Meiosis-Related genes STAG3/SYCP2 as HPV-Linked Biomarkers in Oral and Head-Neck Squamous Carcinoma: Integrative Analyses and Clinical Validation

This study aims to characterize the expression of STAG3 and SYCP2 in head and neck squamous cell carcinoma (HNSCC), assess HPV-stratified co-expression, and clinically validate findings in an oral squamous cell carcinoma (OSCC) cohort.Public resources (UALCAN, TIMER, and HPVTIMER) were queried to compare tumor versus normal expression in HNSCC and to evaluate STAG3-SYCP2 co-expression overall and by HPV status.In cBioPortal, two cohorts were defined: the full HNSCC cohort and an OSCC subset identified by Primary Tumor Site = "Oral Cavity."The top 50 genes were presented, and STAG3/SYCP2 were highlighted.An independent OSCC cohort (HPV⁺ n = 13; HPV⁻ n = 106) underwent RT-qPCR of tumors and paired adjacent tissues.Diagnostic performance for HPV status was assessed by ROC; survival was explored using Kaplan-Meier analyses.Across public datasets, both genes were significantly upregulated in HNSCC, with stronger elevation in HPV⁺ tumors.TIMER and HPVTIMER confirmed robust positive co-expression overall and within HPV⁺ subsets.In the cBioPortal OSCC subset (HPV⁺ n = 12; HPV⁻ n = 160), an HPV⁺dominant up-regulation pattern was observed, with SYCP2 and STAG3 among the top 50 differentially expressed genes.In the clinical OSCC cohort, both genes were higher in tumors than in paired normal tissues and higher in HPV⁺ than HPV⁻ cases, with strong HPV discrimination.No significant overall-survival differences in the full cohort, while HPV⁺ patients exhibited borderline trends.STAG3 and SYCP2 are closely linked to HPV stratification in OSCC and provide strong diagnostic utility for HPV status.