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Review

Graphene-Based Electrochemical Biosensors for Oral Cancer Detection: Advances, Challenges, and Future Prospects-A Systematic Review

Jeetendra Kumar Gupta1, Priyanga Jaganath2, Ramenani Hari Babu3, Konatham Teja Kumar Reddy4, Venkata Lakshamana Sagar Dantinapalli5, Selvaraja Elumalai6, Thota Chandrasekhar Yadav7, Venkateswara Rao Rachumallu8, Prabakaran Sankar9, Jaya Shree Srinivasan9, Lokeshvar Ravikumar9★★ Corresponding author

  1. 1Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, INDIA.
  2. 2Department of Pharmacology, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai, Tamil Nadu, INDIA.
  3. 3Department of Pharmacy Practice, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, INDIA.
  4. 4Department of Pharmaceutical Analysis, Malla Reddy Institute of Pharmaceutical Sciences, Malla Reddy Vishwavidyapeeth (Deemed to be University), Secunderabad, Telangana, INDIA.
  5. 5Department of Chemistry, Raffles University, Neemrana, Alwar, Rajasthan, INDIA.
  6. 6Department of Chemistry, School of Basic and Applied Sciences, Raffles University, Neemrana, Rajasthan, INDIA.
  7. 7Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Andhra Pradesh, INDIA.
  8. 8Department of Pharmacology and Pharmacokinetics, Quest Life Sciences Pvt. Ltd., Research Foundation in Chennai, Chennai, Tamil Nadu, INDIA.
  9. 9Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Saveetha Nagar, Thandalam, Chennai, Tamil Nadu, INDIA.

CORRESPONDENCE

Lokeshvar Ravikumar

Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Saveetha Nagar, Thandalam, Chennai-602105, Tamil Nadu, INDIA.

lokeshvarr.scop@saveetha.com

ORCID: 0000-0001-6869-3446

Received: 03-11-2025; Revised: 24-12-2025; Accepted: 16-02-2026.

Volume 18, Issue 1 · pp. 70–79 · PUBLISHED Jan-Mar 2026 · DOI: 10.5530/jyp.20260170

View on JYP original site ↗

ABSTRACT

Graphene-based electrochemical biosensors are emerging as powerful diagnostic platforms for early, non-invasive detection of oral cancer. This review critically evaluates recent advances in graphene-enabled salivary biosensing, emphasizing the role of graphene’s unique physicochemical properties-such as large surface area, conductivity, and biocompatibility-in improving sensitivity and specificity. A comprehensive literature search was conducted using PubMed, Scopus, and ScienceDirect databases to identify peer-reviewed studies from 2010-2025 on graphene-based electrochemical biosensors for salivary biomarker detection. The findings indicate that graphene-integrated systems significantly enhance electrochemical detection techniques including voltammetry, impedance spectroscopy, and field-effect transistors. Major challenges remain in clinical translation, including reproducibility, scalability, and regulatory approval. Future perspectives involve integrating these biosensors with artificial intelligence, microfluidics, and telemedicine platforms to enable affordable, portable, and real-time oral cancer diagnostics. Overall, graphene-based biosensors represent a transformative step toward personalized, point-of-care cancer management.

KEYWORDS

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FULL TEXT

INTRODUCTION

Early detection is crucial for improving survival and treatment outcomes in cancer, highlighting the need for rapid, sensitive, and non-invasive diagnostic tools. Biosensors have emerged as promising platforms due to their ability to detect cancer biomarkers with high specificity, providing real-time insights into disease presence, progression, and prognosis. Oral Squamous Cell Carcinoma (OSCC) remains a major global health issue, with over 350,000 new cases annually, especially in regions with prevalent tobacco, alcohol, and betel quid use. Conventional diagnostics, such as biopsies and imaging, are invasive, costly, and infrastructure-dependent, limiting early detection (Fadaka et al., 2019). Saliva has emerged as an attractive biofluid for diagnostics due to its non-invasive collection, affordability, and rich molecular content, including DNA, RNA, proteins, and metabolites. Graphene-based electrochemical biosensors have gained attention for salivary diagnostics, offering exceptional sensitivity and selectivity owing to graphene’s two-dimensional structure, high conductivity, large surface area, and mechanical strength (Cheng et al., 2017). Electrochemical methods like amperometry, voltammetry, and impedance spectroscopy further enhance detection accuracy and speed. Despite laboratory successes, clinical translation faces challenges including biocompatibility, reproducibility, stability, and scalability. This review provides a critical synthesis of graphene-based salivary biosensors for oral cancer, examining design innovations, analytical performance, translational barriers, and future directions to bridge the gap between experimental research and clinical application (Akashanand et al., 2024). A systematic literature search was conducted using PubMed, Scopus, and ScienceDirect databases, and the study selection process is illustrated in Figure 1.

Figure 1: Study selection process.

