Koskimaa Hanna-Mari, Paaso Anna, Welters Marij J P, Grénman Seija, Syrjänen Kari, van der Burg Sjoerd H, Syrjänen Stina
Medicity Research Laboratory and Department of Oral Pathology, Faculty of Medicine, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20540, Turku, Finland.
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
J Transl Med. 2015 Nov 25;13:370. doi: 10.1186/s12967-015-0733-4.
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.
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.
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).
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.
在性幼稚儿童中检测到HPV感染。这引发了关于早期HPV感染在保护或易患进一步HPV感染中所起作用的问题。对10名病例儿童和21名对照儿童的HPV16特异性细胞介导免疫（CMI）进行了研究，病例儿童的母亲在14年随访期间被诊断为偶发性宫颈上皮内瘤变（CIN），对照儿童的母亲始终为HPV阴性。儿童的平均年龄为12.3岁。
从血液中分离外周血单核细胞，并用覆盖HPV16 E2、E6和E7的肽池进行刺激。测定淋巴细胞的增殖、细胞因子的分泌以及调节性T细胞的频率。将结果与HPV状态相关联，并在巢式病例对照研究中进行分析。
除两名对照儿童外，所有儿童均表现出针对HPV16 E2、E6和/或E7肽的CMI，伴有1型和2型细胞因子分泌。在巢式病例对照研究中仅发现两个具有统计学意义的差异；（1）病例儿童对HPV16 E2的TNF-α反应高于对照儿童（p = 0.004），（2）对照儿童对HPV16 E7.2肽池无反应，而10名病例儿童中有3名有反应（p = 0.013）。在随访的某个时间点，分别有50%和57%的病例儿童和对照儿童口腔样本HPV呈阳性。此外，6个月龄前无任何HPV抗体的儿童在暴露于HPV16后，外周血单核细胞的增殖反应比其他儿童更频繁（p = 0.045）。
HPV16特异性CMI在年轻、无性经验的儿童中很常见。这表明儿童口腔HPV感染很常见。我们的结果也可能解释了先前的发现，即一半的健康成年人无论其伴侣/性状况如何，都表现出HPV特异性CMI。
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