The dual oncogenic and protective roles of hashimoto’s thyroiditis in papillary thyroid carcinoma: a cohort-based meta-analysis

BACKGROUND: The clinical impact of Hashimoto’s thyroiditis (HT) in papillary thyroid carcinoma (PTC) remains controversial. HT has been implicated in multifocal tumorigenesis but also linked to more favorable tumor biology. This meta-analysis aimed to clarify their association. METHODS: This cohort-based meta-analysis followed PRISMA guidelines and was registered on PROSPERO (CRD420251138031). PubMed, EMBASE, Cochrane Library, and Web of Science were searched for studies comparing PTC patients with and without coexisting HT. Primary outcomes included multifocality, bilaterality, capsular invasion, vascular invasion, extrathyroidal extension, lymph node metastasis, distant metastasis, recurrence, and mortality. Secondary outcomes included BRAF V600E mutation and radioactive iodine therapy. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Subgroup, sensitivity, and meta-regression analyses were conducted. RESULTS: Forty-one studies involving 67,901 patients were included. HT was associated with increased risks of multifocality (OR = 1.13) and bilaterality (OR = 1.20), alongside reduced risks of extrathyroidal extension (OR = 0.85), capsular invasion (OR = 0.73), central lymph node metastasis (OR = 0.75), distant metastasis (OR = 0.33), and recurrence (OR = 0.74). No significant differences were found for vascular invasion, lateral lymph node involvement, mortality, or radioactive iodine use. HT was significantly associated with a reduced frequency of BRAF V600E mutation (OR = 0.55), especially in patients over 45. CONCLUSION: HT demonstrates a dual role in PTC, promoting multifocality while attenuating aggressiveness and adverse outcomes. Incorporating HT status into preoperative evaluation may enhance individualized risk stratification and guide surgical and adjuvant decision-making.