Table_1_Interactions between vaginal local cytokine IL-2 and high-risk human papillomavirus infection with cervical intraepithelial neoplasia in a Chinese population-based study.docx

BackgroundAlthough interleukin-2 (IL-2) has long been associated with cancer development, its roles in the development of cervical cancer remains unclear. Few studies examined the associations between IL-2 and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN).
ObjectiveWe aimed to assess the association of IL-2 and high-risk HPV infection with risk of CIN as well as their interactions on the risk of CIN.
DesignWe performed a cross-sectional analysis of screening data in 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China in 2014-2015. Both categorical and spline analyses were used to evaluation the association between IL-2 in the local vaginal fluids and prevalence of CIN. In addition, 1503 controls were followed up until January 31, 2019), the nested case-control study design was adopted to evaluate the association of vaginal lavage IL-2 levels and the risk of CIN progression.
ResultsAfter adjusting for potential confounders, IL-2 levels were statistically inversely associated with prevalence of CIN (the 1st versus 4th quartile IL-2 levels: the respective odds ratio [OR] and 95% confidence intervals [CI] was: = 1.75 [1.37, 2.23] for CIN, 1.32 [1.01, 1.73] for CIN I, and 3.53 [2.26, 5.52] for CIN II/III). Increased IL-2 levels were inversely associated with prevalence of CIN (P-overall<0.01, P-nonlinearity<0.01 for CIN; P-overall<0.01, P-nonlinearity = 0.01 for CIN I; P-overall <0.01, P-nonlinearity = 0.62 for CIN II/III). The highest prevalence of CIN was observed in women with high-risk HPV, who also had the lowest IL-2 levels (P-interaction < 0.01). Nested case-control study observed an inverse association between IL-2 levels and risk of CIN progression (OR=3.43, [1.17, 10.03]).
ConclusionsIL-2 levels in the local vaginal fluids were inversely associated with the risk of CIN in Chinese women either with or without high-risk HPV infection.

背景：尽管白细胞介素-2（interleukin-2, IL-2）长期以来被认为与癌症发生密切相关，但其在宫颈癌发生发展中的具体作用仍未明确。目前鲜有研究探讨IL-2与高危型人乳头瘤病毒（high-risk human papillomavirus, HPV）感染和宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）发病风险之间的关联。
目的：本研究旨在评估IL-2与高危型HPV感染对CIN发病风险的关联，以及二者在CIN发病风险中的交互作用。
设计：本研究对2014-2015年中国山西省一项纳入40000名女性的正在进行中的社区队列研究的筛查数据开展横断面分析，研究对象为2285名年龄介于19~65岁的女性。研究同时采用分类分析与样条分析，评估局部阴道液中IL-2水平与CIN患病率的关联。此外，本研究纳入1503名对照人群并随访至2019年1月31日，采用嵌套病例对照研究设计，评估阴道灌洗液IL-2水平与CIN进展风险的关联。
结果：在校正潜在混杂因素后，IL-2水平与CIN患病率呈显著负相关：IL-2第1四分位数组对比第4四分位数组，CIN的比值比（odds ratio, OR）及95%置信区间（confidence interval, CI）分别为1.75[1.37, 2.23]，CIN I为1.32[1.01, 1.73]，CIN II/III为3.53[2.26, 5.52]。IL-2水平升高与CIN患病率呈负相关（CIN：P总体<0.01，P非线性<0.01；CIN I：P总体<0.01，P非线性=0.01；CIN II/III：P总体<0.01，P非线性=0.62）。高危型HPV感染女性的CIN患病率最高，同时其IL-2水平最低，二者的交互作用具有统计学意义（P交互<0.01）。嵌套病例对照研究结果显示，IL-2水平与CIN进展风险呈负相关（OR=3.43, [1.17, 10.03]）。
结论：中国女性局部阴道液中的IL-2水平与CIN发病风险呈负相关，无论是否合并高危型HPV感染。