The manuscript was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) incorporating network meta-analysis for health care interventions  and the protocol was registered with PROSPERO (CRD42021285397). The focused question analyzed in this systematic review was “Is there a difference in periodontal parameters (bleeding on probing (BoP), plaque index (PI), probing depth (PD)) among tobacco smoking, electronic cigarette smoking and non-smoking healthy patients?” The Population, Exposition, Comparison, Outcome (PECO) scheme was taken into consideration in applying eligibility criteria for the focused question.
Population: Healthy patients with no history of periodontists;
Exposition: Use of electronic cigarettes or tobacco smoking;
Comparison: Non-smoking patients;
Outcomes: Periodontal parameters including PD, PI, and BoP.
Clinical observational and cross-sectional trials investigating periodontal indices among TS, ES, and NS were included. Studies were included only if presented in at least 25 patients in each group and if BoP, PI, and PD values were reported. Traditional cigarette smokers must have been smoking at least 5 cigarettes per day for 1 year. e-cig smokers must have been smoking e-cig exclusively for at least 1 year. Studies with double smokers were excluded. Healthy patients were defined as individuals without systemic diseases (acquired immunodeficiency syndrome, cardiovascular disorders, diabetes, hepatic, and renal disorders). Studies were excluded if patients reported having used antibiotics, non-steroidal anti-inflammatory drugs, and/or steroids within the last 3 months.
Case reports, case series, systematic reviews, animal studies, and in vitro studies and redundant studies were excluded.
A literature search was carried out using electronic databases (MEDLINE (PubMed), ISI Web of Science, and Scopus). A PubMed search was created and adapted to each database: ((electronic cigarettes) OR (vaping) OR (electronic nicotine delivery systems) OR (e-cigarettes)) AND (dental OR gingiva), and the last electronic search was carried out in December 2021. The references of all the included studies and relevant systematic reviews were screened for additional studies and neither language nor date of publication restriction was adopted.
Additionally, a hand search, based on the number available online since 2000, was conducted in the following journals: Journal of Periodontology, Journal of Clinical Periodontology, Clinical Oral Investigations, International Journal of Periodontics, and Restorative Dentistry.
Two authors (P. P., G. U.) examined the titles, abstracts, and full texts of the identified articles to check the respect for the inclusion criteria. Cohen’s Kappa was used to assess the inter-examiners agreement. Disagreements were resolved by discussion or by consulting a third reviewer (GT). Full texts of all the eligible articles were downloaded, and in case of exclusion, the reasons for exclusion were registered.
An Excel data sheet (Microsoft Corp.) was used to extract data. Two authors (G. U., P. P.) extracted the following data: study design, country, sponsor, number of smokers and non-smokers, duration of the smoking habit, sex, age, PD, PI, and BOP. If some information was missing, the authors were contacted to obtain that information.
Risk of bias assessment
Two co-authors (U. G., P. P.) independently assessed the articles according to the NIH quality assessment tool for observational cohort and cross-sectional studies  (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools).
Disagreements were resolved by discussing with another co-author (G. T.). The tool is designed to aid the appraisal of the internal validity of cross-sectional, cohort studies, and case-control studies. It comprises 14 criteria and for each domain, the possible answer is yes, no, or other (CD, cannot determine; NA, not applicable; NR, not reported). All responses other than “yes” indicate a risk of bias. Inherent to the design, cross-sectional studies automatically score “not applicable” on criteria 6, 7, 10, and 13.
After the data extraction process ended, results were pooled together to fit STATA software (network setup command). Relevant assumptions for network meta-analysis were checked, including similarity, transitivity, and consistency . The similarity of included studies was qualitatively assessed, evaluating population, intervention, comparison, and outcome . Transitivity was further assessed by statistically investigating the consistency among the outcomes of direct and indirect comparisons . Hence, network geometry plots and predictive interval plots were created. The network geometry plot was used to illustrate the network of the different groups and analyze connections among them; in this case, we did not disconnect studies nor separate loops. The nodes represent the three groups and edges represent the available direct comparisons between pairs of groups. To estimate the relative ranking of groups using probabilities, surface under the cumulative ranking curves (SUCRA) was used. SUCRA is a simple transformation of the mean rank and is used to provide a hierarchy of the interventions, accounting both for the location and the variance of all relative treatment effects. The larger the SUCRA value, the better the rank of the treatment. A two-tailed P-value of 0.05 was considered significant for hypothesis testing. Information regarding the mean difference, SD, category of subjects, and the number of subjects was extracted from clinical studies. Three separate network meta-analyses were undertaken for PI, PD, and BOP.