Enhanced salivary correlation between Streptococcus mutans and herpes simplex virus-1 in oral squamous cell carcinoma: a case-control study

Abstract

Streptococcus mutans modulates local immune responses in the oral mucosa and has been implicated in oral squamous cell carcinoma (OSCC) pathogenesis. Emerging evidence suggests that certain oral bacteria can influence viral infections through immune modulation. This case-control study aimed to determine whether the correlation between S. mutans and herpes simplex virus type 1 (HSV-1) differs between OSCC patients and non-tumor controls, thereby elucidating potential bacterial–viral association in the tumor microenvironment. Unstimulated whole saliva samples were collected from 121 individuals, including 60 non-tumor controls and 61 OSCC patients. Real-time qPCR was used to quantify S. mutans 16S rRNA abundance and HSV-1 glycoprotein D (gD) mRNA levels. Mann–Whitney U tests assessed differences between groups, and Pearson’s correlation analyses evaluated bacterial-viral associations. Analysis of covariance (ANCOVA) adjusted for age and sex. Subgroup analyses examined correlations across clinical and demographic factors. Salivary S. mutans 16S rRNA abundance and HSV-1 gD mRNA levels were significantly higher in OSCC patients than in controls (P = 0.0145 and P = 0.0257, respectively). A moderate correlation was observed between S. mutans and HSV-1 in non-tumor controls (r = 0.3806, P = 0.0027), whereas a substantially stronger correlation was evident in OSCC patients (r = 0.7878, P < 0.0001). Subgroup analyses revealed particularly strong correlations in individuals with alcohol consumption (r = 0.9109, P < 0.0001) and smoking history (r = 0.9062, P < 0.0001). This study demonstrates a significantly stronger association between S. mutans and HSV-1 in OSCC than in non-tumor controls. These findings suggest that salivary bacterial–viral co-enrichment warrants further evaluation as a potential biomarker pair and may inform future microbiome-based strategies for OSCC risk assessment and prevention. Salivary S. mutans and HSV-1 are positively correlated in human subjects. OSCC patients show significantly higher S. mutans and HSV-1 levels than controls. Correlation between S. mutans and HSV-1 is markedly stronger in OSCC. Smoking, alcohol use, periodontitis, and OHI-S may influence this association. These findings support a potential salivary biomarker pair in OSCC.