Genetic variants of EBI3, tumor Epstein-Barr virus, and human cytomegalovirus status in HPV-negative oral cancer.
This study evaluated the clinical relevance of EBI3 polymorphisms, along with tumor Epstein-Barr virus (EBV) and Human Cytomegalovirus (HCMV) status, in prognostically adverse HPV-negative OSCCs.
EBI3 (rs4740, rs4905, rs428253) genotyping was performed by qPCR in 95 HPV-negative OSCC patients and 108 age- and sex-matched controls. Tumor HPV, EBV, and HCMV status were assessed by qPCR. EBV viral load was calculated by exponential approach and a relative estimate of EBV copies per 105 cells. Associations with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier and Cox regression analyses.
EBV-positive tumors showed a significant association with increasing nodal stage (P=0.020). EBV viral load stratification (negative, low, high) presented a non-significant trend toward association with advanced tumor stage (P=0.060). Notably, EBI3 rs428253 predicted worse OS in EBV-positive patients, whereas rs4740 and rs4905 variants were associated with advanced tumor stage (P=0.024 and P=0.018). rs4740 and rs4905 variants were inversely associated with OSCC risk in dominant and overdominant models. Analysis detected HCMV in 7.4% of tumors but was not clinically relevant.
EBI3 genetic variants and EBV status may have prognostic relevance in HPV-negative OSCC. EBV may interact with the host genetics to influence nodal metastases and outcomes, suggesting a potential EBV-EBI3 axis, which warrants further investigation. Future precision oncology approaches may incorporate host and viral genetic markers to identify and stratify high-risk HPV-negative OSCC patients.
EBI3 (rs4740, rs4905, rs428253) genotyping was performed by qPCR in 95 HPV-negative OSCC patients and 108 age- and sex-matched controls. Tumor HPV, EBV, and HCMV status were assessed by qPCR. EBV viral load was calculated by exponential approach and a relative estimate of EBV copies per 105 cells. Associations with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier and Cox regression analyses.
EBV-positive tumors showed a significant association with increasing nodal stage (P=0.020). EBV viral load stratification (negative, low, high) presented a non-significant trend toward association with advanced tumor stage (P=0.060). Notably, EBI3 rs428253 predicted worse OS in EBV-positive patients, whereas rs4740 and rs4905 variants were associated with advanced tumor stage (P=0.024 and P=0.018). rs4740 and rs4905 variants were inversely associated with OSCC risk in dominant and overdominant models. Analysis detected HCMV in 7.4% of tumors but was not clinically relevant.
EBI3 genetic variants and EBV status may have prognostic relevance in HPV-negative OSCC. EBV may interact with the host genetics to influence nodal metastases and outcomes, suggesting a potential EBV-EBI3 axis, which warrants further investigation. Future precision oncology approaches may incorporate host and viral genetic markers to identify and stratify high-risk HPV-negative OSCC patients.
Authors
Simonovic Simonovic, Kozomara Kozomara, Jovic Jovic, Velikic Velikic, Ristanovic Ristanovic, Djordjevski Djordjevski, Djuric-Petkovic Djuric-Petkovic, Stosic Stosic, Supic Supic
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