Salivary Lactate Dehydrogenase as a Potential Biomarker in Oral Potentially Malignant Disorders and Head & Neck Cancer- A Systematic Review and Meta-analysis.

Background: The prognosis of head &neck cancer (HNC) depends on its early detection, diagnosis, and treatment, which has advocated a search for a simple, reliable, noninvasive, cost-effective tool to aid in the same. Salivary lactate dehydrogenase has gained interest in recent years, meeting the above requisite.

Objectives: To evaluate the levels of salivary lactate dehydrogenase in patients with oral potentially malignant disorders (OPMD), HNC, and in the healthy control group (CG); to find the correlation, grade-wise and genderwise difference between them; and to assess whether it can be used as a potent biomarker in OPMD and HNC.

Materials and methods: A comprehensive search of the specialized 14 databases and 4 institutional repositories was performed for including the studies evaluating salivary lactate dehydrogenase in OPMD and HNC patients either comparing or not comparing to the healthy control group in the systematic review process. The meta-analysis was performed with the eligible study data with the STATA version 16, 2019 software with 95% CI and p ≤ 0.05 in the random-effects model.

Results: Twenty-eight studies of case-control, interventional, or uncontrolled non-randomized design evaluating salivary lactate dehydrogenase were included. A total of 2074 subjects were included, involving HNC, OPMD, and CG. The salivary lactate dehydrogenase levels were significantly higher in HNC than in CG & oral leukoplakia (OL) (p=0.00); in OL & oral submucous fibrosis (OSMF) than CG (p=0.00); and higher in HNC than OSMF, however not significant (p=0.49). Also, the salivary lactate dehydrogenase levels had no significant difference between males and females in CG, HNC, OL, and OSMF groups(p> 0.05).

Discussion: It is evident that the epithelial transformations in the various OPMD and HNC, and the proceeding necrosis in the case of HNC, raises the LDH levels. It's also worth noting that when degenerative alterations continue, the SaLDH levels rise correspondingly, which are higher in HNC than in OPMD. Hence, it is essential to determine the cut-off values for SaLDH for establishing that the patient may have HNC or OPMD. It would be easy to follow-up frequently and perform investigations such as biopsy for the cases with high SaLDH levels, thereby aiding in the early detection and improving the prognosis of HNC. Moreover, the increased SaLDH levels were indicative of a lower degree of differentiation and an advanced disease leading to a poor prognosis. Salivary sample collection is less invasive, simple, and more acceptable to the patient; however, saliva collection is a time-consuming procedure as it is mostly collected by the passive spit method. Also, it is more feasible to repeat the SaLDH analysis during the follow-up, but the method has recently gained interest for over a decade.

Conclusion: Salivary lactate dehydrogenase can be a potential biomarker for the screening, early detection, and follow-up of OPMD or HNC being simple, noninvasive, cost-effective, and readily acceptable modality. However, more studies with new standardized protocols are recommended to determine the precise cut-off levels for HNC and OPMD. Keywords (MeSH): L-Lactate dehydrogenase; Saliva; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Oral; Precancerous conditions.