Rinne Sanni, Michels Birgitta, Butt Julia, Syrjänen Kari, Grenman Seija, Waterboer Tim, Syrjänen Stina, Louvanto Karolina
Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Microbiol Spectr. 2025 Sep 2;13(9):e0007125. doi: 10.1128/spectrum.00071-25. Epub 2025 Aug 1.
Epstein-Barr virus (EBV) and various human papillomaviruses (HPVs) commonly infect the oral mucosa, yet the longitudinal effects of these infections and their potential coinfections remain poorly understood. This study investigated whether early EBV infection and antibody responses influence oral HPV infections in young children. We included 283 children from the Finnish Family HPV cohort study, who were followed for 3 years post-birth. Oral and blood samples were collected at six time points (1, 2, 6, 12, 24, and 36 months). HPV genotyping was performed with Luminex and EBV-IgG antibodies to Zebra, early antigen-diffuse (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 with fluorescent bead-based multiplex serology. We noticed that most children (91.4%; = 254) experienced the vanishing of maternal EBV-IgG antibodies within 11.3 months, and by 36 months, 17% (41/238) of the children had developed their own EBV antibodies. Intriguingly, higher paternal education levels were strongly associated with lower EBV seropositivity in children at ages 2 and 3, with an odds ratio(OR) range of 0.06 to 0.16 (95% confidence interval range 0.005-0.91). Additionally, children with the highest baseline titers of EA-D antibodies had 2.5- and threefold risk for incident oral HPV infection and its clearance, respectively. Our findings suggest that EBV seropositivity at 3 years of age is relatively low in our Finnish data, and the level of paternal education was a significant protective factor against early EBV seropositivity. Moreover, the observed association between high EA-D antibody titers and oral HPV infection underscores the need for further research into the complex interactions between EBV and HPV.IMPORTANCEEpstein-Barr virus (EBV) and human papillomaviruses (HPVs) are known to cause cancers in the head and neck region, yet their interactions in young children remain largely unexplored. EBV, associated with infectious mononucleosis, and oral HPV, often asymptomatic in early childhood, target similar anatomical regions but are poorly studied together in this age group. Understanding these interactions is crucial, as the incidence of HPV-related oropharyngeal cancers has been rising over recent decades, making the natural history of oral HPV infections a critical research focus. While our study found no significant link between EBV seropositivity and oral HPV outcomes in children, evidence in adults suggests these viruses may interact in cancer development. Investigating this dynamic in early childhood could provide valuable insights into infection patterns and inform prevention strategies to reduce cancer risks later in life.
爱泼斯坦-巴尔病毒（EBV）和多种人乳头瘤病毒（HPV）通常会感染口腔黏膜，但这些感染及其潜在合并感染的纵向影响仍知之甚少。本研究调查了早期EBV感染和抗体反应是否会影响幼儿的口腔HPV感染。我们纳入了芬兰家庭HPV队列研究中的283名儿童，对他们出生后3年进行随访。在六个时间点（1、2、6、12、24和36个月）采集口腔和血液样本。使用Luminex对HPV进行基因分型，并采用基于荧光微球的多重血清学方法检测针对斑马蛋白、早期抗原弥漫型（EA-D）、EBV核抗原1和病毒衣壳抗原p18的EBV-IgG抗体。我们注意到，大多数儿童（91.4%；n = 254）在11.3个月内母体EBV-IgG抗体消失，到36个月时，17%（41/238）的儿童产生了自身的EBV抗体。有趣的是，父亲受教育程度较高与2岁和3岁儿童较低的EBV血清阳性率密切相关，优势比（OR）范围为0.06至0.16（95%置信区间范围为0.005 - 0.91）。此外，EA-D抗体基线滴度最高的儿童发生口腔HPV感染及其清除的风险分别为2.5倍和3倍。我们的研究结果表明，在我们的芬兰数据中，3岁时EBV血清阳性率相对较低，父亲的教育水平是预防早期EBV血清阳性的重要保护因素。此外，观察到的高EA-D抗体滴度与口腔HPV感染之间的关联强调了进一步研究EBV与HPV之间复杂相互作用的必要性。
重要性
已知爱泼斯坦-巴尔病毒（EBV）和人乳头瘤病毒（HPV）会导致头颈部癌症，但其在幼儿中的相互作用在很大程度上仍未得到探索。与传染性单核细胞增多症相关的EBV和在幼儿期通常无症状的口腔HPV靶向相似的解剖区域，但在这个年龄组中对它们的共同研究很少。了解这些相互作用至关重要，因为近几十年来HPV相关口咽癌的发病率一直在上升，使得口腔HPV感染的自然史成为关键的研究重点。虽然我们的研究未发现儿童EBV血清阳性与口腔HPV结局之间存在显著关联，但成人的证据表明这些病毒可能在癌症发展中相互作用。在幼儿期研究这种动态变化可以为感染模式提供有价值的见解，并为降低生命后期癌症风险的预防策略提供依据。
