Backround HPV causes specific cell-mediated immunity in the cervix. Mononuclear cells such as helper T cells (CD4+), cytotoxic T cells (CD8+), and dendritic cells play a critical role in the initiation of the HPV-specific immune response and destruction of virus-infected cervical epithelial cells. The programmed cell death ligand 1 (PD-L1) gene encodes an immune inhibitory receptor ligand and overexpression of PD-L1 inhibits T-cell activation and cytokine production. The aim of this study was to investigate the expression of PD-L1 in cervical tissue and its correlation with clinicopathological findings. Methods In this cross-sectional study, a total of 94 women who were referred for colposcopy due to abnormal Papanicolaou (PAP) test results and/or HPV positivity were evaluated. The presence of HR-HPV–DNA was analyzed using type- and gene-specific primers along with commercial real-time polymerase chain reaction. The cervical examination was done with a colposcope. Cervical biopsies were obtained from the areas that were evaluated as abnormal during the colposcopy. Histopathological result of cervical biopsies were defined as no intraepithelial neoplasia (CIN 0), mild CIN (CIN I), and moderate-to-high CIN (CIN II-III). All women were classified into four groups based on their HR-HPV positivity and cervical biopsy results: Group I (controls; n = 29), HR-HPV (−) CIN 0; Group II ( n = 21), HR-HPV (+) CIN 0; Group III ( n = 20), HR-HPV (+) CIN I; and Group IV ( n = 24), HR-HPV (+) CIN II-III. A semi-quantitative scoring system was used to evaluate the degree of Ki-67, p16, and PD-L1 immunoreactivity in the cervical tissue samples. Results We found that PD-L1 expression in both mononuclear cells and in cervical epithelial cells gradually increases from the HR-HPV (−), CIN 0 group to the HR-HPV (+), CIN II-III group ( p = 0.0003 and p = 0.0394, respectively) and mononuclear PD-L1 expression was correlated with HPV type, initial Pap test results, HPV persistence, and CIN persistence or recurrence ( p = 0.0180, p = 0.0109, p = 0.0042, and p = 0.0189, respectively). Moreover, mononuclear PD-L1 expression was also correlated with Ki-67 and p16 immunoreactivity ( p = 0.0432 and p = 0.0166, respectively). Epithelial PD-L1 expression was only correlated with HPV type and the presence of HPV persistence ( p = 0.0122 and p = 0.0292, respectively). Conclusion During the initial evaluation of the cervical histology results, the assessment of PD-L1 expression—especially in mononuclear cells in cervical tissue samples—may provide more information on the progression of HR-HPV infection and its persistence.

中文翻译：

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CIN患者程序性细胞死亡配体1的过表达及其与人乳头瘤病毒感染和CIN持续存在的相关性

背景 HPV 在子宫颈中引起特异性细胞介导的免疫。单核细胞如辅助 T 细胞 (CD4+)、细胞毒性 T 细胞 (CD8+) 和树突状细胞在启动 HPV 特异性免疫反应和破坏病毒感染的宫颈上皮细胞中起关键作用。程序性细胞死亡配体 1 (PD-L1) 基因编码免疫抑制受体配体，PD-L1 的过表达抑制 T 细胞活化和细胞因子产生。本研究旨在探讨 PD-L1 在宫颈组织中的表达及其与临床病理结果的相关性。方法 在这项横断面研究中，共有 94 名因巴氏试验 (PAP) 检测结果异常和/或 HPV 阳性而被转诊进行阴道镜检查的女性进行了评估。使用类型和基因特异性引物以及商业实时聚合酶链反应分析 HR-HPV-DNA 的存在。宫颈检查是用阴道镜完成的。宫颈活检取自在阴道镜检查期间被评估为异常的区域。宫颈活检组织病理学结果定义为无上皮内瘤变（CIN 0）、轻度CIN（CIN I）和中度至高度CIN（CIN II-III）。根据 HR-HPV 阳性和宫颈活检结果将所有女性分为四组：I 组（对照组；n = 29），HR-HPV（-）CIN 0；第二组（n = 21），HR-HPV（+）CIN 0；III 组 (n = 20)，HR-HPV (+) CIN I；和第四组（n = 24），HR-HPV（+）CIN II-III。采用半定量评分系统评估 Ki-67、p16、和宫颈组织样本中的 PD-L1 免疫反应性。结果我们发现PD-L1在单核细胞和宫颈上皮细胞中的表达从HR-HPV（-）、CIN 0组逐渐升高到HR-HPV（+）、CIN II-III组（p = 0.0003和p = 0.0394）和单核 PD-L1 表达与 HPV 类型、初始巴氏试验结果、HPV 持续性和 CIN 持续性或复发相关（分别为 p = 0.0180、p = 0.0109、p = 0.0042 和 p = 0.0189 ）。此外，单核 PD-L1 表达也与 Ki-67 和 p16 免疫反应性相关（分别为 p = 0.0432 和 p = 0.0166）。上皮 PD-L1 表达仅与 HPV 类型和 HPV 持续存在相关（分别为 p = 0.0122 和 p = 0.0292）。结论 在对宫颈组织学结果进行初步评估时，