GUIDELINES ON THE MANAGEMENT OF ANOGENITAL HPV IN CHILDHOOD

Epidemiology

As already described, HPV is the most common viral infection of the adult and adolescent female genital tract.(123-126) Although there was an increase in case reports of anogenital warts in children in the 1980s and 1990s,(127-129) serological studies suggest the population prevalence in children remains low.(130)

Clinical presentation

The prevalence of asymptomatic HPV infection of the anogenital region in children is unknown. Children usually present because a caregiver has noted the lesions, although some present with pain or bleeding on defaecation, or secondary infection. Classical cauliflower-like condyloma acuminata do occur in children, but anogenital warts have multiple appearances.(131,132) There is very little data on the prevalence of infection of the cervix or vagina in children who present with peri-anal or vulval warts.(133)

The incubation period in children is unknown. There is a high likelihood of spontaneous regression over time.(134) HPV may be particularly troublesome in children on immuno-suppressive therapy, and the possibility of immune deficiency (including HIV) should be considered in any child who has particularly refractory lesions.(135,136)

Molecular diagnosis 

In determining the source of infection, the virology adds little to the history and clinical examination.(137) There is little, if any, value in typing for forensic purposes.

Molecular diagnosis relies on the detection of HPV DNA (see Molecular (DNA) Diagnosis of Anogenital HPV Infections). The use of PCR is highly sensitive, but there is always a risk of contamination. Many HPV types have been described, but no specific type is invariably associated with a particular clinical appearance.(138) Infection with multiple types is common (139) and it is technically impossible to be sure that all types from a given patient have been isolated. HPV DNA can be found in apparently normal tissue surrounding clinical lesions (134) and in vaginal washings from patients with no detectable lesions.(140,141) In adolescents and adults, types 1–4 and 7 are found almost exclusively in skin warts.(138) In children, however, there is a significant prevalence of types 1–3 in anogenital warts.(142,143) Laryngeal papillomas are usually, but not always, associated with HPV types 6 or 11.(91,144)

Neoplasia

Malignancy has been reported in children with laryngeal papillomatosis.(145) The risk of late malignancy in children with anogenital infection is not known. There are case reports of vulval dysplasia and carcinoma in young adolescents who had vulval warts from infancy (146,147) and of Bowenoid papulosis (intraepithelial neoplasia) in childhood.(148,149) There is no data that early screening in this group improves outcome. Cervical screening in girls who have had a history of sexual contact/abuse or exposure to HPV in childhood should commence at the age recommended by the National Cervical Screening Programme (i.e. not earlier).

Methods of transmission in childhood

In adults, anogenital HPV is a sexually transmitted infection. Sexual transmission clearly occurs in children, but other forms of transmission also occur.

Sexual transmission: It was not recognised until 1971 that anogenital warts in children might be sexually transmitted. From 1971 to 1993, 300 cases were published, of which 29% were sexually transmitted. The percentage of sexual abuse in various studies varied from 0–100%, which may have reflected differences either in the populations studied or in the methodology.(131) A recent multi-centre study found a prevalence of HPV of 13.7% in children referred for possible sexual abuse, compared with 1.3% in a control group.(150)

Sexual abuse has been documented in infants whose warts presented as early as the first year of life,(151) and suggested in some cases of oral or laryngeal papilloma. However, accumulating evidence suggests that (in young children at least) the presence of warts in the anogenital region or oropharynx and/or the detection of HPV DNA in the anogenital region is not, in isolation, a reliable indicator of childhood sexual abuse.(94,152-159) The American Academy of Pediatrics (AAP) guidelines conclude that “genital warts (human papillomavirus) can be sexually transmitted in children, but these infections are not diagnostic of abuse by themselves”.(160)

Vertical transmission: HPV can be transferred from mothers to their offspring, probably from an infected birth canal.(96) It is difficult to quantify the risk to these babies, but it appears low.(97,161) There is no correlation between the presence of HPV DNA in the baby and the presence or absence of known clinical or virologic infection in the mother. The duration of viral shedding and/or persistence of HPV DNA on the skin of infected babies remains unclear. Some authors have reported persistence of HPV DNA to 2 years of age,(129,162) but other longitudinal studies have found almost no evidence of persistent perinatally acquired infection.(161,163)

Vertical transmission may also cause juvenile onset respiratory papillomatosis (laryngeal papillomas) that may present as hoarseness, or rarely as recurrent pneumonia or breathing difficulties due to lower respiratory tract involvement.(91,164) The upper limits of the incubation period from birth to clinical infection have not been established, but in laryngeal disease may be as long as 5 years.(157,165)

Given that symptom-free infection is common in pregnancy (see above), one cannot completely exclude the possibility of vertical transmission in any child. However, one should remember that maternal infection does not prove vertical transmission. Several cases have been described in which the mother’s sexual partner was abusing the child.(165,166) On the basis of the evidence to date, it is reasonable to conclude that most vertical transmission will manifest itself in young children and that child sexual abuse is not the most likely cause of HPV in the majority of cases involving children under the age of 4 years.(148,157,167)