Key Advantages of Saliva as a Diagnostic Fluid

Saliva has become a powerful medium for non-invasive diagnostics due to its accessibility, ease of collection, and reduced discomfort, cost, and infection risk compared to blood sampling. It is ideal for large-scale screenings and repeated sampling in longitudinal studies. Biochemically, saliva contains proteins, DNA, RNA, metabolites, and exosomes that reflect both local and systemic physiological states, with fewer interfering substances like clotting factors, facilitating sample handling (Yoshizawa et al., 2013). Its proximity to oral tissues allows early detection of neoplastic changes, making it highly relevant for oral cancer screening. Combined with multiplex biomarker detection and compatibility with point-of-care devices, saliva offers a highly effective matrix for future personalized healthcare applications (Bhattacharjya et al., 2025).

Graphene: A Multifunctional Platform for Advanced Biosensing

Graphene, a single layer of carbon atoms in a two-dimensional honeycomb lattice, has transformed nanomaterials due to its exceptional electrical, mechanical, and thermal properties (Mahalakshmi et al., 2025). With a thickness of ~0.35 nm and interatomic bond length of 1.42 Å, its unique band structure enables efficient electron transport, high charge carrier mobility, and minimal energy loss, ideal for electronic and biosensing applications. Its biocompatibility, especially in forms like reduced Graphene Oxide (rGO), ensures minimal cytotoxicity, supports cell growth, and reduces inflammation, making it safe for oral cavity applications (Kaur et al., 2018). Slow physiological degradation further contributes to long-term stability. Graphene is produced via top-down methods (mechanical exfoliation, chemical reduction) and bottom-up methods (chemical vapor deposition, epitaxial growth), with CVD offering high-quality, scalable fabrication. Solution-based techniques like layer-by-layer deposition and Langmuir-Blodgett assembly allow fine-tuning for specific biosensor architectures (Nandhini and Karthikeyan, 2024). In biosensors, graphene’s high surface area and superior electron transfer enable detection of ultra-low analyte concentrations. Functionalization with antibodies, aptamers, or enzymes enhances specificity and reduces interference, generating measurable electrical signals for rapid biomarker quantification (Goldoni et al., 2021). Graphene’s mechanical flexibility supports wearable and portable diagnostics, particularly in biofluids like saliva. Compared to silicon, zinc, or gold, it offers greater chemical stability, reusability, and adaptability in complex biological environments. Scalable production and affordability position graphene as a foundation for next-generation salivary biosensors for early disease detection and point-of-care applications (Neumaier et al., 2019).

Graphene Synthesis and Surface Modifications

The performance of graphene-based biosensors is closely linked to the synthesis method and subsequent surface modifications. Two common approaches for graphene synthesis include the Hummers’ method for chemical oxidation of graphite to produce Graphene Oxide (GO) and Chemical Vapor Deposition (CVD) to create high-quality graphene films suitable for large-area sensor fabrication. Surface modification plays a crucial role in enhancing biorecognition and signal stability (Ullah et al., 2020). Functional groups such as carboxyl, hydroxyl, and epoxy moieties can be introduced during or after synthesis, allowing for covalent or non-covalent immobilization of biological probes like antibodies, aptamers, or enzymes. Such modifications not only improve selectivity and sensitivity but also reduce nonspecific interactions. Innovations in graphene hybrid nanocomposites such as integrating metal nanoparticles, metal oxides, or conductive polymers further amplify signal output and offer tailored biocompatibility, making them well-suited for complex biofluids like saliva (Magne et al., 2022).

Salivary Biomarkers to Detect Oral Cancer

Saliva is emerging as a valuable diagnostic medium in oncology due to its rich molecular content, non-invasive collection, low interference, and suitability for repeated sampling. It contains DNA, mRNA, proteins, metabolites, and exosomes, reflecting tumor-associated molecular changes for early oral cancer detection (Kumar et al., 2021). Elevated cytokines (IL-6, IL-8, IL-1β), cancer antigens (Cyfra 21-1, CA 125), proteins (Mac-2 binding protein, profilin-1, CD59, catalase), and soluble CD44 show diagnostic potential as listed in Table 2. Dysregulated microRNAs and VEGF indicate early-stage disease, while MMP-9 and EGFR mark progression. Key DNA-based salivary biomarkers are summarized in Table 3. While important RNA biomarkers relevant to oral cancer are presented in Table 4. Challenges include low analyte levels, variability, biomolecule instability, and interference. Graphene-based biosensors overcome many of these issues via high surface area and enhanced sensitivity, enabling rapid, specific, and reliable salivary biomarker detection (Ullah et al., 2021).

