Diagnostic accuracy and smoking-driven modulation of salivary MMP-8, MMP-9, and HIF-1α in stage III grade B/C periodontitis: a cross-sectional study.

Authors

Mehmet Fuat Bozaba, Caner Atalay, Gökhan Kasnak, Hilal Toygar, Nur Balcı

Published in

Clinical oral investigations. Volume 30. Issue 9. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Heavy cigarette smoking is a risk factor for Grade C periodontitis according to the 2018 World Workshop classification. This study evaluated the diagnostic accuracy and smoking-driven modulation of salivary HIF-1α, MMP-8, and MMP-9 across four phenotypically defined cohorts: periodontally healthy non-smokers, Stage III Grade B non-smokers, periodontally healthy heavy smokers, and Stage III Grade C heavy smokers.
Eighty systemically healthy adults (n = 20/group) underwent full-mouth periodontal examination, including probing depth (PD), bleeding on probing (BOP%), clinical attachment level (CAL), plaque index (PI), and radiographic bone loss (RBL). Unstimulated whole saliva was analyzed for HIF-1α, MMP-8, and MMP-9 by ELISA. Statistical analyses included Kruskal-Wallis with Dunn-Bonferroni post-hoc, log-transformed GLM adjusted for age, sex, and BMI, and ROC analysis with 2000-iteration bootstrap 95% CIs. A secondary ROC analysis addressed the smoker subgroup (Grade C(S) vs. Healthy(S), n = 40).
MMP-8 achieved an AUC of 0.855 (95% CI: 0.756-0.934; sensitivity 82.5%, specificity 85.0%) for distinguishing periodontitis from healthy controls and retained robust accuracy in smokers (AUC = 0.831; sensitivity 75.0%, specificity 90.0%), significantly outperforming MMP-9 (AUC = 0.702; ΔAUC = 0.154, p = 0.005). HIF-1α showed no diagnostic value (AUC = 0.453) but was independently suppressed by smoking (β=-0.394, p = 0.007), consistent with chronic PHD2/PHD3-mediated hypoxia adaptation. Notably, BOP% was significantly higher in Grade B (NS) (44.6 ± 25.3%) than in Grade C (S) (30.9 ± 16.5%), consistent with tobacco-induced vascular suppression of gingival bleeding. The BOP% difference between Grade B (NS) and Grade C (S) did not reach statistical significance after Bonferroni correction (p = 0.593), consistent with the known vasoconstriction-mediated suppression of gingival bleeding in heavy smokers.
Salivary MMP-8 demonstrated clinically meaningful diagnostic accuracy (AUC = 0.855) maintained in heavy smokers despite suppressed bleeding (AUC = 0.831). Paradoxical HIF-1α suppression by smoking, independent of periodontal status, positions this marker as a mechanistic indicator of tobacco-driven hypoxia adaptation rather than a periodontitis diagnostic tool.
In Grade C periodontitis patients where tobacco suppresses gingival bleeding, salivary MMP-8 provides adjunctive diagnostic value unaffected by this masking effect (smoker subgroup AUC = 0.831), supporting its use as a point-of-care adjunct where conventional bleeding-based indices underestimate inflammatory burden. The HIF-1α suppression phenotype in healthy smokers represents a novel tobacco-host interaction target warranting further mechanistic investigation.

PMID:
42603195
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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