Salivary NO2− Levels in Patients with Cancer: Systematic Review and Meta-analysis

In oxidative conditions, nitric oxide acts as a free radical and possible biomarker in the tumor process; however, literature shows conflicting results in this regard. This review aims to evaluate salivary nitrite (NO 2 − ) concentrations in patients with cancer. A systematic review was conducted following the PRISMA 2020 protocol, previously registered in the PROSPERO (CRD42024578042). The methodological quality of the studies was assessed using the Newcastle–Ottawa scale and the AXIS tool. For quantitative synthesis, standardized mean differences (SMD) will be evaluated with a 95% confidence interval (CI) using inverse variance and random effect. The certainty of the evidence was estimated considering Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. The results demonstrated very low certainty of evidence and high variability. Salivary NO 2 − levels have different behaviors in each type of cancer, but in all of them they are statistically significant compared to control values (breast cancer: SMD − 4.52, CI − 5.35 to − 3.69; oral carcinoma: SMD 3.62, CI 2.93–4.31; esophageal cancer: SMD − 0.87, CI − 1.57 to − 0.17). Variables such as sex, localization of tumors, and oral health condition can impact results. NO 2 − levels could be a salivary biomarker with different behaviors for different types of cancer.