Table 1: Comparative Overview of Nanomaterials Used in Biosensors.
NanomaterialAdvantagesLimitationsDiagnostic UseReferences
GrapheneHigh surface area, conductivity, flexible, biocompatibleAggregation; complex synthesisSalivary biomarker detection in oral cancer(Mahalakshmi et al., 2025c)
Gold NPsOptical features, easy functionalization, biocompatibleAggregation; costlyColorimetric/electrochemical biosensors(Kumalasari et al., 2024)
Carbon NanotubesConductive, stableLimited functionalization; potential toxicityElectrochemical cancer sensing(Karagianni et al., 2026)
SiliconTunable optical/electronic propertiesBrittle; less biocompatibleOptical biosensors(Mahalakshmi et al., 2025c)
Quantum DotsBright, tunable emissionToxicity; complex synthesisFluorescent biosensors(Tandale et al., 2021)
Metal OxidesCatalytic, cost-effectiveLower conductivityElectrochemical diagnostics(P. Kumar et al., 2024)
Table 2: Protein Biomarkers in Oral Cancer.
Sl. No.BiomarkerKey Properties and ApplicationsReferences
1CatalaseUsed in OSCC diagnosis(Ravikumar and Velmurugan, 2024)
2CD44High diagnostic/prognostic accuracy
3CD59Overexpressed in saliva; T-cell activation
4Cyfra-21-1, TPA, CA125Salivary markers; indicate early chemo response(Ilhan et al., 2020)
5Defensin-1Elevated; improves early detection
6IL-1αRegulates inflammation and angiogenesis
7IL-1βIncreased in oral cancer; modulates immune/inflammatory response
8IL-6Proangiogenic/inflammatory; aids early diagnosis and prognosis
9IL-8Elevated in oral cancer; also relevant in periimplantitis(Hao et al., 2019)
10InvolucrinDifferential expression in OSCC vs healthy tissue
11M2BPOverexpressed; involved in cell adhesion/matrix interaction
12MMP-11Invasive/metastatic; poor prognosis marker
13MMP-2Promotes metastasis and vascular growth
14MMP-8Elevated in saliva; useful in periodontal assessment
15MMP-9Supports angiogenesis; dysplasia-to-cancer transition(Mahalakshmi et al., 2025d)
16MRP14Regulates leukocyte movement and inflammation
17ProfilinVaried levels between OSCC and healthy controls
18S100A12Differential expression in oral cancer
19Salivary Alpha AmylasePotential diagnostic marker; breaks down starch
20TGF-βUnchanged levels; limited diagnostic value
21TNF-αStimulates proliferation, inhibits apoptosis, induces inflammation(Mesrati et al., 2021)
Table 3: DNA biomarkers.
Sl. No.BiomarkerKey Properties and ApplicationsReferences
18-OHdGReduced levels in saliva(S. Kumar et al., 2019)
2Chromosomal regions 3p, 9q, 13q, 17pLinked to early oral cancer
3Cyclin D1 (CCND1)Amplification/overexpression; poor prognosis
4p27 (CDKN1B), TP63, TP73Allelic loss on 9p
5DAPK1Apoptosis regulator; often hypermethylated
6DCCNetrin receptor; present in saliva of patients
7EDN1Tumor-promoting G-protein receptor(Wu et al., 2018)
8Ki67Elevated in saliva; proliferation/metastasis marker
9KIF1AInvolved in apoptosis and DNA repair
10LDHOverexpressed in saliva; key in anaerobic glycolysis
11LINE-1Hypomethylated in oral cancer
12MINT31Regulates calcium channels
13RASSF1αTumor suppressor; inhibits growth via RAS(Guo et al., 2023)
14RARβ, FHIT, p15, TIMP3, APCFrequently methylated
15TIMP1Detected in saliva; prognosis marker
16TIMP3Immune response and T-cell recognition
17TP53DNA repair and apoptosis; LOH linked to cancer
18p16INK4ASonic hedgehog signaling pathway
19p16INK4A, MGMT, DAPK1, GSTP1Frequently methylated in saliva
20VEGF, BCL-2, Claudin 4, YAP1, METPredicts radio-resistance in OSCC(Shpitzer et al., 2009)
Table 4: RNA Biomarkers in Oral Cancer.
Sl. No.RNA BiomarkerKey Properties and ApplicationsReferences
1circRNA-5Saliva/serum; promotes tumor growth/metastasis(Fan et al., 2020)
2DYRK1ADifferentiates oral cancer from normal tissue
3H3F3ANucleosome maintenance; marker of proliferation
4IL-1βSaliva; regulates inflammation, apoptosis, proliferation; diagnostic marker
5IL-8Saliva; angiogenesis, immune modulation, cell cycle control(Lee et al., 2011)
6lncRNALinked to metastasis and progression
7miRNA-125aSaliva; suppresses cell growth
8miRNA-133Inhibits tumor progression via Bcl2/RhoA
9miRNA-145Promotes apoptosis; regulates KRAS, c-Myc, DFF45(Jung et al., 2021)
10miRNA-184Enhances growth; suppresses apoptosis via c-Myc
11miRNA-200aTumor suppressor; early metastasis indicator
12miRNA-21Saliva; promotes growth/invasion via Wnt/β-catenin targeting DKK2
13miRNA-31Promotes proliferation/metastasis; monitors recurrence
14S100PDifferential in OSCC; regulates cell cycle/differentiation(Kaur et al., 2022)

