SynthesisFrontiers in oncology2026
Clinicopathological features and survival outcomes of HPV-independent versus HPV-associated cervical adenocarcinoma: a Systematic Review and meta-analysis.
Synthesis in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
Background: Human papillomavirus (HPV)-independent cervical adenocarcinoma is increasingly recognized as a biologically and clinically distinct entity from HPV-associated adenocarcinoma. We aimed to compare the clinicopathological features and survival outcomes of HPV-independent versus HPV-associated cervical adenocarcinoma. Methods: We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase, and the Cochrane Library were searched from inception to 01 March 2026. Comparative studies evaluating HPV-independent/non-HPV-associated and HPV-associated cervical adenocarcinoma were included. Primary outcomes were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Secondary outcomes included distant metastasis/distant recurrence, local recurrence, and lymphovascular space invasion/lymphovascular invasion (LVSI/LVI) positivity. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models according to heterogeneity. Results: HPV-independent/non-HPV-associated adenocarcinoma was associated with poorer OS (pooled HR 3.37, 95% CI 2.12-5.36) and PFS (pooled HR 2.94, 95% CI 2.01-4.31) than HPV-associated adenocarcinoma. DFS was worse in the primary analysis (pooled HR 2.56, 95% CI 1.15-5.72), but became non-significant in sensitivity analysis after exclusion of one study requiring reciprocal transformation (HR 2.02, 95% CI 0.87-4.66). HPV-independent/non-HPV-associated adenocarcinoma also showed higher risks of distant metastasis/distant recurrence (pooled OR 2.76, 95% CI 1.88-4.05), local recurrence (pooled OR 2.76, 95% CI 1.82-4.19), and LVSI/LVI positivity (pooled OR 3.00, 95% CI 2.07-4.35). Conclusions: HPV-independent/non-HPV-associated cervical adenocarcinoma is associated with more aggressive clinicopathological features and worse survival outcomes than HPV-associated adenocarcinoma. These findings support the distinct clinical behavior of HPV-independent disease and may inform risk stratification and management. Systematic Review Registration: PROSPERO, identifier CRD420261348146.
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