Saliva holds the key: The emergence of saliva-based tests in oral cancer detection.

In the realm of cancer diagnostics, the emergence of saliva-based tests represents a revolutionary step forward, particularly in oral cancer detection. Traditionally, diagnosing oral cancer relied heavily on invasive procedures like biopsies, often uncomfortable for patients and potentially delaying detection. Despite advancements in surgical and therapeutic methods, along with improved access to clinical examinations, early warning signs, and symptoms, patients frequently miss the chance for timely diagnosis and treatment, leading to delay in treatment and thus poor survival rates.

However, the inception  of saliva-based tests offers a non-invasive, convenient, and potentially more accessible avenue for early oral cancer detection [1]. This blog post delves into the significance of saliva in cancer detection, the science behind saliva-based tests, and the implications of this emerging technology in the fight against oral cancer.

Oral cancer: Exploring the quiet menace

Oral cancer refers to a type of cancer that develops in the tissues of the mouth , encompassing areas such as the lips, tongue, gums, inside of the cheek and palate,. It can also affect the salivary glands, throat, and the back of the mouth. Typically, oral cancer begins with non-healing lesions or sores, presenting as growths, lumps, or patches in varied colors from white to red within the mouth.

Major risk factors for oral cancer include tobacco use (smoking, chewing), heavy alcohol consumption, human papillomavirus (HPV) infection, and excessive sun exposure to the lips. Early detection of oral cancer is crucial to enhance the success rate of treatment, which may include surgery, radiation therapy, chemotherapy, or a combination of these approaches [1,2].

The significance of saliva in oral cancer detection

Saliva, often overlooked in medical diagnostics, is a complex biological fluid containing a diverse array of biomarkers that mirror the body's physiological state. Within saliva, researchers have pinpointed various molecules—proteins, nucleic acids, metabolites—that act as disease indicators. Saliva has a lot of potential as a most convenient non-invasive diagnostic fluid and has huge advantages over other biological samples such as blood, smears, and tissue biopsies which include easy to collect, non-invasive, safe, easy to preserve, and contains adequate quantity of genetic materials. The simplicity of saliva collection makes it especially attractive for large-scale screening programs, where accessibility and patient compliance are pivotal.

In the context of oral cancer, saliva harbors specific biomarkers associated with the presence and progression of malignant lesions in the oral cavity. Salivary diagnostics can also help to detect oral infections, oral microbiome, metabolites, cytokines, immunoglobulins, hormones, mucins, growth factors, inhibitors, enzymes, gene mutations, epigenetic alterations, non-coding RNAs and salivary exosomes and exosomal miRNAs. Thus, saliva is considered a therapeutically invaluable bio-fluid, offering invaluable insights into diagnosis, prognosis, and therapeutic targets for oral cancer treatment and monitoring [1,2].

Emerging trends in early oral cancer detection using saliva biomarkers

Saliva, once overlooked as a diagnostic tool, is emerging as a promising avenue for early detection of oral cancer. Researchers are intensifying their efforts to pinpoint and validate specific biomarkers present in saliva that could serve as indicators of cancerous lesions. Saliva-based tests for oral cancer rely on the detection of specific biomarkers indicative of disease presence or progression. These biomarkers encompass proteins, DNA mutations, RNA transcripts, and metabolites that are shed into the saliva either by tumor cells or the body's response to the presence of cancer [1,2].

Here are the latest research findings and notable salivary biomarkers for oral cancer:

• Genetic Markers: Mutations in DNA and RNA within tumor cells can be identified in saliva, providing a method to detect specific types of oral cancer, such as HPV-associated oropharyngeal cancers. Among the extensively studied biomarkers for oral cancer detection is HPV DNA, detectable through saliva-based tests. This detection offers valuable insights into cancer origin and assists in treatment decisions.

• Protein-based Biomarkers: Protein anomalies, including matrix metalloproteinase-1 (MMP-1), MMP-9, IL-8, and Cytokeratin-19, are studied for their potential to distinguish healthy from cancerous states. Oral squamous cell carcinoma (OSCC) cases often show elevated levels of salivary soluble CD44, aiding in cancer detection. Additionally, Cyfra21-1, cancer antigen 125, ErbB2 (a transmembrane glycoprotein), and tissue polypeptide antigen are enhanced in OSCC saliva. Salivary p53-AAb positivity is higher in OSCC patients, especially those with tobacco use, compared to healthy individuals.

• MicroRNAs (miRNAs): These tiny molecules, crucial for gene regulation, exhibit altered expression patterns in cancer and can be identified in saliva, providing valuable insights into disease progression. Variations in miRNA levels could influence the pathogenesis of OSCC. Salivary miRNA-21 and miRNA-184 hold potential for the early detection of OSCC and oral potentially malignant disorders. Additionally, saliva serves as a medium for identifying neoplastic changes in oral mucosa.

• Other Biomarkers: Metabolites, exosomes, and the composition of the oral microbiome are also under investigation for their potential role in oral cancer detection via saliva analysis [1–5].

Implications of saliva-based tests in oral cancer detection

The emergence of saliva-based tests in oral cancer detection presents a promising avenue for enhancing patient outcomes through early detection and intervention. These tests facilitate non-invasive, cost-effective, and easily accessible screening methods, potentially revolutionizing the landscape of oral cancer diagnosis and management. Saliva-based tests offer the opportunity for routine screening of high-risk populations, including individuals with a history of tobacco or alcohol use, and those with a family history of oral cancer.

Moreover, saliva-based tests offer additional benefits beyond the initial diagnosis. They hold the potential for developing personalized treatment strategies based on tumor characteristics identified in saliva samples. By continuously monitoring changes in salivary biomarker levels over time, clinicians can evaluate the efficacy of treatment modalities and adapt therapeutic strategies as needed. This personalized approach to cancer management can enhance patient care, optimize treatment outcomes, and reduce the likelihood of disease recurrence [1–4].

Can saliva tests lead the way?

Saliva-based tests are revolutionizing oral cancer detection, offering a non-invasive, accessible, and potentially life-saving alternative to traditional methods. By harnessing the wealth of information within saliva, researchers are identifying specific biomarkers that can signal the presence of cancer even in its early stages. This has the potential to significantly improve treatment outcomes and patient survival rates. While significant progress has been made, continued research and development are crucial to refine existing tests, discover new biomarkers, and ensure widespread accessibility.

References

1. Kumar, P. et al. 'Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer'. Transl Oncol. (2024) 40, 101827. DOI: 10.1016/j.tranon.2023.101827.

2. Umapathy, V.R. et al. 'Review Insights on Salivary Proteomics Biomarkers in Oral Cancer Detection and Diagnosis'. Molecules. (2023) 28(13), 5283. DOI: 10.3390/molecules28135283.

3. Jayarajkumar, S. et al. 'Assessment of salivary levels of ErbB2 in oral squamous cell carcinoma'. J Oral Maxillofac Pathol. (2023) 27(4), 777. DOI: 10.4103/jomfp.jomfp_114_23.

4. Garg, A. et al. 'Evaluation of Diagnostic Significance of Salivary miRNA-184 and miRNA-21 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders'. Head Neck Pathol. (2023) 17(4), 961–968. DOI: 10.1007/s12105-023-01600-7.

5 Sreelatha, S.V. et al. 'Assaying of p53 Autoantibodies in saliva for the detection of oral squamous cell carcinoma. A road not taken'. Indian J Cancer. (2023). DOI: 10.4103/ijc.IJC_870_20.