Electrochemical Graphene Biosensors for Salivary Biomarkers in Oral Cancer

The emergence of electrochemical biosensors has transformed disease diagnostics by enabling rapid, sensitive, and cost-effective detection of clinically relevant biomarkers. These sensors operate by converting specific biochemical interactions into quantifiable electrochemical signals, offering a robust platform for detecting disease markers, including those associated with oral cancer. In the context of saliva-based diagnostics, graphene plays a central role due to its exceptional conductive and surface properties, making it highly responsive to minute biological changes. Various electrochemical detection techniques have been adapted to work with graphene-based platforms for enhanced sensitivity and selectivity as summarized in Table 1, and representative fabrication and electrochemical measurement strategies for graphene-based immunosensors are illustrated in Figure 3.

Figure 2: Illustrates the structure and function of graphene-based electrochemical biosensors designed for detecting salivary biomarkers associated with oral cancer (Mahalakshmi et al., 2025b).
Figure 3: Presents a schematic overview showing (a) the fabrication steps of the Anti-IL8/ZnO-rGO/ITO immunosensor and (b) the electrochemical setup employed to perform electro-analytical measurements with the fabricated sensor (Mahalakshmi et al., 2025e).

Cyclic Voltammetry (CV)

CV is one of the most widely employed techniques to evaluate redox behaviour of biomolecules. It applies a cyclic potential sweep to the sensor's electrode, recording current changes that reflect electrochemical activity. Graphene's high conductivity and large surface area enhance electron transfer, making it ideal for detecting low-abundance biomarkers such as Cyfra 21-1 and IL-8 in saliva. For instance, a CV biosensor based on ZrO₂-Reduced Graphene Oxide (RGO) demonstrated high performance in detecting Cyfra 21-1, with a wide dynamic range and low detection limits, supported by ELISA validation. Similarly, ZnO-rGO composites have been used for IL-8 detection, showing excellent response in clinical saliva samples (Karim, 2021).

Differential Pulse Voltammetry (DPV)

DPV provides high-resolution data by applying pulsed voltage ramps and measuring resulting currents, enabling detection of biomarkers in complex media. Gold nanoparticles combined with RGO (AuNPs-rGO) have been used to develop immunosensors for IL-8, offering excellent stability, specificity, and reusability. Another design using cerium oxide-RGO composites has successfully detected Cyfra 21-1 with picogram-level sensitivity and negligible cross-reactivity.

Electrochemical Impedance Spectroscopy (EIS)

EIS detects changes in electrical impedance caused by biomolecular interactions at the sensor interface. Label-free EIS sensors incorporating RGO have shown accurate quantification of Carcinoembryonic Antigen (CEA) and Cyfra 21-1 in saliva, effectively distinguishing healthy individuals from OSCC patients using portable prototypes. The impedance shifts due to antigen-antibody binding lead to quantifiable electrical signals, making EIS particularly valuable for point-of-care testing (Verma et al., 2023).

Field-Effect Transistor (FET) Sensors

Graphene-based FET sensors offer ultra-fast detection by measuring current changes in a semiconductor channel upon biomarker binding. Aptamer-functionalized graphene FETs have been developed to detect IL-6 in saliva, demonstrating detection within seven minutes and high sensitivity. These sensors are also being adapted for handheld devices connected to mobile platforms, integrating diagnostics with cloud-based data analysis (Verma et al., 2017).

Amperometric Sensors

Amperometry involves measuring current at a constant potential, offering real-time monitoring of electroactive species. A self-reporting biosensor composed of graphene oxide, gadolinium hexacyanoferrate, and gold nanoparticles achieved sensitive detection of Cyfra 21-1 without needing external redox mediators, providing a direct and simplified detection system suitable for clinical use.

Chronoamperometry (CA)

CA sensors step the voltage at fixed intervals and track current over time to monitor redox reactions. A graphene oxide-aptamer sensor was designed to detect TNF-α, showing high sensitivity in the picogram range. The molecular beacon-based electrochemical detection strategy for TNF-α is depicted in Figure 4. This system enables longitudinal monitoring of inflammatory markers in oral cancer patients (Devaraji and Ravikumar, 2024).

Figure 4: Shows an electrochemical molecular beacon-based biosensor designed for detecting TNF-α in saliva, highlighting its potential use in early diagnosis of oral cancer (Mahalakshmi et al., 2025e).

