Serum Interleukin-6 Levels in Endometriosis and Endometriosis-Associated Ovarian Cancer: A Systematic Review and Meta-Analysis Demonstrating a Biological Gradient.

Authors

John J Coté, Remington D Coté, Keara Kennedy, Matthew S Block, Robin Farias-Eisner, Ryan W Walters, Lesley B Conrad

Published in

Journal of minimally invasive gynecology. Jun 21, 2026. Epub Jun 21, 2026.

Abstract

This study quantifies serum/plasma interleukin-6 levels across the healthy-non-endometriosis benign-endometriosis-ovarian cancer spectrum, focusing on pooled geometric means stratified by control type.
PubMed (MEDLINE;1971-present), Scopus (2004-present), CINAHL (1981-present), and Google Scholar were systematically searched from inception to October 31, 2025. Reference lists of included studies and prior meta-analyses were hand-searched.
All articles with quantitative serum/plasma interleukin-6 data in ovarian cancer and/or endometriosis versus at least one control group (healthy, non-endometriosis benign, or endometriosis) were included. Endometriosis was included as a comparator to permit direct evaluation of the biological gradient across the healthy-benign-endometriosis-ovarian cancer spectrum, the primary objective of this study. Exclusions were tissue or peritoneal fluid-only measurements, non-human studies, reviews, editorials, or studies without extractable data. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool, Risk of Bias in Non-randomized Studies of Interventions tool, and the Newcastle-Ottawa Scale. Means and standard deviations were log-transformed; results are presented as geometric means approximating medians. Random-effects meta-analyses and meta-regression were performed for each diagnostic category, with exploratory analyses for endometrioid and clear cell subtypes, endometriosis stage, and ovarian cancer stage. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Of 1,903 records identified, 106 studies (>16,000 participants) were included (63 ovarian cancer [18 with endometriosis], 50 endometriosis-only). Geometric mean interleukin-6 levels increased progressively: healthy controls 5.10 pg/mL (95% CI 3.22-8.1095% PI 0.11-231.45; 42 studies) < non-endometriosis benign 5.89 pg/mL (95% CI 3.24-10.71; 95% PI 0.06-578.65; 28 studies) < endometriosis 10.68 pg/mL (95% CI 6.39-17.84; 95% PI 0.37-312.82; 50 studies) < ovarian cancer 21.67 pg/mL (95% CI 12.27-38.26; 95% PI 0.42-1,124.76; 63 studies). Ovarian cancer versus endometriosis: 2.03-times higher (95% CI 0.95-4.33; p=0.068). Endometrioid: 8.65 pg/mL (5 studies, I²=94%); clear cell: 12.77 pg/mL (4 studies, I²=98%; overlapping CIs).
Interleukin-6 approximately doubles from endometriosis to ovarian cancer overall, supporting inflammation-driven progression. Stratifying endometriosis as a distinct comparator group clarifies the incremental inflammatory burden beyond that seen in other benign conditions and resolves inconsistencies in prior meta-analyses that grouped endometriosis with heterogeneous benign controls. More prospective subtype-specific trials are needed.

PMID:
42323960
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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