TY - JOUR
T1 - Programmed death-1 (PD-1) expression in cervical intraepithelial neoplasia and its relationship with recurrence after conization
AU - Chang, Hyeyoon
AU - Hong, Jin Hwa
AU - Lee, Jae Kwan
AU - Cho, Hyun Woong
AU - Ouh, Yung Taek
AU - Min, Kyung Jin
AU - So, Kyeong A.
N1 - Publisher Copyright:
© 2018, Korean Society of Gynecologic Oncology and Colposcopy. All rights reserved.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Cervical intraepithelial neoplasia
KW - Papillomaviridae
KW - Programmed cell death-1
UR - http://www.scopus.com/inward/record.url?scp=85047063270&partnerID=8YFLogxK
U2 - 10.3802/jgo.2018.29.e27
DO - 10.3802/jgo.2018.29.e27
M3 - Article
C2 - 29400020
AN - SCOPUS:85047063270
SN - 2005-0380
VL - 29
JO - Journal of Gynecologic Oncology
JF - Journal of Gynecologic Oncology
IS - 3
M1 - e27
ER -