Photoelectrochemical (PEC) Biosensors

PEC combines optical and electrochemical principles for enhanced sensitivity. A novel PEC sensor using graphene oxide, silver nanoclusters, and hemin detected the oral cancer-associated gene ORAOV1 at femtomolar levels, demonstrating ultra-sensitive diagnostics. Graphene-powered electrochemical techniques enable rapid, specific detection of salivary biomarkers and can be adapted for wearable or portable formats, supporting early oral cancer diagnosis and treatment monitoring, especially in decentralized or resource-limited settings (Ahmad et al., 2023). Challenges of Graphene-Based Electrochemical Biosensors for Salivary Biomarker Analysis in Oral Cancer.Graphene-based electrochemical biosensors hold promise for non-invasive oral cancer detection, but clinical use remains challenging. Patient heterogeneity, low-abundance salivary biomarkers, and saliva’s complex composition can compromise accuracy. Functionalizing graphene for selective binding is difficult, and unstable modifications may cause signal drift and poor reproducibility. Additional hurdles include salivary variability, scalable production, batch consistency, long-term stability, affordability, and point-of-care compatibility. Clinical deployment requires multidisciplinary expertise, standardized validation, robust trials, and regulatory guidance. Future research should focus on optimizing surface functionalization, enhancing sensor stability in physiological conditions, and fostering cross-disciplinary collaboration. Standardized testing across diverse populations is critical to ensure reliability and enable real-world application of graphene-based biosensors in oral cancer diagnostics (Pirzada and Altintas, 2019).

Clinical Validation and Regulatory Considerations

Despite promising laboratory performance, translating graphene-based biosensors into clinical diagnostics requires rigorous validation. This includes clinical trials, reproducibility studies, and comparison with gold-standard diagnostic tools. Standardization of sample collection, biomarker thresholds, and analytical protocols is essential for ensuring consistency across patient populations. The overall structure and working principle of graphene-based electrochemical biosensors for salivary biomarker detection are illustrated in Figure 2. Regulatory hurdles remain a significant barrier. For clinical approval, biosensors must meet stringent criteria set by organizations such as the U.S. FDA, CE, or ISO standards, covering aspects like safety, accuracy, and reliability. Addressing these requirements will involve collaborative efforts across academia, industry, and regulatory bodies to accelerate the bench-to-bedside transition (Song et al., 2025).

Futuristic Approaches for Graphene-Based Electrochemical Biosensors for Salivary Biomarker Analysis in Oral Cancer

Graphene-based electrochemical biosensors offer personalized, non-invasive oral cancer diagnostics. Integration with AI/ML enables real-time analysis, biomarker pattern recognition, and personalized treatment guidance. Future multiplexed platforms can detect multiple salivary biomarkers, providing precise diagnosis, staging, and prognosis. Affordable, portable, and wearable devices-supported by microfluidics, lab-on-chip systems, and telemedicine-allow rapid, continuous monitoring of nucleic acids, proteins, and metabolic or ionic markers, revealing tumor and systemic health insights. Clinical adoption requires validation, regulatory approval, standardization, and ethical compliance. The convergence of graphene nanotechnology, biosensor design, and digital health promises accurate, accessible, and proactive oral cancer diagnostics for individualized patient care (Daweshar et al., 2024).

Integration with mHealth and Wearable Technologies

The future of graphene-based biosensing extends beyond standalone diagnostics to integrated mobile health (mHealth) platforms. By coupling biosensors with smartphones, cloud computing, and wireless communication modules, real-time monitoring of salivary biomarkers becomes possible. These systems can automatically transmit diagnostic data to clinicians or centralized databases, supporting rapid decision-making and personalized care. Furthermore, advances in wearable biosensors, such as graphene-coated mouthguards, dental patches, or intraoral strips, could enable continuous, real-time analysis of salivary components. These innovations can transform oral cancer management from periodic check-ups to dynamic, patient-driven health monitoring Mishra et al., 2024).

CONCLUSION AND FUTURISTIC OUTLOOK

Graphene-based electrochemical biosensors are revolutionizing oral cancer diagnostics by offering sensitive, selective, and non-invasive salivary detection. Their high surface area, conductivity, and mechanical strength allow ultra-low biomarker detection, supporting early-stage diagnosis and improved prognosis. These sensors enable real-time, low-cost, point-of-care testing, increasing accessibility and accuracy. Current challenges include stable surface functionalization, reproducible fabrication, scalable production, and limited single-analyte detection. The future lies in multiplexed platforms capable of simultaneously detecting multiple salivary biomarkers, integrated with microfluidics, lab-on-chip systems, and AI-driven analytics. Coupled with telemedicine, they can facilitate remote monitoring, personalized disease management, and broader healthcare access. Ongoing research to overcome technical and regulatory barriers will be key to clinical translation. Graphene-based biosensors have the potential to redefine oral cancer detection, enabling earlier diagnosis, precise monitoring, and improved patient outcomes, forming the backbone of next-generation diagnostic tools (Khan et al., 2023).

REFERENCES

As published

Showing references and in-text citations exactly as published.

