Search processing

The current systematic review followed the PRISMA and International Prospective Register of Systematic Review Registry procedures (ID: CRD420250616785).

The following databases: PubMed, Web of Science, and Scopus, were examined from 1 October 2014 to 21 November 2024, to search articles of the last 10 years. The search strategy was created by combining terms relevant to the study’s purpose. The following Boolean keywords were applied: (Vaping) OR (Cigarette) OR (Smoking) OR (e-cigarette) OR (Electronic cigarettes) AND (Periodontitis).

Inclusion and exclusion criteria

The reviewers worked in groups to assess all relevant studies that analyzed or compared the impact of smoking traditional cigarettes, E-Cs, and HTPs on periodontal health, with a focus on inflammatory markers and oral tissue response, according to the following inclusion criteria:

• Studies that did the research “in vivo” or in “humans”;

• Case-control studies, cohort studies, RCTs;

• Studies that were published in the last 10 years;

• Studies that fulfill any of the following exclusion criteria were excluded: reviews, case reports and series, letters to the authors, animal models, in vitro studies, and surveys.

Population, intervention, comparison, outcome, study design (PICOS) question

The PICOS question addressed in this systematic review is summarized in Table 1.

Four independent reviewers (B.F.P.P., V.C., D.C., R.V.G.) assessed the quality of the included studies using specified criteria, such as selection criteria, methods of outcome evaluation, and data analysis.

This enhanced ‘risk of bias’ tool additionally includes quality standards for selection, performance, detection, reporting, and other biases. Any differences were settled through conversation or collaboration with other researchers (G. D., A.D.I., V.C., R.V.G., B.F.P.P., D.C., F.I., A.P., A.M.I.). The reviewers (B.F.P.P., V.C., D.C., R.V.G.) screened the records according to the inclusion and exclusion criteria.

Doubts have been resolved by consulting the senior reviewer (F.I.). The selected articles were downloaded into Zotero 8.0.2, a reference management software used to organize and manage bibliographic data.

Characteristics of included articles

Figure 1 shows the flow diagram of a systematic review carried out using the PRISMA reporting criteria. The diagram describes the search strategy, inclusion, and exclusion of publications at each stage of detection. A total of 2,277 publications were identified in three databases, including PubMed (1,957), Web of Science (320), and Scopus (0), obtaining 1,022 records after the duplicates (30) and records marked as ineligible by automation tools, e.g., software such as Excel used to identify duplicates or clearly irrelevant records, and 1,225 articles were deleted. The title and abstract analysis resulted in the exclusion of 796 articles because they were off topic. The remaining 226 records were read, deleting 214 articles that did not fulfil the inclusion criteria. This resulted in a total of 12 publications for qualitative analysis (Table 2).

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Figure 1. Literature search Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram and database search indicators. Adapted from [54]. © Author(s) 2021. Distributed under a Creative Commons CC BY 4.0 license.

Study of the variables

Quality assessment and risk of bias of included articles

The risk of bias in the included studies is reported in Table 3.

Table 3. Bias assessment by the Robins tool.

Authors (year)	D1	D2	D3	D4	D5	D6	D7	Overall
Xu et al. (2021) [55]
Shah et al. (2023) [56]
Kumar et al. (2023) [57]
Holliday et al. (2019) [58]
Karaaslan et al. (2020) [59]
Kiiun et al. (2023) [60]
Akram et al. (2021) [61]
ArRejaie et al. (2019) [62]
ALHarthi et al. (2019) [63]
Mišković et al. (2024) [64]
Pouly et al. (2021) [65]
Al-Hamoudi et al. (2020) [66]

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High: ; low: ; some concerns: ; no information: ; D1: bias due to confounding; D2: bias arising from the measurement of the exposure; D3: bias in the selection of participants into the study (or into the analysis); D4: bias due to post-exposure interventions; D5: bias due to missing data; D6: bias arising from the measurement of the outcome; D7: bias in the selection of the report result.

Regarding bias due to confounding, most studies have a medium risk. The bias resulting from measurement is a parameter with a low risk of bias. Many studies have a low risk of bias due to participant selection. Post-exposure bias is low in most studies. Bias due to missing data is medium in many studies. The bias resulting from the outcome measurement cannot be calculated due to heterogeneity. The selection bias of the reported results is low in 7 of the studies and medium in the other 5.

Although the overall methodological quality of the included studies was acceptable, a moderate risk of bias was identified in several domains, particularly those related to confounding factors and missing data. These limitations should be considered when interpreting the reported associations between E-C or heated tobacco use and periodontal outcomes, as residual confounding cannot be completely excluded.

