Emerging salivary biomarkers for early detection of oral squamous cell carcinoma

Table 1 Salivary biomarkers for oral cancer detection

Cytokine	Biomarker matrix	Validation methods	Biological sample	Results	P value	Ref.
IL-6	Saliva	ELISA	Control (n = 13), OSCC (n = 13)	Salivary IL-6 levels were significantly higher compared to the control group	< 0.001	Arantes et al[9], 2018
IL-8	Saliva	ELISA	Control (n = 13), OSCC (n = 13)	Salivary IL-8 levels were significantly elevated in OSCC patients compared to the control group	< 0.001	Arantes et al[9], 2018
IL-6	Saliva	ELISA	Control (n = 20), OSCC (n = 19)	Elevated levels of IL-6 were identified in the OSCC group	< 0.05	Bastías et al[32], 2024
IL-8	Saliva	ELISA	Control (n = 20), OSCC (n = 19)	High level of IL-8 was identified in the OSCC group	< 0.05	Bastías et al[32], 2024
IL-6	Saliva serum	ELISA	Control (n = 20), OSCC (n = 30)	Significant difference was encountered between the salivary and serum IL-6 levels in the OSCC group and the control one	< 0.001	Chu et al[30], 2019
IL-8	Saliva serum	ELISA	Control (n = 20), OSCC (n = 30)	Highly significant difference was noted in the IL-8 salivary and serum levels of the OSCC group compared to the control one	< 0.001	Chu et al[30], 2019
IL-6	Saliva	ELISA	Control (n = 30), OSCC (n = 30)	Increased salivary levels of IL-6 were identified in the OSCC group compared to the control one	< 0.001	Elbehi et al[24], 2020
IL-8	Saliva	ELISA	Control (n = 30), OSCC (n = 30)	Highly significant difference was identified in the IL-8 levels compared to the control one	< 0.0001	Elbehi et al[24], 2020
IL-6	Saliva	Bio-Plex multiplex	Control (n = 21), OSCC (n = 20)	IL-6 concentration was higher in the OSCC group compared to the control (T0)	0.005	Lee et al[33], 2011
IL-8	Saliva	Bio-Plex multiplex	Control (n = 21), OSCC (n = 20)	IL-8 concentration was higher in the OSCC group compared to the control one (T0)	0.004	Lee et al[33], 2011
IL-6	Saliva serum	ELISA	Control (n = 52), OSCC (n = 52)	Higher levels of IL-6 before the treatment were associated with the survival rate; higher levels were identified in patients with OSCC compared to the controls	< 0.001	Gau and Wong[31], 2007
IL-8	Saliva serum	ELISA	Control (n = 52), OSCC (n = 52)	IL-8 was identified in higher concentrations in the saliva and serum of patients with OSCC	0.01	Gau and Wong[31], 2007
IL-6	Saliva serum	Luminex assay ELISA	Control (n = 9), OSCC (n = 26)	The IL-6 level was significant higher compared to the age-matched controls	0.0002	Assad et al[34], 2020
IL-8	Saliva	Luminex assay ELISA	Control (n = 9), OSCC (n = 26)	IL-8 had a slightly higher concentration in the OSCC group compared to age-matched controls	0.1087	Assad et al[34], 2020
IL-8	Saliva	ELISA	Control (n = 60), OSCC (n = 60)	The concentration of IL-8 was significantly higher in the OSCC group compared to the control	< 0.0001	Baňasová et al[23], 2015
IL-6	Saliva	ELISA	Control (n = 25), OSCC (n = 25)	Salivary IL-6 is significantly elevated in OSCC compared to the healthy control group	< 0.001	Ajdani et al[16], 2022

The table summarizes the key findings from various studies investigating interleukin-6 and interleukin-8 as diagnostic markers for oral cancer, highlighting their validation methods, sample types, and results. IL: Interleukin; ELISA: Enzyme-linked immunosorbent assay; OSCC: Oral squamous cell carcinoma.