  1. 1.Ahmad, M.; Hasan, M.; Tarannum, N.; Hasan, M.; Ahmed, S.. Recent advances in optical and photoelectrochemical nanobiosensor technology for cancer biomarker detection. In Biosensors and Bioelectronics. 2023;X(14):Article 100375. https://doi.org/10.1016/j.biosx.2023.100375DOIGOOGLE SCHOLAR
  2. 2.Akashanand, Q. S.; Zahiruddin, Q. S.; Jena, D.; Ballal, S.; Kumar, S.; Bhat, M. et al. Burden of oral cancer and associated risk factors at national and state levels: A systematic analysis from the global burden of disease in India, 1990–2021. Oral Oncology. 2024;159:Article 107063. https://doi.org/10.1016/J.ORALONCOLOGY.2024.107063DOIGOOGLE SCHOLAR
  3. 3.Bhattacharjya, T.; Nalepa, M.-A.; Dědek, I.; Jakubec, P.; Panáček, D.; Otyepka, M.. Recent advances in graphene-based electrochemical biosensors for major non-communicable diseases. Current Opinion in Electrochemistry. 2025;53:Article 101737. https://doi.org/10.1016/J.COELEC.2025.101737DOIGOOGLE SCHOLAR
  4. 4.Cheng, F.; Hong, H.; Yang, S.; Wei, Y.. Individualized network-based drug repositioning infrastructure for precision oncology in the Panomics era. Briefings in Bioinformatics. 2017;18(4):682–697. https://doi.org/10.1093/bib/bbw051DOIGOOGLE SCHOLAR
  5. 5.Daweshar, E.; Pankaj; Mewada, R.; Kumar, S.. A comprehensive review on quantification of various biomarkers for the detection of oral carcinoma via electrochemical biosensors. Microchemical Journal. 2024;207(Article 111741.). https://doi.org/10.1016/J.MICROC.2024.111741DOIGOOGLE SCHOLAR
  6. 6.Devaraji, M.; Ravikumar, L.. The role of liquid biopsy in early detection and monitoring of oral cancer. Oral Oncology Reports. 2024;11:Article 100618. https://doi.org/10.1016/J.OOR.2024.100618DOIGOOGLE SCHOLAR
  7. 7.Fadaka, A. O.; Pretorius, A.; Klein, A.. Biomarkers for stratification in colorectal cancer: MicroRNAs. In Cancer Control. 2019;26(1):Article 1073274819862784. https://doi.org/10.1177/1073274819862784DOIGOOGLE SCHOLAR
  8. 8.Fan, H.-Y.; Jiang, J.; Tang, Y.-J.; Liang, X.-H.; Tang, Y.-L.. CircRNAs: A new chapter in oral squamous cell carcinoma biology. In OncoTargets and Therapy. 2020;13:9071–9083. https://doi.org/10.2147/OTT.S263655DOIGOOGLE SCHOLAR
  9. 9.Goldoni, R.; Farronato, M.; Connelly, S. T.; Tartaglia, G. M.; Yeo, W.-H.. Recent advances in graphene-based nanobiosensors for salivary biomarker detection. In Biosensors and Bioelectronics. 2021;171(Article 112723.). https://doi.org/10.1016/j.bios.2020.112723DOIGOOGLE SCHOLAR
  10. 10.Guo, Y.; Xu, T.; Chai, Y.; Chen, F.. TGF-β signaling in progression of oral cancer. In International Journal of Molecular Sciences. 2023;24(12):Article 10263. https://doi.org/10.3390/ijms241210263DOIGOOGLE SCHOLAR
  11. 11.Hao, Z.; Pan, Y.; Shao, W.; Lin, Q.; Zhao, X.. Graphene-based fully integrated portable nanosensing system for on-line detection of cytokine biomarkers in saliva. Biosensors and Bioelectronics. 2019;134:16–23. https://doi.org/10.1016/j.bios.2019.03.053DOIGOOGLE SCHOLAR
  12. 12.Hassn Mesrati, M. H.; Syafruddin, S. E.; Mohtar, M. A.; Syahir, A.. CD44: A multifunctional mediator of cancer progression. In Biomolecules. 2021;11(12):Article 1850. https://doi.org/10.3390/biom11121850DOIGOOGLE SCHOLAR
  13. 13.Ilhan, B.; Lin, K.; Guneri, P.; Wilder-Smith, P.. Improving oral cancer outcomes with imaging and artificial intelligence. Journal of Dental Research. 2020;99(3):241–248. https://doi.org/10.1177/0022034520902128DOIGOOGLE SCHOLAR
  14. 14.Jung, J. E.; Lee, J. Y.; Park, H. R.; Kang, J. W.; Kim, Y. H.; Lee, J. H.. MicroRNA-133 targets phosphodiesterase 1C in Drosophila and human oral cancer cells to regulate epithelial-mesenchymal transition. Journal of Cancer. 2021;12(17):5296–5309. https://doi.org/10.7150/jca.56138DOIGOOGLE SCHOLAR
