High-risk mucosal human papillomavirus infections during infancy & childhood

Abstract

Human papillomaviruses (HPVs) are small DNA tumour viruses associated with a variety of proliferative diseases. More than 100 types have been identified and can broadly be grouped into cutaneous and mucosal types according to their site of infection, and can be further subdivided into low-risk (LR) and high-risk (HR) types depending upon their association with malignancy. The main route of transmission of HR mucosal HPVs is through sexual contact, although the acquisition of virus cannot be entirely explained by this mode alone. Evidence also exists for horizontal transmission by other routes and vertical transmission. HR HPVs, particularly HPV-16, have been detected in oral swabs from new-borns, infants and children. Such alternative modes of transmission and acquisition may have an important impact in several areas, including vaccination strategies, epidemiological studies, and the clinical management of children with HPV-associated diseases. This article reviews the literature describing the detection of HPV infections during infancy and childhood and provides evidence for a role of vertical transmission in the spread of HPV infection.

Introduction

Human papillomaviruses (HPVs) are small DNA tumour viruses, which are widespread in humans and can be grouped broadly into cutaneous and mucosal types according to their site of infection (Tjiong et al., 2001), with further subdivision into high-risk (HR) and low-risk (LR) types, depending upon their association with malignancy. It is well established that HR mucosal HPVs are aetiologic in the development of cervical carcinoma (CaCx) and its precursor lesion, cervical intraepithelial neoplasia (CIN). In South London, HR HPV types 16 (HPV-16) and 18 (HPV-18) account for almost 80% of cervical malignancies (Cavuslu et al., 1997).

Transmission of HR HPVs occurs predominantly via sexual contact (Kjaer et al., 2001), with early records suggesting that CaCx was more common in married women than nuns (Rigoni-Stern, 1842). If sexual transmission of HPVs was the sole route of inoculation, use of condoms should prevent such infections. A meta-analysis concluded data in this area were inconsistent, and while use of condoms may protect against anogenital warts (AGW), CIN and CaCx, they do not prevent HPV infection (Manhart and Koutsky, 2002). A recent study of virgins showed that all women but one were HPV DNA negative at enrolment. Only after first coitus did these women become HPV DNA positive (Kjaer et al., 2001). These data support the sexual transmission of HPVs, but the presence of HPV-6 DNA in one virginal woman raises the possibility of alternative routes of viral acquisition. Discrepancies in the HPV type(s) detected in monogamous partners (Ho et al., 1993) and discordance of HPV-16/18 between married couples has also been documented (Monsonego et al., 1993, Hippelainen et al., 1994). However, these findings describe current infection(s) and it is possible they include a dominant HPV type acquired before the present partner. Thus, similar studies conducted in first time partners, would help confirm and clarify these findings.

In addition to the sexual transmission of HR mucosal HPVs, transmission by horizontal and vertical routes has been identified (Mant et al., 2000, Syrjanen, 2003). These alternative modes of transmission have an important impact upon vaccination strategies, epidemiological studies, clinical management and treatment of infected children with HPV-associated diseases.