ReviewHigh-risk mucosal human papillomavirus infections during infancy & childhood
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.
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Vertical transmission of mucosal HPVs
Vertical transmission describes the transfer of virus from parent to offspring, and may be acquired from either parent. Via the mother this may occur (i) in utero, across the placenta, (ii) intrapartum, during birth through an infected birth canal, or (iii) postpartum, after delivery by breast-feeding. In the case of HPVs, it is unlikely that virus is transmitted via breast milk, as HPVs do not cause viraemia. However, HPVs have been detected by the polymerase chain reaction (PCR) in amniotic
HR HPV infections in children
Reports of HPV prevalences in cohorts of a similar age to those studied in our laboratory, give conflicting results, but the method used for the detection of HPV affects the rate of positivity (Table 1). The use of PCR demonstrated HPV-16 infections were far more common in asymptomatic women than had previously been reported by other methods (Reed et al., 1993, Zazove et al., 1993), occurring in up to 40% of women (Biswas et al., 1997). Studies where high HPV prevalence rates amongst infant
Summary
In all cases of HPV-associated disease, the rate of viral infection exceeds the rate of associated disease, indicating that host factors contribute to the control and outcome of infection. This has been demonstrated in two ways: (i) low grade CIN lesions often spontaneously regress (Nobbenhuis et al., 2001) and (ii) the prevalence of HPV-associated lesions is greater in immunocompromised populations, such as patients with HIV infection or those receiving iatrogenic immunosuppression (Sun et
Acknowledgements
CM is supported by a grant from The Charitable Foundation of Guy's & St. Thomas’ Hospital, London, UK. The authors would like to thank Dr. J.M. Best for constructive criticism during the preparation of this manuscript.
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