  15. 15.Karagianni, A.; Tsierkezos, N. G.; Ntziouni, A.; Terrones, M.; Kordatos, K. V.. Carbon nanotubes as electrochemical sensors for neurotransmitters: Synthesis, doping, and applications. Carbon. 2026;246:Article 120832. https://doi.org/10.1016/J.CARBON.2025.120832DOIGOOGLE SCHOLAR
  16. 16.Karim, M. E.. Biosensors: Ethical, regulatory, and legal issues. Handbook of cell biosensors. Springer International Publishing.. 2021;679–705. https://doi.org/10.1007/978-3-030-23217-7_23DOIGOOGLE SCHOLAR
  17. 17.Kaur, J.; Jacobs, R.; Huang, Y.; Salvo, N.; Politis, C.. Salivary biomarkers for oral cancer and pre-cancer screening: A review. In Clinical Oral Investigations. 2018;22(2):633–640. https://doi.org/10.1007/s00784-018-2337-xDOIGOOGLE SCHOLAR
  18. 18.Kaur, J.; Preethi, M.; Srivastava, R.; Borse, V.. Role of IL-6 and IL-8 biomarkers for optical and electrochemical based point-of-care detection of oral cancer. Biosensors and Bioelectronics. 2022;X(11):Article 100212. https://doi.org/10.1016/j.biosx.2022.100212DOIGOOGLE SCHOLAR
  19. 19.Khan, A.; DeVoe, E.; Andreescu, S.. Carbon-based electrochemical biosensors as diagnostic platforms for connected decentralized healthcare. Sensors and Diagnostics. 2023;2(3):529–558. https://doi.org/10.1039/D2SD00226DDOIGOOGLE SCHOLAR
  20. 20.Kumalasari, M. R.; Alfanaar, R.; Andreani, A. S.. Gold nanoparticles (AuNPs): A versatile material for biosensor application. Talanta Open. 2024;9:Article 100327. https://doi.org/10.1016/J.TALO.2024.100327DOIGOOGLE SCHOLAR
  21. 21.Kumar, N.; Salehiyan, R.; Chauke, V.; Joseph Botlhoko, O.; Setshedi, K.; Scriba, M. et al. Top-down synthesis of graphene: A comprehensive review. In FlatChem. 2021;27:Article 100224. https://doi.org/10.1016/j.flatc.2021.100224DOIGOOGLE SCHOLAR
  22. 22.Kumar, P.; Rajan, R.; Upadhyaya, K.; Behl, G.; Xiang, X.-X.; Huo, P. et al. Metal oxide nanomaterials based electrochemical and optical biosensors for biomedical applications: Recent advances and future prospectives. Environmental Research. 2024;247:Article 118002. https://doi.org/10.1016/J.ENVRES.2023.118002DOIGOOGLE SCHOLAR
  23. 23.Kumar, S.; Panwar, S.; Kumar, S.; Augustine, S.; Malhotra, B. D.. Biofunctionalized nanostructured yttria modified non-invasive impedometric biosensor for efficient detection of oral cancer. Nanomaterials. 2019;9(9):Article 1190. https://doi.org/10.3390/nano9091190DOIGOOGLE SCHOLAR
  24. 24.Lee, Y.-H.; Zhou, H.; Reiss, J. K.; Yan, X.; Zhang, L.; Chia, D. et al. Direct saliva transcriptome analysis. Clinical Chemistry. 2011;57(9):1295–1302. https://doi.org/10.1373/clinchem.2010.159210DOIGOOGLE SCHOLAR
  25. 25.Magne, T. M.; de Oliveira Vieira, T.; Alencar, L. M. R.; Junior, F. F. M.; Gemini-Piperni, S.; Carneiro, S. V. et al. Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications. In Journal of Nanostructure in Chemistry. 2022;Vol. 12(Issue 5). https://doi.org/10.1007/s40097-021-00444-3DOIGOOGLE SCHOLAR
  26. 26.Mahalakshmi, D.; Nandhini, J.; Meenaloshini, G.; Karthikeyan, E.; Karthik, K. K.; Sujaritha, J. et al. Graphene nanomaterial-based electrochemical biosensors for salivary biomarker detection: A translational approach to oral cancer diagnostics. Nano TransMed. 2025a;4:Article 100073. https://doi.org/10.1016/J.NTM.2025.100073DOIGOOGLE SCHOLAR
  27. 27.Min, H.; Zhu, S.; Safi, L.; Alkourdi, M.; Nguyen, B. H.; Upadhyay, A. et al. Salivary diagnostics in pediatrics and the status of saliva-based biosensors. In Biosensors. 2023;13(2):Article 206. https://doi.org/10.3390/bios13020206DOIGOOGLE SCHOLAR
  28. 28.Mishra, A.; Singh, P. K.; Chauhan, N.; Roy, S.; Tiwari, A.; Gupta, S. et al. Emergence of integrated biosensing-enabled digital healthcare devices. In Sensors and Diagnostics. Royal Society of Chemistry. 2024;3(5):718–744. https://doi.org/10.1039/d4sd00017jDOIGOOGLE SCHOLAR
