High-density lipoprotein-related inflammatory indices and gynaecological cancer history: a cross-sectional analysis of NHANES

Background Cross-sectional associations of high-density lipoprotein-related inflammatory indices (HIRIs) – white-blood-cell-, lymphocyte-, monocyte-, neutrophil-, and platelet-to-high-density lipoprotein cholesterol (HDL-C) ratios (WHR, LHR, MHR, NHR, and PHR) – with self-reported gynaecological cancer (GC) history are unclear.Methods We analysed 12,955 women from six National Health and Nutrition Examination Survey cycles (2007–2008 to 2017–March 2020 pre-pandemic), including 369 with GC history; cervical cancer (CC), 184; uterine cancer (UC), 127; and ovarian cancer (OC), 70. Primary analyses used survey-weighted logistic regression and restricted cubic spline (RCS) models with Benjamini–Hochberg false discovery rate (BH-FDR) correction; component-resolved and sensitivity analyses were supportive, and other secondary analyses were exploratory.Results In fully adjusted models, overall GC history was nominally associated with PHR (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.01–1.59; p = 0.045), the highest NHR tertile (OR 1.67, 95% CI 1.12–2.50; p = 0.013), and the highest WHR tertile (OR 1.56, 95% CI 1.04–2.34; p = 0.032). Subtype analyses showed selected nominal patterns, including an NHR tertile gradient for CC and WHR/LHR/PHR associations for UC; OC estimates were less stable. No primary logistic or RCS result survived BH-FDR correction. In supportive component-resolved analyses, the OC WHR white-blood-cell component met the BH-FDR threshold within the prespecified WHR-specific eight-test family (OR 2.40, 95% CI 1.35–4.25; p = 0.003; q = 0.025).Conclusions HIRIs showed modest, heterogeneous cross-sectional associations with self-reported GC history, but the primary findings were not retained after multiplicity correction. These ratios appear to reflect both shared HDL-C and numerator-cell information and should be interpreted as descriptive, hypothesis-generating phenotypes rather than diagnostic, prognostic, or causal markers.