International Research Center of Excellence, Abuja, Nigeria.
Department of Biomedical Science, Utrecht University, Utrecht, the Netherlands.
JCO Glob Oncol. 2024 Mar;10:e2300380. doi: 10.1200/GO.23.00380.
Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections.
We used a nonmagnetic bead-based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy.
The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1β, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1β, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections.
Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.
炎症介质是免疫反应的重要调节剂，可调节病毒感染引起的炎症，包括人乳头瘤病毒（HPV）。在这项研究中，我们评估了宫颈免疫介质，包括趋化因子、细胞因子和生长因子与 HPV 感染之间的关系。
我们使用非磁性珠基多重检测法，在一项前瞻性纵向队列设计中，检测了 275 名女性宫颈分泌物中的 27 种免疫介质。所有研究参与者年龄均在 18 岁或以上，有阴道性交史，未怀孕，无宫颈疾病或子宫切除术史。
参与者的平均（±标准偏差）年龄为 41（±8）岁，约一半（51%[141/275]）为 HPV 阳性，其中 7%（10/141）为低危 HPV（lrHPV），61%（86/141）为高危 HPV（hrHPV），32%（45/141）同时感染 lrHPV 和 hrHPV。一些免疫介质的浓度较高与 HPV 感染相关，包括嗜酸性粒细胞趋化因子、干扰素-γ、白细胞介素（IL）-1β、IL-2、IL-4、IL-7、IL-8、IL-9、IL-10、IL-12p70、IL-13、IL-15、巨噬细胞炎症蛋白（MIP）-1α、MIP-1β、激活正常 T 细胞表达和分泌的调节因子（RANTES）和肿瘤坏死因子（TNF）-α以及任何 HPV；IL-2、IL-4、IL-5、IL-7、IL-10、IL-12p70 和 IL-13 以及 lrHPV；以及嗜酸性粒细胞趋化因子、干扰素、IL-1B、IL-4、IL-7、IL-8、IL-9、IL-10、IL-13、IL-15、MIP-1α、MIP-1β、RANTES、TNF-α浓度和 hrHPV 感染。粒细胞巨噬细胞集落刺激因子、白细胞介素-1 受体拮抗剂（IL-1Ra）和单核细胞趋化蛋白-1（MCP-1）浓度较高与 HPV 感染几率降低相关，而 IL-1Ra 和 MCP-1 与 HPV 感染几率降低相关。
在该女性人群中，几种趋化因子、细胞因子和生长因子与 HPV 感染的特定群体有关。这些重要发现有助于了解 HPV 免疫反应、细胞因子谱及其对宫颈发病机制的潜在影响，并为该领域的未来研究提供指导。
