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Salivary metabolomics in oral potentially malignant disorders and oral cancer patients—a systematic review with meta-analysis

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Abstract

Objectives

The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC).

Materials and methods

A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg’s funnel plot.

Results

A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI − 0.25–0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group.

Conclusion

Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC.

Clinical relevance

While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis.

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Funding

This study is funded by the Dental Postgraduate Research Grant (DPRG), Faculty of Dentistry, Universiti Malaya [UMG003E-2023 & UMG022E-2022].

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia

    Nur Syahirah Binti Mohd Nazar, Anand Ramanathan & Kathreena Kadir

  2. Department of Oral and Maxillofacial Surgery, Medicine and Pathology, Faculty of Dentistry, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia

    Nur Syahirah Binti Mohd Nazar & Faezah Binti Rokhani

  3. Oral Cancer Research & Coordinating Center, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia

    Anand Ramanathan, Wan Maria Nabillah Ghani & Kathreena Kadir

  4. Division of Clinical Dentistry, School of Dentistry, International Medical University, Kuala Lumpur, Malaysia

    Pulikkotil Shaju Jacob

  5. Department of Agrotechnology and Bioscience, Malaysian Nuclear Agency, Bangi, Selangor, Malaysia

    Nurul Elma Binti Sabri

  6. Faculty of Science and Technology, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia

    Mohd Sukri Hassan

  7. Private Practice, Tamilnadu, India

    Lalli Dharmarajan

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  1. Nur Syahirah Binti Mohd Nazar
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Contributions

NSMN, AR, WMN made substantial contribution to conception of the study. NSMN and AR contributed to the study selection. NSMN, WMN and AR collected, extracted and managed data. NSMN, FR, KK, NES and MSH performed data processing, interpretation and assessed study quality and risk of bias. PSJ conducted data analysis and strategy for data synthesis. The manuscript was written by NSMN, AR and WMN, tables were prepared by NSMN, FR and AR, figure 1 was prepared by NSMN, AR and KK and figure 2 and 3 was prepared by PSJ. The GRADE approach was attempted by LD. All authors have read, revised critically, and approved the final manuscript.

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Correspondence to Anand Ramanathan.

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Nazar, N.S.B.M., Ramanathan, A., Ghani, W.M.N. et al. Salivary metabolomics in oral potentially malignant disorders and oral cancer patients—a systematic review with meta-analysis. Clin Oral Invest 28, 98 (2024). https://doi.org/10.1007/s00784-023-05481-6

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