) are cutaneous lesions caused by infection with human papillomavirus (HPV). Both mucosal and cutaneous HPV serotypes can lead to the development of condyloma acuminatum in children. (See 'Etiology' above.)

●Condyloma acuminatum in children may arise from HPV transmission through a variety of mechanisms. Although the possibility of sexual abuse is a major concern, many children, particularly those under the age of four years, acquire HPV infection through nonsexual interactions. (See 'Transmission' above.)

●Condyloma acuminatum usually begins as single or multiple flesh-colored, pink, or brown papules (picture 1A-B). As the infection progresses, lesions may develop into large verrucous plaques with a "cauliflower-like" appearance (picture 2). (See 'Clinical manifestations' above.)

●Spontaneous resolution of condyloma acuminatum is possible, and many infections resolve within a few years. Lesions that persist for more than two years or develop in immunosuppressed individuals may be less likely to resolve without treatment. (See 'Clinical course' above.)

●The possibility of sexual abuse should be considered in all children who present with condyloma acuminatum. Children over the age of four years are more likely to have a history of sexual abuse than younger children. The evaluation for sexual abuse typically begins with interviews with the caregivers and child, a complete physical examination, and screening for other sexually transmitted diseases. (See 'Assessment for sexual abuse' above and "Evaluation of sexual abuse in children and adolescents".)

●Treatment is optional for children with condylomata acuminata since lesions may resolve spontaneously. Warts that persist for longer than two years may be less likely than younger lesions to resolve without treatment. (See 'Treatment' above.)

●Since most condylomata acuminata in children resolve within a few years, treatment is not required for most children with asymptomatic lesions. For children with symptomatic lesions, lesions that fail to spontaneously resolve, immunosuppression, or lesions that lead to emotional distress or social problems, we suggest treatment with imiquimod 5% or 3.75% cream or podophyllotoxin 0.5% gel or solution (Grade 2B). Children with lesions recalcitrant to topical therapy may benefit from laser therapy or surgical procedures. (See 'Therapeutic options' above.)