Other means of transmission: Dermatological literature suggests that children may acquire anogenital warts by infection from cutaneous warts on their own hands (auto-inoculation), or on the hands of adults (hetero-inoculation). Arguments for this hypothesis are the prevalence of HPV 2 in anogenital warts in childhood, and a number of suggestive case reports and case series.(39,127,142) A Spanish longitudinal study of women enrolled during pregnancy found that the mother’s HPV status at the 6 week post-partum visit was a stronger determinant of HPV infection in the child than maternal HPV status in pregnancy, and suggested that horizontal mother-to-child transmission during the first few months of life might be more important than vertical transmission.(163) Similarly, other authors have also raised the possibility of fomite transmission.(156)

In conclusion, it must be recognised that methods of transmission other than sexual transmission do occur in children, particularly in those under the age of 4 years. However, sexual contact must always be considered in the differential diagnosis, and even in young children a comprehensive multi-disciplinary assessment may be required if there are any other factors which cause concern.

Assessment

Establish the age at which the lesions first appeared, and what symptoms they cause. Consider all means of transmission: vertical (maternal infection including cervical smears; symptoms of respiratory infection); innocent inoculation (other warts in the child or young person; warts in other relatives or caregivers); sexual transmission (adolescent sexual activity; disclosure of sexual abuse; behaviour changes; risk factors for sexual abuse, such as contact with a known sexual offender or a family history of sexual abuse).

Do not forget to examine the whole body (including the conjunctivae, mouth and throat) for warts. Examine the genitalia and anus with a light source and some kind of magnification, such as an auroscope. In females, part the labia and inspect the vulva carefully. In males, do not forget to examine the corona and frenum of the penis (if the foreskin is readily retractile). Not everything that presents as a wart is HPV. The most common alternative diagnosis is molluscum contagiosum, but condyloma lata (syphilis) has been mistaken for genital warts in a child,(168) and almost any kind of papular rash may present in the anogenital region. The diagnosis can usually be made clinically if the child is seen by an experienced clinician, and biopsy is seldom indicated.

If a child under 4 years old presents with anogenital warts, further assessment for sexual abuse is probably not indicated in most cases, unless there are factors in addition to the warts themselves which raise concern. In older children, or if there are other factors which cause concern, consider referral for a multidisciplinary assessment for possible sexual abuse. If in doubt, consult with a paediatrician with expertise in this area. If you do refer, leave other investigations for sexual abuse to the doctor to whom you are referring. A full assessment for possible sexual abuse will include an examination by a doctor trained in the medical assessment of sexual abuse, screening for other STI, and consideration of referral to the statutory authorities for further investigation. Even then, the result may be inconclusive.(169)

More extensive medical investigations (such as laryngoscopy, proctoscopy, cystoscopy or vaginoscopy) might rarely be indicated if there were oral lesions or respiratory symptoms in a young child, or if lesions appeared to extend into the anus, urethra or vagina.

Treatment

Anogenital warts will usually regress spontaneously. Infection may be multi-focal, and HPV DNA is almost certainly present in adjacent ‘normal’ tissue. At present, there is no evidence that treatment in childhood will reduce the (unproven) risk of later neoplasia. Treatment ”can be difficult, prolonged and only marginally efficacious”(123) and recurrence is common. For all these reasons, active treatment is not usually recommended. Treatment should be reserved for those with significant symptoms. There are many forms of treatment,(156,170,171) but in young children with extensive lesions, laser or diathermy under general anaesthetic is probably the best option. Several case reports attest to the safety and efficacy of Podofilox gel (podophyllotoxin) or imiquimod cream in children.(172) However, there are no randomised controlled trials of therapy in childhood. The most common therapy for juvenile onset respiratory papillomatosis is laryngoscopy and surgical debulking with laser, sometimes in conjunction with adjuvant antiviral agents.(173)

Follow-up

Follow the patient to ensure that the lesions regress, and see them again after 3–6 months to ensure that they have not recurred. In the case of vertical transmission, it is important to ensure that the mother receives appropriate follow-up of her own infection. If the patient is a sexually active adolescent, you should screen for other STIs and provide sexual health advice. In the case of sexual abuse, the patient should be followed to ensure that appropriate steps have been taken to ensure his or her ongoing safety and to provide support and counselling.

There is no evidence available to guide recommendations for long-term follow-up. It is reasonable to be concerned that children and adolescents with anogenital HPV infection may be at increased long-term risk of malignancy. Therefore, it would be reasonable to recommend early consultation by patients of either sex for anogenital or urethral symptoms. Routine cervical screening should follow the National Cervical Screening Guidelines.