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KMID : 1137020180290030027
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Journal of Gynecologic Oncology
2018 Volume.29 No. 3 p.27 ~ p.27
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Programmed death-1 (PD-1) expression in cervical intraepithelial neoplasia and its relationship with recurrence after conization
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Chang Hye-Yoon
Hong Jin-Hwa
Lee Jae-Kwan
Cho Hyun-Woong
Ouh Yung-Taek
Min Kyung-Jin
So Kyeong-A
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Abstract
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Objective: Impaired local cellular immunity contributes to persistent human papillomavirus (HPV) infection and development of cervical intraepithelial neoplasia (CIN). Programmed death-1 (PD-1) and its ligands PD-ligand-1 (L1) and PD-L2 are negative regulators of T cell activity in various cancers, but few studies exist. The aim of this study was to determine the clinicopathologic and immunologic parameters (PD-1, PD-L1, and PD-L2) related to the persistence/recurrence of CIN after conization.
Methods: Medical records of 652 patients diagnosed with CIN and underwent conization were reviewed. The associations between clinicopathologic parameters (e.g., age, parity, initial HPV load, etc.) and persistence/recurrence of CIN were analyzed. Expression of PD-1, PD-L1, and PD-L2 was assessed on 100 conization specimens by immunohistochemistry (IHC) in women matched for propensity-score (50 with persistence/recurrence and 50 without).
Results: Initial HPV load (>1,000 relative light unit) and positive margin were shown to be significantly associated with CIN persistence/recurrence (p=0.012 and p<0.001, respectively). Multivariate analysis showed that margin status was an independent predictor of persistence/recurrence (hazard ratio=8.86; 95% confidence interval=1.67?16.81; p<0.001). On IHC analysis, none of the patients expressed PD-L1. PD-1+ T cells were observed in 25 of 100 patients. Also, PD-1+ T cells were significantly correlated with increasing grade of CIN (p=0.031). In addition, patients with persistence/recurrence had increased expression of PD-1 compared with those without (36% vs. 14%, respectively; p=0.020). Although PD-L2 expression did not differ between 2 groups, it was significantly higher in patients with high-grade CIN compared to low-grade (34.7% vs. 12%, respectively; p=0.041).
Conclusion: Positive surgical margin and expression of PD-1+ T cells were associated with CIN persistence/recurrence after conization.
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KEYWORD
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Cervical Intraepithelial Neoplasia, Programmed Cell Death-1, Papillomaviridae
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