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Objectives: Saccharin test (ST) is a convenient method to assess the efficiency of mucociliary clearance, the primary defense mechanism of the upper airways' tract. The study objectives are to: (1) substantiate its short- (3 days) and long-term (30 days) repeatability; (2) assess its tolerability; (3) conduct a systematic literature review and to compare our results with the existing evidence., Methods: Twenty-nine healthy subjects were enrolled in an observational prospective study to perform an ST on three separate visits (at baseline; at follow-up visits at day 3 and at day 30). Transit times were recorded and self-reported nasal and general symptoms noted. A systematic review of the literature was conducted to compare our results with the existing literature., Results: The mean values (±SD) of ST transit time (STTT) were 7.085 (±2.19), 7.788 (±2.11), and 7.790 (±2.06) minutes at baseline, day 3, and day 30, respectively. Significant linear regression analysis was observed between day 3 and baseline ( r = .193; P = .019) and day 30 and baseline ( r = .182 P = .024). Significant agreement for the intrasession repeatability was observed with an ICC = .354 ( P = .001). Outcomes' comparisons between baseline vs day 3 ( P = .197) and baseline vs day 30 ( P = .173) were not statistically significant. ST was well tolerated. Concordance with existing literature's data and high level of STTT repeatability were confirmed by the qualitative analysis., Conclusion: STTT reproducibility was good both in the short- and long-term. ST tolerability was very good. Our study data are consistent with the existing literature, indicating ST as a sound methodology for detection of early respiratory health changes and for specific regulatory application in respiratory research., Competing Interests: Conflict of interestSalvatore Ferlito and Salvatore Cocuzza are full-time employees of the University of Catania, Italy. Alessandro Gulino, Antonino Maniaci, and Rosalia Emma are fixed-term researcher at University of Catania, Italy. Francesca Benfatto is fixed-term researcher at Centro per la Prevenzione e Cura del Tabagismo, University of Catania. Jerome Lechien is an associate professor of Mons University; Angelo Ingrassia is an ENT specialist from Catania University. Riccardo Polosa was awarded an Investigator-Initiated Study award program established by Philip Morris International in 2017, but subsequently resigned from the role of Principal Investigator in 2018, before the trial began. Lecture fees from a number of European EC industry and trade associations (including Fédération Interprofessionnelle de la VAPE in France and Federazione Italiana Esercenti Svapo Elettronico in Italy) were directly donated to vaper advocacy no-profit organizations. RP is the Founder of the Center of Excellence for the acceleration of Harm Reduction at the University of Catania (CoEHAR), which has received a grant from Foundation for a Smoke Free World to develop and carry out eight research projects. RP is also currently involved in the following pro bono activities: scientific advisor for LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti-Smoking League), and Chair of the European Technical Committee for standardization on Requirements and test methods for emissions of electronic cigarettes (CEN/TC 437; WG4). Pasquale Caponnetto is paid by the University of Catania as an external part-time researcher and adjunct professor of clinical, addiction, and general psychology. He has been affiliated to the CoEHAR since December 2019 in a pro bono role. He is coauthor of a protocol paper supported by an Investigator-Initiated Study award program established by Philip Morris International in 2017. The other authors have no conflict of interests to declare

Objectives: To provide an in-depth analysis of noninvasive methods for the early diagnosis of oral premalignant lesions, focusing on novel biomarkers and optical technologies, and to discuss their potential in improving the prognosis of patients with oral oncological diseases. Methods: This state-of-the-art review examines various noninvasive diagnostic techniques, including the utilization of salivary microRNAs and optical technologies such as Raman spectroscopy, elastic scattering spectroscopy, diffuse reflectance spectroscopy, narrow-band imaging, autofluorescence imaging, toluidine blue staining, and microendoscopy. Results: Several noninvasive techniques have shown varying degrees of effectiveness in detecting oral cancer. Autofluorescence imaging exhibited sensitivities up to 100% but had variable specificity. toluidine blue staining reported sensitivity between 77% and 100% for high-risk lesions or cancer, with specificity around 45% to 67%. Spectroscopy techniques achieved 72% to 100% sensitivities and specificities of 75% to 98%. Microendoscopy presented a sensitivity of 84% to 95% and a specificity of 91% to 95%. Conclusion: The review highlights the strengths and limitations of each noninvasive diagnostic method and their recent advancements. Although promising results have been demonstrated, there is a need for further development of reliable strategies for early detection and intervention in oral oncology., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.