Mei Xionge, Fobian Seth-Frerich, IJff Marloes, Crezee Johannes, van Bochove Gregor G W, van Lonkhuijzen Luc R C W, Mom Constantijne H, van den Broek Colette B M, Koster Jan, de Koning Willem, Stubbs Andrew P, Steenbergen Renske D M, Ten Hagen Timo L M, Vermeulen Louis, Stalpers Lukas J A, Oei Arlene L
Department of Radiation Oncology, Amsterdam UMC, The Netherlands; Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands; Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Department of Radiation Oncology, Amsterdam UMC, The Netherlands; Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands; Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands; Precision Medicine in Oncology (PrMiO), Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Int J Gynecol Cancer. 2025 Jul;35(7):101924. doi: 10.1016/j.ijgc.2025.101924. Epub 2025 May 10.
Human papillomavirus (HPV) infection is the primary cause of cervical cancer. Higher viral load, that is, a greater abundance of HPV DNA in a tumor, has been associated with poorer clinical outcomes, and may play a role in the more accurate prediction of (non-) responders to treatment. In this study, we investigated the correlation between HPV viral load, clinical outcomes, and immune parameters related to HPV infection.
HPV viral load was quantified using quantitative polymerase chain reaction on biopsies from a prospective cohort of women diagnosed with cervical cancer. Patients were categorized into 2 HPV viral load groups based on the optimal fit of a non-linear piecewise regression model. Immunohistochemical staining was used to measure tumor cell characteristics (Ki67, p16, Pan-CK), as well as local tumor immune parameters (CD3, CD4, CD8, FOXP3) and immune checkpoint expression (PD-1, PD-L1). Kaplan-Meier curves were generated to compare recurrence-free and overall survival.
In the 44 women included in our study, high HPV viral load was significantly associated with shorter overall and recurrence-free survival (p = .045 and p = .046, respectively; 2-sided) and positively correlated with an increased risk of lymph node and distant metastasis. In addition, a high HPV viral load was linked to lower percentages of tumor-infiltrating lymphocytes and reduced expression levels of PD-1 and PD-L1.
The viral load of HPV in cervical cancer correlates positively to metastasis and recurrence and negatively to survival rates, potentially because of local immune suppression. These results might indicate a lower response to immune checkpoint inhibition in the high viral load group and that other treatment options should still be explored.
人乳头瘤病毒（HPV）感染是宫颈癌的主要病因。更高的病毒载量，即肿瘤中HPV DNA丰度更高，与较差的临床结局相关，并且可能在更准确预测治疗（无）反应者方面发挥作用。在本研究中，我们调查了HPV病毒载量、临床结局以及与HPV感染相关的免疫参数之间的相关性。
使用定量聚合酶链反应对来自诊断为宫颈癌的前瞻性队列女性的活检组织进行HPV病毒载量定量。根据非线性分段回归模型的最佳拟合将患者分为2个HPV病毒载量组。免疫组织化学染色用于测量肿瘤细胞特征（Ki67、p16、全细胞角蛋白），以及局部肿瘤免疫参数（CD3、CD4、CD8、FOXP3）和免疫检查点表达（PD-1、PD-L1）。生成Kaplan-Meier曲线以比较无复发生存率和总生存率。
在我们研究纳入的44名女性中，高HPV病毒载量与较短的总生存期和无复发生存期显著相关（分别为p = .045和p = .046；双侧），并且与淋巴结转移和远处转移风险增加呈正相关。此外，高HPV病毒载量与肿瘤浸润淋巴细胞百分比降低以及PD-1和PD-L1表达水平降低有关。
宫颈癌中HPV的病毒载量与转移和复发呈正相关，与生存率呈负相关，这可能是由于局部免疫抑制。这些结果可能表明高病毒载量组对免疫检查点抑制的反应较低，并仍应探索其他治疗选择。
