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PD-L1 expression in vulvar cancer: a systematic review and meta-analysis
Authors:Louise Baandrup  Freja Lærke Sand  Gitte Lerche Aalborg  Trine J Nøttrup  Anne-Marie K Fiehn  Susanne K Kjaer
Institution:1. Unit of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark;2. Statistics and Data Analysis, Danish Cancer Institute, Copenhagen, Denmark;3. Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;4. Department of Pathology, Zealand University Hospital, Roskilde, Denmark

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;5. Unit of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Abstract:Programmed cell death ligand-1 (PD-L1) expression in cancer may predict clinical response to immunotherapeutic treatment with PD-1/PD-L1 inhibitors. Within the vulvar cancer field, PD-L1 expression has only been assessed by a few studies. We conducted a meta-analysis to examine the prevalence of PD-L1 positivity in vulvar cancer. PubMed, Embase, and Cochrane were searched for articles reporting on PD-L1 expression in vulvar cancer. Study selection and data extraction were performed independently by two authors. We extracted data on PD-L1 prevalence in vulvar cancer according to combined positive score (CPS) and tumour proportion score (TPS). Cutoff values for positivity were ≥1 or ≥10 for CPS and ≥1% and ≥5% for TPS. Random-effects models were used to estimate pooled PD-L1 prevalence, with 95% confidence intervals (CIs). Tests of between-study heterogeneity were evaluated by the I2 statistics. Sources of heterogeneity were explored by subgroup analyses and meta-regression. In total, 19 studies were included. Pooled PD-L1 prevalence in vulvar cancer was 83.4% (95% CI: 70.8–91.3; I2 = 80.0) and 53.9% (95% CI: 37.4–69.6; I2 = 93.0) according to CPS and TPS, respectively. Based on TPS, human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (SCC) showed a lower PD-L1 prevalence (39.9%; 95% CI: 13.3–74.2) compared with HPV-independent SCC (62.6%; 95% CI: 33.7–84.6), but meta-regression showed no significant variation in PD-L1 prevalence by HPV status. PD-L1 prevalence was similar in advanced (44.9%; 95% CI: 29.8–61.1) and localized vulvar cancer (56.7%; 95% CI: 18.9–76.7). In conclusion, PD-L1 expression in vulvar cancer is frequent but between-study heterogeneity was high. Based on a subgroup of heterogenous studies, we found no strong variation in PD-L1 prevalence according to HPV status and stage.
Keywords:meta-analysis  PD-L1  vulvar cancer
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