Abstract
BACKGROUND: The influence of thyroid dysfunction on the clinical outcomes of head and neck cancer (HNC) patients remains an area of ongoing investigation, with previous studies yielding variable results. Treatments for HNC, particularly radiotherapy, frequently impact thyroid function. This meta-analysis aimed to synthesize the available evidence on the association between thyroid status (dysfunction vs. euthyroid) and survival outcomes in HNC patients. METHODS: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Web of Science, Cochrane Library, Embase and Scopus were searched (January 2000-October 2024) for studies comparing survival outcomes (primarily Overall Survival) in adult HNC patients with thyroid dysfunction versus euthyroid patients. Two reviewers independently selected studies and extracted relevant data. The risk of bias for included studies was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the Cochrane Risk of Bias 2 (RoB2) tool for randomized controlled trials. Hazard ratios (HRs) with 95% confidence intervals (CIs) comparing survival were pooled using both fixed-effect (common-effect) and random-effects (REML) models. Heterogeneity across studies was assessed using the I² statistic and Cochran's Q test. Statistical analyses were performed using R with the meta package. RESULTS: Six studies met the inclusion criteria for systematic review. Four of these studies, encompassing 671 participants, reported sufficient data (Hazard Ratios for Overall Survival) for meta-analysis. The fixed-effect model yielded a pooled HR of 0.99 (95% CI: 0.98, 1.00; p = 0.0013). However, significant heterogeneity was observed (I² = 81.5%, p = 0.0010). Consequently, the random-effects model, deemed more appropriate, yielded a pooled HR of 1.45 (95% CI: 0.66, 3.19; p = 0.3601), indicating no statistically significant association between thyroid status and overall survival in HNC patients. The estimated between-study variance (τ²) was 0.53. CONCLUSION: This meta-analysis revealed substantial heterogeneity among studies investigating the impact of thyroid status on HNC survival. When accounting for this heterogeneity using a random-effects model, no significant association was found. The findings highlight the need for further research with larger sample sizes, standardized definitions of thyroid dysfunction, consistent reporting of adjusted effect estimates, and exploration of heterogeneity sources. TRIAL REGISTRATION: CRD42024535167.