Loharamtaweethong Kongsak, Puripat Napaporn, Praditphol Niphon, Thammasiri Jidapa, Tangitgamol Siriwan
Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok, 10300, Thailand.
Department of Anatomical Pathology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
Ther Adv Med Oncol. 2020 Oct 16;12:1758835920963001. doi: 10.1177/1758835920963001. eCollection 2020.
The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients.
We evaluated HIV-positive ( = 42) and HIV-negative ( = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence hybridization.
Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32-4.36) and HR = 5.33 (1.94-14.61)] and cancer-specific survival [HR = 13.62 (5.1-36.38) and HR = 3.53 (1.43-8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27-8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes.
PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments.
程序性死亡因子1/程序性死亡配体1（PD-1/PD-L1）轴可能是宫颈癌的一个治疗靶点；然而，在人类免疫缺陷病毒（HIV）感染患者中对此了解甚少。
我们评估了42例HIV阳性和110例HIV阴性的局部晚期宫颈癌女性患者的PD-L1表达情况（通过联合阳性评分（CPS）⩾1和肿瘤比例评分（TPS）⩾25%来确定）以及PD-L1拷贝数改变情况（通过荧光原位杂交评估）。
无论HIV感染状态如何，根据CPS⩾1和TPS⩾25%，分别有84.9%和44.8%的病例为PD-L1阳性。按照CPS⩾1标准，HIV阳性和HIV阴性女性的PD-L1阳性率相似，而按照TPS⩾25%标准则存在显著差异。肿瘤大小和宫旁浸润与HIV阴性女性的PD-L1阳性相关，而抗逆转录病毒疗法（ART）与TPS<25%相关。HIV阳性女性中低CD4阳性细胞计数与CPS<1相关。HIV阳性和HIV阴性女性之间在PD-L1拷贝数状态方面未观察到显著差异。PD-L1扩增和多体性与TPS⩾25%独立相关，而宫旁浸润的存在与CPS⩾1独立相关。癌症分期和PD-L1扩增被确定为无复发生存[风险比（HR）=2.40（1.32 - 4.36）和HR = 5.33（1.94 - 14.61）]以及癌症特异性生存[HR = 13.62（5.1 - 36.38）和HR = 3.53（1.43 - 8.69）]的独立预测因素。PD-L1多体性是局部区域无复发生存的独立预测因素[HR = 3.27（1.27 - 8.41）]。HIV感染状态和PD-L1表达（CPS⩾1或TPS⩾25%）与患者不良预后无关。
PD-L1扩增和多体性是宫颈癌中PD-L1表达的最强驱动因素，可能代表抗PD-1/PD-L1治疗的预后生物标志物。宫颈癌生物学特性可能受HIV感染、CD4阳性细胞和HIV治疗的调节。
