Treatment of Pediatric Anogenital Warts in the Era of HPV-Vaccine: A Literature Review

Abstract

Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.

Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts

“…The burden of HPV infections and HPV-related diseases has led to increasing efforts of the scientific community to develop efficacious strategies for infection prevention. Among these, HPV vaccines are being administered worldwide and have already proven effective in reducing HPV infection rates and HPV-related diseases [18,19]. In 2006, the first quadrivalent HPV vaccine (Gardasil ® ), containing protein antigens for HPV types 6, 11, 16, and 18, was commercialized in most industrialized countries.…”

“…The bivalent vaccine (Cervarix ® ), licensed in 2007, targets HPV types 16 and 18. Lastly, the nonavalent HPV vaccine (Gardasil 9), licensed in 2014, targets HPV types 6,11,16,18,31,33,45,52, and 58 [4,19]. These vaccines are composed of recombinant, non-infectious virus-like particles (VLP), antigenically identical to infection-causing HPV virions, and induce a humoral neutralizing immune response in the host that efficiently halts the viral uptake into basal epithelial cells [4].…”

“…To date, knowledge of the possible therapeutic effect of the HPV vaccine on alreadyestablished HPV infections and HPV-related disease is limited [4,18]. Considering the significant psychological and social distress that these lesions often cause to patients [17] and their frequent recurrence after conventional therapies [19], a possible combined effect, both therapeutic and preventive, of an HPV vaccination, would have revolutionary potential.…”

Clinical features of atopic dermatitis in pediatric patients with skin of color and comparison with different phototypes

“…1,2 Moreover, the weak skin barrier in AD facilitates the acquisition of infections, such as cutaneous and mucosal warts, and viral persistence, in addition to hindering therapeutic methods. 3 Precocious recognition of AD is of utmost importance to avoid unnecessary medical procedures and to establish a successful treatment together with effective educational programs for pediatric patients and their caregivers. However, AD may have very different clinical features, and wide clinical heterogeneity exists across different skin types.…”

“… 1 , 2 Moreover, the weak skin barrier in AD facilitates the acquisition of infections, such as cutaneous and mucosal warts, and viral persistence, in addition to hindering therapeutic methods. 3 …”