Aim: To (i) assess the prevalence, incidence, and burden of severe periodontitis and edentulism in 2021, and (ii) forecast their rates in 2050.Methods: Prevalence, incidence, and Years Lived with Disability (YLDs) for severe periodontitis and edentulism in 2021 were gathered globally, covering 204 countries, seven super regions, and 21 regions from the Global Burden of Disease (GBD) 2021 study. Prevalence, incidence, and YLDs due to periodontitis and edentulism to 2050 were projected using mixed‐effects models with the socio‐demographic index as the main covariate.Results: In 2021, over 1 billion people were affected by severe periodontitis (1066.95 million; 95% UI: 896.55–1234.84), with a global age‐standardized prevalence of 12.50% (10.53–14.49). South Asia had the highest prevalence rate, at 17.57% (14.73; 20.14). Edentulism affected 353 million people globally (300.60–416.20), resulting in an age‐standardized prevalence of 4.11% (3.50; 4.83). The highest edentulism prevalence was found in Latin America and the Caribbean, at 7.39% (6.44; 8.39). By 2050, more than 1.5 billion people (+44.32%) are projected to have severe periodontitis, and over 660 million (+84.40%) to be edentulous. In the same year, 19.67% (130.23 million) of the edentulous people worldwide will be located in China. Severe periodontitis is expected to move up one position, and edentulism nine positions, among the most impactful Level 4 diseases/conditions affecting YLDs worldwide by 2050.Conclusion: Severe periodontitis and edentulism remain major public health challenges in 2021, with the number of affected individuals projected to rise significantly in the coming decades.

Cross‐sectional studies are widely utilized in medical research to estimate prevalence and examine associations. As such, they can serve as a significant source of data for systematic reviews. However, specific considerations are necessary when evaluating the risk of bias (RoB) of cross‐sectional studies, as several potential biases can undermine the validity, reliability, and robustness of their findings. This article introduces a novel, context‐specific tool designed to assess the RoB of cross‐sectional studies for use in systematic reviews. The proposed tool represents an adaptation of the Newcastle‐Ottawa Scale (NOS), originally developed for cohort and case–control studies. Similar to the original NOS, the new tool (named “NOS‐xs”) features a nine‐star rating system to assess six specific items across three main domains: (i) study sample selection, (ii) assessment of exposure(s) and outcome(s), and (iii) confounding factors. Based on the number of awarded stars, studies are categorized as having high (0–3 stars), moderate (4–6 stars), or low (7–9 stars) RoB. The NOS‐xs tool maintains consistency with the original NOS tool, facilitating its integration into systematic reviews that also include cohort and/or case–control studies. While the NOS‐xs is suited to analytical cross‐sectional studies (i.e., association studies), a simplified version (“NOS‐xs2”) is also introduced for descriptive cross‐sectional studies (i.e., prevalence studies). The NOS‐xs2 features a four‐star rating system to assess three of the six specific items included in the NOS‐xs. To streamline their application, spreadsheets for both NOS‐xs and NOS‐x2 are provided.

Periodontitis has been independently associated with the chronic noncommunicable diseases that most frequently lead to death worldwide. The aim of the present systematic review was to study whether people with periodontitis/edentulism are at increased risk of all-cause and cause-specific mortality as compared with those without periodontitis/edentulism. Cohort studies were included that 1) evaluated periodontitis or edentulism as exposures in relation to all-cause or cause-specific mortality as an outcome and 2) reported effect estimates as hazard ratios, risk ratios, or odds ratios with 95% CIs or crude numbers. Two review authors independently searched for eligible studies, screened the titles and abstracts, did full-text analysis, extracted the data from the published reports, and performed the risk-of-bias assessment. In case of disagreement, a third review author was consulted. Study results were summarized through random effects meta-analyses. A total of 57 studies were included, involving 48 cohorts and 5.71 million participants. Periodontitis was associated with increased risk of all-cause mortality (risk ratio, 1.46 [95% CI, 1.15 to 1.85]) and mortality due to cardiovascular diseases (1.47 [1.14 to 1.90]), cancer (1.38 [1.24 to 1.53]), coronary heart disease (2.58 [2.20 to 3.03]), cerebrovascular diseases (3.11 [2.42 to 3.98]), but not pneumonia (0.98 [0.69 to 1.38]). Edentulism (all types) was associated with increased risk of all-cause mortality (1.66 [1.46 to 1.88]) and mortality due to cardiovascular diseases (2.03 [1.50 to 2.74]), cancer (1.55 [1.24 to 1.94]), pneumonia (1.72 [1.07 to 2.78]), coronary heart disease (2.98 [2.43 to 3.65]), and cerebrovascular diseases (3.18 [2.24 to 4.51]). Periodontitis and its ultimate sequela (edentulism) are associated with an increased risk of all-cause and cause-specific mortality (PROSPERO CRD42018100095).

This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low‐grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro‐aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non‐indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor‐associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor‐infiltrating T cells) and the increased expression of pro‐inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors.

As the whole world is epidemically aging, the burden of periodontitis and tooth loss is becoming a major health concern. Growing meta-epidemiological data implicate chronic systemic inflammation/infection due to periodontitis as an independent risk factor for aging-related diseases and mortality. However, because people age differently, chronological age is not a reliable marker of an individual’s functional status. Recent advances in geroscience have shown that various biomarker signatures of biological aging are longitudinally associated with declined physical function, morbidity, and mortality due to major age-related diseases, including periodontitis. Here, we emphasize novel research developments bidirectionally linking periodontitis to accelerated biological aging. Using a composite biomarker age estimator, a striking increase in periodontitis and tooth loss was observed in subjects whose biological age at baseline was higher than their chronological age. Moreover, significantly shortened telomeres were encountered in populations affected by severe periodontitis. Second, we elucidate the cellular and molecular pillars of the aging process at the periodontal level. Accumulating evidence suggests that cellular senescence, stem cell exhaustion, and immunoaging are hallmarks of biological aging implicated in the impairment of periodontal homeostasis and the pathophysiology of periodontitis. Indeed, persistent bacteria-derived lipopolysaccharide stimulation influences cellular senescence in osteocytes, driving alveolar bone resorption. Moreover, inflammaging status induced by chronic hyperglycemia elevates the burden of senescent cells in gingival tissues, impairing their barrier function. Lastly, we reviewed a recent breakthrough in senotherapy to directly target the mechanisms of aging at the periodontal level. Physical exercise and intermittent fasting, together with natural compounds, senolytic drugs, and cell therapy, are increasingly being evaluated to rejuvenate the oral cavity. Following these innovations in geroscience, further advancements could provide oral clinicians the chance to intercept biological aging when still “subclinical” and set interventions for halting or delaying the trajectory toward aging-related diseases while patients are still chronologically young.