Christos V. Chalitsios

Positivity Rate of PD-L1 Expression and Its Clinical Significance in Vulvar Cancer: A Systematic Review and Meta-Analysis

The prevalence and prognostic value of programmed death ligand 1 (PD-L1) expression, as a potential biomarker in vulvar squamous cell carcinomas (VSCCs), remain underexplored. We searched the PubMed, Scopus, Embase, and Cochrane Library databases until July 2024 for articles examining PD-L1 expression in VSCCs. Random-effects meta-analyses summarized PD-L1 expression overall and in subgroups by immunohistochemistry antibody type, positivity cutoff, tumor stage, and HPV positivity. Additionally, random-effects meta-analyses summarized the association between PD-L1 positivity and cancer prognosis. We included 26 studies comprising 1912 VSCC cases. The summary PD-L1 positivity rate in tumor cells was 59.9% (95% confidence interval [CI]: 47.7–71.4%; I2 = 96%, n = 26), influenced by the different cutoff thresholds utilized to define PD-L1 positivity. Compared to tumor cells, positivity rates were higher in intratumoral immune cells (75.6%; 95%CI: 52.9–92.5; I2 = 95.4%, n = 6) and peritumoral cells (78.9%; 95%CI: 54.4–95.5%; I2 = 91%, n = 3) but with overlapping 95%CIs. No heterogeneity was observed in the rates by tumor stage or HPV status. Positive PD-L1 expression was associated with worse overall (hazard ratio [HR] = 1.43; 95%CI: 1.06–1.93; I2 = 28.9%, n = 7) and progression-free survival (HR = 1.57; 95%CI: 1.07–2.3; I2 = 38.3%, n = 5). The PD-L1 expression rate in VSCC tumor cells varied across studies, was influenced by differences in immunohistochemical evaluation, and was identified as an unfavorable prognostic factor. Large, prospective, multicenter studies with standardized protocols are crucial to further elucidate the clinical significance of PD-L1 expression in VSCCs.

Unravelling the association between sleep traits and reproductive cancers: A systematic review and meta-analysis

Sleep traits (duration, insomnia, chronotype, snoring) are modifiable lifestyle factors that may influence cancer risk, but their association with reproductive cancers remains unclear. We systematically searched PubMed, Scopus, and Web of Science (until 09/2024) for observational studies investigating associations between sleep traits and reproductive cancers (including breast, prostate, endometrial, epithelial ovarian). We extracted estimates from maximally adjusted models and performed random-effects and dose-response meta-analyses. This study included 62 observational studies (45 cohort, 17 case-control) from 55 publications, but cohorts were primarily considered in interpretation. Compared to a morning chronotype, evening chronotype was associated with higher risk of breast cancer (HR = 1.12; 95 %CI: 1.07-1.17; I

The role of sleep traits in prostate, endometrial, and epithelial ovarian cancers: An observational and Mendelian randomisation study

Sleep traits may influence cancer risk; however, their associations with prostate (PCa), endometrial (ECa), and epithelial ovarian (EOCa) cancer remain unclear. We conducted an observational analysis using the UK Biobank cohort and a two-sample Mendelian randomisation (MR) analysis to investigate the association between six sleep traits-duration, chronotype, insomnia, daytime napping, daytime sleepiness, and snoring-with PCa, ECa, and EOCa risk. Cox proportional hazards models were used for the observational analysis, while the inverse variance-weighted (IVW) method was applied in MR, with multiple sensitivity analyses. A Bonferroni correction was applied to account for multiple testing. Among 8608 PCa, 1079 ECa, and 680 EOCa incident diagnoses (median follow-up: 6.9 years), snoring was associated with reduced EOCa risk (HR=0.78, 95 %CI: 0.62-0.98), while daytime sleepiness was associated with increased EOCa risk (HR=1.23, 95 %CI: 1.03-1.47). However, these associations were not confirmed in MR. MR suggested higher odds of PCa (OR Sleep traits were not associated with PCa, ECa, or EOCa risk; however, an evening chronotype may increase PCa risk. Further research is needed to verify this association and investigate potential underlying mechanisms.