E-Cs and their effects on non-surgical periodontal therapy (N-SPT)

Different studies have come out to investigate the effect of E-Cs on the outcomes of N-SPT by determining differences in responses among traditional smokers, users of E-Cs, and non-smokers (N-S). Shah et al. (2023) [56] did an investigation of these differences and found that users of E-Cs responded differently compared to traditional smokers; the users of E-Cs showed generally retarded or less marked improvement of periodontal parameters [67–69].

Kumar et al. (2023) [57] further established that E-C users responded less favorably to scaling and root planing (SRP) than N-S, and the issues were more serious in traditional smokers [70, 71].

Al-Hamoudi et al. (2020) [66] further established that E-C users had lower anti-inflammatory cytokine levels following SRP, which could compromise the effectiveness of N-SPT by delaying the resolution of inflammation and healing [72, 73].

Oral microbiome in E-C and heated tobacco users

Both E-Cs and HTPs highly impact the oral microbiome, generally by enriching pathogenic species that may well contribute to periodontal disease exacerbation. Mišković et al. (2024) [64] presented a study about subgingival biofilm in both E-C and heated tobacco system users [74, 75]. An increased appearance of periodontopathogenic bacteria was found in these groups compared to the group of N-S. This modified composition may partly account for their higher predisposition to periodontal diseases compared with users of other methods of smoking. The enriched pathogenic species may promote tissue destruction and inflammation; thus, management of periodontitis may be more distressing as compared to traditional smokers and N-S [76–78].

Inflammation and immune modulation in E-C users

E-C exposure has been associated with increased inflammatory oral responses that may negatively affect periodontal status by immune modulation.

ArRejaie et al. (2019) [62] proved that the peri-implant tissues of E-C users showed similar levels of inflammation to traditional smokers, with significantly higher levels of pro-inflammatory cytokines compared to N-S [79, 80]. This is further supported by Al-Hamoudi et al. (2020) [66], who showed that following periodontal treatment, E-C users had impaired anti-inflammatory responses, which may extend the period of inflammation. Thus, high levels of inflammatory markers among E-C users suggest chronic inflammation that can lead to the complication of periodontal management due to impaired healing and poor treatment outcomes [81, 82].

Effects of E-Cs and heated tobacco on the course of periodontitis

A number of longitudinal studies have evaluated the effects of E-Cs and HTPs on the progression of periodontitis. Holliday et al. (2019) [58] discussed the effects of E-Cs on smoking cessation and periodontal health in subjects [83]. It was noted that, upon cessation of smoking, periodontal health improves, but residual effects of previous smoking continue, most highly among users of E-Cs. Mišković et al. (2024) [64] noted that the periodontal health among users of E-Cs and heated tobacco showed considerably poorer health than in non-smoking subjects, though heated tobacco users showed slightly better evidence than traditional smokers [84]. Pouly et al. (2021) [65], on their part, carried out multicenter studies confirming that the periodontal improvements after switching from cigarettes to heated tobacco remained inferior to those achieved through complete cessation [61, 85, 86]. Interpretation of disease progression in E-C and heated tobacco users should be approached with caution, as the available evidence is largely derived from observational or cross-sectional studies and is characterized by limited follow-up durations. The lack of long-term data, together with substantial variability in exposure patterns, frequency, and duration of use across studies, introduces uncertainty regarding the cumulative and sustained effects of these products on periodontal tissues.

Tissue and clinical biomarkers in periodontitis

Progression among smokers and E-C users: Tissue degradation and clinical biomarkers give some insight into the process of periodontitis among smokers and E-C users. Akram et al. (2021) [61] proved that the pattern of degradation in tissues was similar to that of traditional smokers, hence establishing that both user groups are at higher risks of periodontal damage than N-S [56, 87]. According to ALHarthi et al. (2019) [63], the chronic states of periodontitis in both traditional smokers and E-C users were indeed complex to handle, as higher levels of ultrasonic scaling were needed in these groups to reduce inflammation, though the rate of healing was also slower compared to the N-S group. These findings indicate that E-C use enhances periodontitis, similar to conventional smoking, and compromises the treatment process.

