HPV Infection in Children and Adolescents-A Comprehensive Review

Abstract

Background: Human Papillomavirus (HPV) is a predominant and clinically significant virus affecting individuals of all ages, including children and adolescents. Despite its well-documented role in adult health, particularly in cervical cancer, HPV's impact on younger populations still remains underexplored. Methods: This review investigates the epidemiology, clinical manifestations, transmission pathways, and historical context of HPV in children and adolescents. Results: The study demonstrates a significant prevalence of HPV DNA within paediatric populations, with diverse clinical manifestations such as verruca vulgaris, anogenital warts, and Juvenile Recurrent Respiratory Papillomatosis, alongside substantiating vertical transmission from mother to infant. We also highlight ground-breaking research milestones, including improvements in genetic studies, the development of HPV vaccines, and ongoing investigations into infection dynamics, and long-term health outcomes. Conclusions: By synthesising existing knowledge, this review aims to enhance clinical decision-making, improve management strategies, and pave the way for future research in HPV-related paediatric diseases.

Keywords: HPV DNA prevalence; HPV-related morbidity; human papillomavirus (HPV); maternal–child transmission; paediatric infections; vertical transmission.

Figure 1

Genomic organisation of HPV 16.

Figure 2

Transmission pathways and clinical outcomes of HPV in neonates and children. HPV is primarily transmitted through sexual contact, but alternative routes of transmission are particularly significant in the paediatric population. These routes are categorised into three main groups: vertical transmission, non-sexual horizontal transmission, and paediatric sexual abuse. This transmission may initially cause a transient HPV infection, which can either resolve spontaneously or progress to a persistent infection. Persistent HPV may either regress on its own or become symptomatic, leading to clinical lesions in various anatomical locations. In neonates and children, HPV often clears naturally.

Figure 3

Manifestations and transmission pathways of HPV during pregnancy. Research into vertical transmission pathways focuses on HPV prevalence during pregnancy. HPV is generally more prevalent in pregnant women due to immune and hormonal changes, which may increase lesion severity. HPV DNA has been detected in samples such as the cervix, serum, urine, placenta, and amniotic fluid, with prevalence varying by sample type. Vertical transmission can occur through three mechanisms: periconceptual (around fertilisation), prenatal (during pregnancy), and perinatal (during or immediately after birth). The virus may be passed from mother to baby through ascending genital tract infections, transplacental transmission, or potentially via the bloodstream. HPV infection has been associated with complications such as preterm birth, membrane rupture, intrauterine growth restriction, low birth weight, and foetal death. This schematic was created using Servier Medical Art templates, which are licensed under CC BY 4.0; https://smart.servier.com (accessed on 20 August 2024).

Figure 4

High-risk Alphapapillomavirus life cycle. (A) HPV infection begins when the virus gains access to the basal layer of epithelial cells through disruptions in the epithelial barrier. The virus’s gene expression is closely tied to the differentiation of epithelial cells. Early in the infection, cells express E6 and E7, which drive the cell cycle and stimulate division. In the middle layers, proteins essential for viral genome amplification are upregulated, facilitating the process. As cells differentiate, HPV enters the productive phase, leading to the expression of late genes, including L1 and L2, culminating in viral assembly and release. (B) However, in HPV-associated neoplasia, late gene expression is delayed, limiting virion production to smaller areas near the epithelial surface. This often results in a non-productive or abortive infection, with deregulated E6/E7 expression facilitating the integration of HPV DNA into the host genome, disrupting normal viral replication and leading to persistent high-level E6/E7 expression, which can contribute to genetic errors in the host.