Abstract
Relevance: Saliva is a promising non-invasive biological matrix for detecting tumor-associated changes. However, most reported salivary biomarkers and spectroscopic signatures have been obtained from patients with clinically established disease rather than from truly preclinical settings.The study aimed to summarize the biological mechanisms by which tumors may generate salivary signals and to evaluate the potential of attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and surface-enhanced Raman spectroscopy (SERS) for early cancer detection.Materials and Methods: A narrative review was conducted using a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science. Studies addressing salivary spectral profiles in malignant and precancerous conditions, extracellular vesicles, biomarkers, preanalytical factors, instrumental variability, and validation issues were analyzed.Results: Across different cancer sites, salivary spectral changes have been associated with proteins, lipids, carbohydrates, nucleic acids, phosphate-containing compounds, and extracellular vesicles. The strongest evidence has been reported for oral and oropharyngeal cancers, with additional data available for lung, breast, prostate, gastric, and other malignancies. Nevertheless, interpreting these signatures remains challenging because factors like saliva collection and processing protocols, analytical platforms, substrate effects, data preprocessing, smoking status, and oral inflammatory conditions strongly influence spectral patterns.Conclusion: Saliva-based vibrational spectroscopy is a promising approach for non-invasive cancer diagnostics, but it is not yet ready for routine early detection or population screening. Clinical translation requires standardized preanalytical protocols, external model validation, multicenter reproducibility studies, and prospective validation in preclinical cohorts.