PO.PR01.02 · 预防研究
程序性死亡配体1的免疫组化表达与人乳头瘤病毒驱动的高级别宫颈上皮内瘤变的关联
Immunohistochemical expression of programmed death-ligand 1 associated with human papillomavirus-driven high-grade cervical intraepithelial neoplasia
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景
宫颈癌是南非女性中第二常见的恶性肿瘤，高危型人乳头瘤病毒（HPV）感染是其关键危险因素。HPV在宫颈癌变中发挥核心作用，尤其是在高级别鳞状上皮内病变（HSIL）中。已有报道在宫颈癌中存在程序性死亡配体1（PD-L1）表达，且与肿瘤免疫逃逸相关；然而其在浸润前高级别宫颈上皮内瘤变（CIN）中的作用仍不完全清楚。本研究采用免疫组化方法，探讨高危型HPV驱动的高级别CIN与PD-L1表达之间的关系。
方法
我们开展了一项分析性横断面研究，使用来自比勒陀利亚大学解剖病理学系、于2018年至2021年间收集的宫颈组织存档标本。纳入研究的标本包括宫颈环形电切术、锥切活检、钳取活检和息肉切除术的福尔马林固定、石蜡包埋标本。PD-L1表达采用联合阳性评分（CPS）进行评估。三位病理学家独立评估了组织学分级、作为高危型HPV替代指标的p16免疫组化以及PD-L1表达。
结果
共纳入108例患者，平均年龄37.36岁。大多数病变为CIN III（89.8%），CIN II（9.3%）和CIN II-III（0.9%）病变所占比例较小。97.2%的病例p16表达阳性，支持其与高危型HPV的关联。PD-L1表达（定义为CPS≥1）在9.3%的病例中被发现，平均CPS为1.57。PD-L1表达与CIN分级之间（p = 0.6433，Cramer's V = 0.1191）以及PD-L1表达与p16阳性之间（p = 1.000，Cramer's V = 0.05976）均无统计学显著关联。
结论
在这一高危型HPV驱动的高级别CIN队列中，PD-L1表达不常见，且与CIN分级或p16状态无相关性。从表面看，这些发现提示针对PD-L1的免疫检查点抑制在HSIL阶段不太可能发挥主要治疗作用。然而，PD-L1阳性频率相对较低以及横断面设计意味着不能排除细微的预后效应，开展更大规模的基于结局的研究将有助于阐明一小部分高级别CIN是否仍可能从免疫调节方法中获益。
查看英文原文 English abstract
Background
Cervical cancer is the second most common malignancy among South African women, with high-risk human papillomavirus (HPV) infection as a key risk factor. HPV plays a central role in cervical carcinogenesis, particularly in high-grade squamous intraepithelial lesions (HSIL). Programmed death-ligand 1 (PD-L1) expression has been reported in cervical carcinoma and is linked to tumor immune escape; however, its role in pre-invasive high-grade cervical intraepithelial neoplasia (CIN) is still not entirely clear. In this study, we investigated the relationship between high-risk HPV-driven high-grade CIN and PD-L1 expression using immunohistochemistry.
Methods
We conducted an analytical cross-sectional study using archival cervical tissue from the Department of Anatomical Pathology, University of Pretoria, collected between 2018 and 2021. Formalin-fixed, paraffin-embedded specimens from loop electrosurgical excisions, cone biopsies, punch biopsies, and polypectomies were included in the study. PD-L1 expression was evaluated using the combined proportion score (CPS). Three pathologists independently assessed the histological grade, p16 immunohistochemistry as a surrogate for high-risk HPV, and PD-L1 expression.
Results
A total of 108 patients were included, with a mean age of 37.36 years. Most lesions were CIN III (89.8%), with smaller proportions of CIN II (9.3%) and CIN II-III (0.9%) lesions. p16 expression was positive in 97.2% of cases, supporting the association with high-risk HPV. PD-L1 expression, defined as CPS ≥1, was identified in 9.3% of the cases, with a mean CPS of 1.57. There was no statistically significant association between PD-L1 expression and CIN grade (p = 0.6433, Cramer's V = 0.1191) or between PD-L1 expression and p16 positivity (p = 1.000, Cramer's V = 0.05976).
Conclusion
In this cohort of high-risk HPV-driven high-grade CIN, PD-L1 expression was infrequent and did not correlate with CIN grade or p16 status. Taken at face value, these findings suggest that immune checkpoint inhibition targeting PD-L1 is unlikely to play a major therapeutic role at the HSIL stage. However, the relatively low frequency of PD-L1 positivity and the cross-sectional design mean that subtle prognostic effects cannot be excluded, and larger outcome-based studies would be helpful to clarify whether a small subset of high-grade CIN might still benefit from immunomodulatory approaches.
利益披露 Disclosure
J. McIntyre, None..
R. Marima, None..
B. Alabi, None..
T. Marutha, None..
Z. Dlamini, None..
B. Mosoane, None.