  29. 29.Nandhini, J.; Karthikeyan, E.. Crosstalk between cancer-associated fibroblasts (CAF) and tumour cells in head and neck cancer—Unraveling the complex pathway and CAF-targeted therapy. Oral Oncology Reports. 2024;12:Article 100690. https://doi.org/10.1016/J.OOR.2024.100690DOIGOOGLE SCHOLAR
  30. 30.Neumaier, D.; Pindl, S.; Lemme, M. C.. Integrating graphene into semiconductor fabrication lines. In Nature Materials. 2019;18(6):525–529. https://doi.org/10.1038/s41563-019-0359-7DOIGOOGLE SCHOLAR
  31. 31.Pirzada, M.; Altintas, Z.. Nanomaterials for healthcare biosensing applications. In Sensors. 2019;19(23):Article 5311. https://doi.org/10.3390/s19235311DOIGOOGLE SCHOLAR
  32. 32.Ravikumar, L.; Velmurugan, R.. Innovations in early detection of oral cancer: Advancing diagnostic technologies and reducing global disparities. Oral Oncology Reports. 2024;11:Article 100620. https://doi.org/10.1016/J.OOR.2024.100620DOIGOOGLE SCHOLAR
  33. 33.Shpitzer, T.; Hamzany, Y.; Bahar, G.; Feinmesser, R.; Savulescu, D.; Borovoi, I. et al. Salivary analysis of oral cancer biomarkers. British Journal of Cancer. 2009;101(7):1194–1198. https://doi.org/10.1038/sj.bjc.6605290DOIGOOGLE SCHOLAR
  34. 34.Song, J.; Luo, Y.; Hao, Z.; Qu, M.; Huang, C.; Wang, Z. et al. Graphene-based wearable biosensors for point-of-care diagnostics: From surface functionalization to biomarker detection. Materials Today. Bio. 2025;32:Article 101667. https://doi.org/10.1016/J.MTBIO.2025.101667DOIGOOGLE SCHOLAR
  35. 35.Tandale, P.; Choudhary, N.; Singh, J.; Sharma, A.; Shukla, A.; Sriram, P. et al. Fluorescent quantum dots: An insight on synthesis and potential biological application as drug carrier in cancer. Biochemistry and Biophysics Reports. 2021;26:Article 100962. https://doi.org/10.1016/J.BBREP.2021.100962DOIGOOGLE SCHOLAR
  36. 36.Ullah, S.; Shi, Q.; Zhou, J.; Yang, X.; Ta, H. Q.; Hasan, M. et al. Advances and trends in chemically doped graphene. In Advanced Materials Interfaces. 2020;7(24).). https://doi.org/10.1002/admi.202000999DOIGOOGLE SCHOLAR
  37. 37.Ullah, S.; Yang, X.; Ta, H. Q.; Hasan, M.; Bachmatiuk, A.; Tokarska, K. et al. Graphene transfer methods: A review. In Nano Research. 2021;14(11):3756–3772. https://doi.org/10.1007/s12274-021-3345-8DOIGOOGLE SCHOLAR
  38. 38.Verma, D.; Yadav, S. K.; Kalkal, A.; Pradhan, R.; Packirisamy, G.. An ultrasensitive electrochemical immunosensor comprising green synthesized α-Fe2O3NPs_rGO nanocomposite for determination of oral cancer. IEEE Sensors Letters. 2023;7(12):1–4. https://doi.org/10.1109/LSENS.2023.3330915DOIGOOGLE SCHOLAR
  39. 39.Wu, Y.-C.; Ning, L.; Tu, Y.-K.; Huang, C.-P.; Huang, N.-T.; Chen, Y.-F. et al. Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population. Journal of the Formosan Medical Association. 2018;117(9):841–848. https://doi.org/10.1016/j.jfma.2017.10.004DOIGOOGLE SCHOLAR
  40. 40.Yoshizawa, J. M.; Schafer, C. A.; Schafer, J. J.; Farrell, J. J.; Paster, B. J.; Wong, D. T. W.. Salivary biomarkers: Toward future clinical and diagnostic utilities. In Clinical Microbiology Reviews. 2013;26(4):781–791. https://doi.org/10.1128/CMR.00021-13DOIGOOGLE SCHOLAR

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Gupta, J. K., Jaganath, P., Babu, R. H., Reddy, K. T. K., Dantinapalli, V. L. S., Elumalai, S., Yadav, T. C., Rachumallu, V. R., Sankar, P., Srinivasan, J. S., & Ravikumar, L. (2026). Graphene-Based Electrochemical Biosensors for Oral Cancer Detection: Advances, Challenges, and Future Prospects-A Systematic Review. Journal of Young Pharmacists, 18(1), 70–79. https://doi.org/10.5530/jyp.20260170