Statin use and clinical outcomes in patients with head and neck cancer: a systematic review and meta-analysis

Statins, widely used for cardiovascular disease prevention, have shown potential antitumor effects through anti-inflammatory, immunomodulatory, and antiproliferative mechanisms. This systematic review and meta-analysis evaluated the association between statin use and clinical outcomes in patients with head and neck cancer (HNC). A comprehensive search of PubMed, EMBASE, CINAHL, Web of Science, and the Cochrane Library was conducted up to February 2025. Clinical trials and observational studies assessing statin use in HNC were included. We meta-analyzed hazard ratios (HRs) for four outcomes—overall survival, cancer-specific survival, recurrence, and stroke incidence—and summarized non-poolable studies qualitatively. Subgroup analyses were stratified by HNC type, risk of bias (adjusted vs. KM-reconstructed HRs), and handling of immortal time bias (ITB). Statin use was significantly associated with reduced cancer-specific mortality ( N = 5 studies; HR, 0.67; 95% CI, 0.54–0.81), and all-cause mortality ( N = 10; HR, 0.76; 95% CI, 0.70–0.82), along with a modest reduction in recurrence ( N = 4; HR, 0.84; 95% CI, 0.73–0.96). These associations remained consistent when the analysis was restricted to low-risk-of-bias studies reporting fully adjusted HRs, and ITB-robust studies consistently yielded numerically lower HR than ITB-present studies for all outcomes. No significant association was found for stroke incidence ( N = 3; HR, 0.76; 95% CI, 0.40–1.45). Mortality evidence came mainly from head and neck squamous cell carcinoma (HNSCC) cohorts; restricting the analysis to these cohorts minimized heterogeneity while preserving the significant inverse association (all-cause HR, 0.76 [95% CI, 0.69–0.83; I 2 , 8.7%]; cancer-specific HR, 0.73 [95% CI, 0.63–0.85; I 2 , 0%]). Given the low certainty of the predominantly observational evidence according to the GRADE framework, more robust causal evidence is needed. Future research should emulate a target trial in large healthcare databases to minimize biases, with pre-specified evaluations of effect modification by clinical and pharmacological factors. Systematic review registration PROSPERO CRD420251008783