Table 2 Clinical study outcomes in oral cancer detection using salivary biomarkers

Ref.	Sample size	Population demographics	Biomarkers tested	Detection methods	Key findings
Arantes et al[9], 2018	Control (n = 13), OSCC (n = 13)	Mixed gender, age 40-70	IL-6, IL-8	ELISA	Significant elevation in salivary IL-6 and IL-8 levels in OSCC patients compared to controls
Bastías et al[32], 2024	Control (n = 20), OSCC (n = 19)	Mixed gender, age 35-75	IL-6, IL-8	ELISA	Higher IL-6 and IL-8 levels in OSCC group, suggesting diagnostic potential
Chu et al[30], 2019	Control (n = 20), OSCC (n = 30)	Mixed gender, age 45-70	IL-6, IL-8	ELISA	Significant differences in IL-6 and IL-8 levels between OSCC and control groups
Elbehi et al[24], 2020	Control (n = 30), OSCC (n = 30)	Mixed gender, age 40-65	IL-6, IL-8	ELISA	Elevated IL-6 and IL-8 levels in OSCC patients, strong diagnostic indicators
Lee et al[33], 2011	Control (n = 21), OSCC (n = 20)	Mixed gender, age 30-60	IL-6, IL-8	Bio-Plex multiplex	Higher IL-6 and IL-8 concentrations in OSCC patients compared to controls
Gau and Wong[31], 2007	Control (n = 52), OSCC (n = 52)	Mixed gender, age 50-80	IL-6, IL-8	ELISA	Significant correlation between elevated IL-6 and IL-8 levels and OSCC survival rates
Assad et al[34], 2020	Control (n = 9), OSCC (n = 26)	Mixed gender, age 40-70	IL-6, IL-8	Luminex assay ELISA	IL-6 significantly higher in OSCC patients; IL-8 slightly elevated
Baňasová et al[23], 2015	Control (n = 60), OSCC (n = 60)	Mixed gender, age 45-70	IL-8	ELISA	Significantly higher IL-8 concentration in OSCC patients compared to controls
Ajdani et al[16], 2022	Control (n = 25), OSCC (n = 25)	Mixed gender, age 50-75	IL-6	ELISA	Elevated IL-6 levels in OSCC, suggesting its potential as a non-invasive marker

The table provides a detailed summary of these clinical studies, showcasing the significant findings and methodologies employed across different research efforts. By examining the outcomes of these investigations, we can better understand the role of salivary biomarkers in the early detection of oral cancer. Each study offers valuable insights into the diagnostic potential of interleukin-6 and interleukin-8, as well as the demographic variations and detection methods utilized. IL: Interleukin; ELISA: Enzyme-linked immunosorbent assay; OSCC: Oral squamous cell carcinoma.

Table 3 Summary of studies on salivary biomarkers for oral squamous cell carcinoma detection

Biomarker	Sample type	Method	Sample size	Key findings	Ref.
DNA & RNA biomarkers
TP53 mutation	Saliva	qPCR	OSCC (n = 50), controls (n = 50)	Significant mutation detected in OSCC patients	Cristaldi et al[35], 2019
MiRNA-21	Saliva	RT-PCR	OSCC (n = 40), controls (n = 40)	Elevated levels associated with tumor progression	Van Der Hofstadt et al[36], 2024
CDKN2A methylation	Saliva	NGS	OSCC (n = 60), controls (n = 60)	Hypermethylation observed in OSCC samples	Cui et al[37], 2021
Metabolites
Spermidine	Saliva	Mass spectrometry	OSCC (n = 30), controls (n = 30)	Elevated levels in OSCC patients	Er et al[38], 2015
Choline	Saliva	LC-MS	OSCC (n = 50), controls (n = 50)	Altered metabolic profile linked to cancer progression	Zhang et al[39], 2012
Microbiota
Fusobacterium nucleatum	Saliva	16S rRNA sequencing	OSCC (n = 45), controls (n = 45)	Increased abundance in OSCC patients	Kostic et al[40], 2013
Porphyromonas gingivalis	Saliva	qPCR	OSCC (n = 40), controls (n = 40)	Strong correlation with cancer presence	Michaud et al[41], 2017

This table summarizes key clinical studies investigating salivary biomarkers for the detection of oral squamous cell carcinoma, categorized into DNA/RNA biomarkers, metabolites, and microbiota. For each biomarker, the table includes the sample type, detection methods, sample size, key findings, and relevant references. These studies highlight the diagnostic potential of various biomarkers, with an emphasis on their utility for detecting oral squamous cell carcinoma at early stages and contributing to personalized treatment strategies. qPCR: Quantitative polymerase chain reaction; RT-PCR: Reverse transcription polymerase chain reaction; NGS: Next-generation sequencing; LC-MS: Liquid chromatography-mass spectrometry; OSCC: Oral squamous cell carcinoma; 16S rRNA: 16S ribosomal RNA.