title: Human papillomavirus 16-specific cell-mediated immunity in children born to mothers with incident cervical intraepithelial neoplasia (CIN) and to those constantly HPV negative.
abstract: OBJECTIVE
  HPV 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.
  
  
  METHODS
  Peripheral 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.
  
  
  RESULTS
  All 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).
  
  
  CONCLUSIONS
  HPV16-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.
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Faculty of Medicine, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20540, Turku, Finland. hakosk@utu.fi.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Koskimaa
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Faculty of Medicine, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20540, Turku, Finland. aepaas@utu.fi.
authors.forename: Anna
authors.initials: A
authors.lastname: Paaso
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. M.J.P.Schoenmaekers-Welters@lumc.nl.
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland. Seija.Grenman@tyks.fi.
authors.forename: Seija
authors.initials: S
authors.lastname: Grénman
authors.affiliation: Department of Clinical Research, Biohit Oyj, Helsinki, Finland. kari.syrjanen@biohit.fi.
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. S.H.van_der_Burg@lumc.nl.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.affiliation: Medicity Research Laboratory and Department of Oral Pathology, Faculty of Medicine, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20540, Turku, Finland. stina.syrjanen@utu.fi.
authors.forename: Stina
authors.initials: S
authors.lastname: Syrjänen
mesh_terms: D002648:Child; D016207:Cytokines / Q000378:metabolism; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007111:Immunity, Cellular; D008137:Longitudinal Studies; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D016207:Cytokines