La Rosa, Giusy Rita MariaGiusy Rita MariaLa RosaDel Giovane, CinziaCinziaDel GiovanePedullà, EugenioEugenioPedullàKowalski, JanJanKowalskiChapple, IainIainChappleMinozzi, SilviaSilviaMinozziAmaliya, AmaliyaAmaliyaAmaliyaPolosa, RiccardoRiccardoPolosa2025-05-092025-05-092025-04-17https://boris-portal.unibe.ch/handle/20.500.12422/210123Background Tobacco use is a global issue, and non-combustible nicotine products (NCNPs) like electronic nicotine delivery systems, nicotine pouches, snus, and nicotine replacement therapies offer potential risk/harm reduction for smokers unable or unwilling to quit. Although NCNPs are less harmful than tobacco smoking, their impact on oral health remains unclear. A systematic review and network meta-analysis will be conducted to answer the research question: What are the oral signs and symptoms associated with NCNPs as both monotherapies and combination therapies compared to each other, placebo, standard care, no drug treatment, and combustible cigarette smoking?Methods We will search PubMed and Scopus databases, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to August 2024. This review will focus on randomized controlled trials (RCTs) with a minimum follow-up period of 1 month, comparing any NCNPs versus placebo, standard care, no drug treatment, combustible cigarette smoking or to each other in adult smokers. Our primary outcomes will be the number of participants reporting any oral side effect, aphthous ulcers, dry mouth and mouth irritation. Studies will be excluded if they involve: non-smokers, pregnant women, individuals with mental health or neurological disorders, participants consuming alcohol or other substances. Data will be analyzed using a network meta-analysis framework, estimating odds ratios with 95% confidence intervals. Risk of bias will be determined using the Cochrane risk of bias tool-version 2.0 for included RCTs and the Confidence In Network Meta-Analysis tool will be employed to assess the confidence of evidence contributing to each network estimate.Discussion Our findings will provide critical insights into the oral health implications of NCNPs, informing clinical and public health decisions. Results are expected by May 2025 and will be disseminated through publications and presentations to guide tobacco harm reduction strategies.Systematic Review Registration PROSPERO CRD42024565118.enElectronic nicotine delivery systemsNetwork meta-analysisNicotine replacement therapyNon-combustible nicotine productsOral healthOral side effect600 - Technology::610 - Medicine & healtharticle10.48620/879154024735910.1186/s13643-025-02839-7