Oral dysbiosis and enzymatic activities related to E-C use

Kiiun et al. (2023) [60] studied oral dysbiosis and enzymatic activity in relation to periodontal disease insubjects using E-C. In the present study, big changes in oral microbiota were found, including increased urease and lysozyme activity, in E-C smokers in accordance with a significant increase in pathogenic bacteria [88]. Thus, this microbial imbalance, together with enzymatic changes, could point out that the environment for periodontal tissues due to E-C use is even more dangerous, leading to an even higher risk of disease progression. This oral dysbiosis, therefore, adds another level of complication in the periodontal care and treatment outcome of such patients [89–91].

Tobacco cessation and E-Cs: effects on periodontal health

The use of E-Cs as an aid to smoking cessation regarding the long-term implications for periodontal health has been argued. Accordingly, though E-Cs may help in smoking cessation, the use of E-Cs does not considerably offer a long-term periodontal health benefit compared to complete smoking cessation [92–94]. There is some improvement in periodontal status among E-C users, which was not that strong compared to their N-S counterparts [95–97]. In contrast, Pouly’s 2021 study [65] reported modest gains in periodontal health among subjects who switched from cigarettes to heated tobacco; even these gains did not compare to the subjects who attained complete smoking cessation.

Ultrasonic scaling and periodontal treatment among E-C users and traditional smokers

Full-mouth ultrasonic scaling is one of the common N-SPT. It has been noted to be variably effective in smokers and E-C users. For example, ALHarthi et al. (2019) [63] compared the healing of patients with gingival inflammation who either use or do not use E-Cs and established that the E-C users recover more slowly after scaling, just like traditional smokers. This was further supported by Al-Hamoudi et al. (2020) [66], who concluded that E-C users continuously maintained the inflammatory markers even after scaling and root planning, hence indicating a status that may affect the overall healing process and treatment success.

Impact of heated tobacco and E-Cs on subgingival flora

Mišković et al. (2024) [64] conducted a profound analysis of subgingival biofilm in users of E-C and heated tobacco systems. It was noted that in the biofilm of both groups, there was a much higher amount of pathogenic species than among traditional smokers and N-S [98, 99]. Therefore, the microbial environment that developed in both E-C and heated tobacco users is more likely to support periodontal disease development due to increased abundance of pathogens, further increasing tissue inflammation and leading to its destruction [100–102]. Results represent the microbiological aspect of the use of alternative tobacco products concerning periodontitis.

Periodontal health in patients exposed to E-C and heated tobacco aerosols

Several cross-sectional studies have assessed the periodontal status of individuals exposed to E-C and heated tobacco aerosols; these studies have presented marked differences in the various clinical parameters assessed [103, 104]. Mišković et al. (2024) [64] showed that both groups had higher pocket depth and attachment loss when compared with N-S. Karaaslan et al. (2020) [59] further illustrated that E-C users had higher peri-implant complications, while ArRejaie et al. (2019) [62] further confirmed that both smokers and E-C users showed heightened peri-implant inflammation. All these studies indicate that, in general, E-Cs and heated tobacco systems have an adverse impact on periodontal and peri-implant health, further complicating the management of periodontal diseases [105, 106].

The findings of this systematic review confirm and extend existing literature regarding the negative impact of E-Cs and HTPs on periodontal health.

In accordance with prior observational and clinical studies, the review highlights that both E-C and HTP use are associated with worsened clinical outcomes following N-SPT, showing patterns of inflammation, delayed healing, and persistent dysbiosis that are comparable to traditional cigarette smoking. Several studies reviewed also align with broader evidence indicating that E-C use may enrich periodontopathogenic bacteria and elevate inflammatory biomarkers, suggesting that the supposed “reduced harm” profile of these alternative products is not reflected in periodontal outcomes. These findings corroborate previous meta-analyses and clinical observations that suggest E-Cs and HTPs do not confer significant periodontal health benefits compared to complete smoking cessation.

An additional limitation of the current evidence lies in the considerable heterogeneity among included studies in terms of study design, population characteristics, clinical endpoints, and periodontal outcome measures. This heterogeneity precluded quantitative synthesis and meta-analysis and limits the comparability of results across studies, thereby restricting the strength of causal inferences that can be drawn from the existing literature.

Despite the growing body of evidence addressing the periodontal effects of E-Cs and HTPs, the current literature remains limited by the absence of large-scale, randomized controlled trials directly comparing these products with conventional cigarette smoking within standardized periodontal treatment protocols. Moreover, former smoking status is often insufficiently characterized, particularly with regard to time since cessation or switching, and the potential confounding impact of dual use of electronic or HTPs alongside conventional cigarettes is inconsistently reported. These limitations underscore the need for well-designed longitudinal and interventional studies to clarify the true clinical relevance of alternative tobacco products in periodontal disease progression and management.