Decoding salivary gland tumor complexities through omics integration: A systematic analysis across the 21st century

Salivary gland tumors (SGTs) are rare and biologically heterogeneous neoplasms for which conventional histopathological and single-platform molecular analyses have provided limited insights into disease mechanisms and therapeutic vulnerabilities. Advances in high-throughput technologies now enable integration of different molecular layers, offering unprecedented resolution of tumor complexities. We conducted a systematic review of studies published between 2001 and 2026 that applied multi-omics integration to human SGTs, requiring the combination of at least two omics layers. Seventy-eight studies met the inclusion criteria, most of which were observational (65.4%) and conducted in high-income countries (98.7%). Research were predominantly focused on malignant tumors (85.9%), particularly adenoid cystic carcinoma (38.5%), and frequently relied on formalin-fixed paraffin-embedded samples (55.7%). Genomic and transcriptomic integration was the most commonly used strategy (74.4%), typically supported by immunohistochemistry (61.5%) and in situ hybridization (38.5%) for biological validation. Overall, multi-omics studies have advanced molecular classification in selected tumor types, enabled the generation and validation of biologically faithful in vitro and in vivo models, identified prognostically relevant subgroups, and revealed actionable molecular vulnerabilities. However, despite these advances, clinical translation remains limited. Future progress will depend on prospective, clinically integrated, and functionally validated multi-omics studies to enable meaningful implementation of precision medicine for SGTs.