Human papillomavirus 16-specific cell-mediated immunity in children born to mothers with incident cervical intraepithelial neoplasia (CIN) and to those constantly HPV negative.

Hanna-Mari Koskimaa,Kari Syrjänen,Anna Paaso,Marij J P Welters,Seija Grénman,Stina Syrjänen,Sjoerd H Van Der Burg

doi:10.1186/s12967-015-0733-4

Abstract

ObjectivesHPV infections are detected in sexually naive children. This has raised the question about the role of early HPV infections in either protecting or predisposing to further HPV infections. HPV16-specific cell-mediated immunity (CMI) was studied in 10 case-children born to mothers with an incident cervical intraepithelial neoplasia (CIN) diagnosed during their 14-year follow-up (FU), and in 21 children born to mothers, who remained constantly HPV-negative (controls). The mean age of children was 12.3 years.MethodsPeripheral blood mononuclear cells were isolated from blood and stimulated with peptide pools covering HPV16 E2, E6 and E7. Proliferation of lymphocytes, their secretion of cytokines, and the frequency of regulatory T-cells were determined. The results were correlated with the HPV status and analyzed in a nested case–control setting.ResultsAll children, except two controls, displayed CMI against HPV16 E2, E6 and/or E7 peptides associated with type 1 and 2 cytokine secretion. Only two statistically significant differences were found in the nested case–control setting; (1) case-children had a higher TNF-α response to HPV16 E2 (p = 0.004) than controls and (2) controls had no response to HPV16 E7.2 peptide pool while 3/10 case-children had (p = 0.013). Totally, 50 and 57 % of the cases and controls, respectively, had HPV positive oral samples at some FU-visit. In addition, the children without any HPV antibodies before the age of 6 months showed proliferative responses of PBMC after HPV16 exposure more frequently than other children (p = 0.045).ConclusionsHPV16-specific CMI is common in young, sexually inexperienced children. This suggests that oral HPV infections occur frequently in children. Our results might also explain the previous findings that half of healthy adults demonstrate HPV-specific CMI irrespective of their partner/sexual status.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0733-4) contains supplementary material, which is available to authorized users.

Highlights

Human papillomavirus (HPV) is the main cause of cervical cancer (CC) and important in the etiology of other cancers, such as anal and head and neck cancers
Two statistically significant differences were found in the nested case–control setting; (1) case-children had a higher TNF-α response to HPV16 E2 (p = 0.004) than controls and (2) controls had no response to HPV16 E7.2 peptide pool while 3/10 case-children had (p = 0.013)
HPV16-specific cell-mediated immu‐ nity (CMI) is common in young, sexually inexperienced children. This suggests that oral HPV infections occur frequently in children

Summary

Introduction

Human papillomavirus (HPV) is the main cause of cervical cancer (CC) and important in the etiology of other cancers, such as anal and head and neck cancers. The presence of HPV DNA in the placenta or in the umbilical cord blood increased the risk of oral HPV carriage of the newborn at delivery, and this association between placental HPV and oral HPV remained significant at least for the following 2 months [2]. These observations support the possibility of alternative routes of infection such as vertical transmission via infected placenta, cord blood, ascending cervical infection or infected birth canal, or horizontal transmission e.g. via breast-feeding, digital or oral to oral contacts [3,4,5]

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