## 3 Characteristics of the Studies
### Fractal Objects  
The sample source objects for the fractal analyses comprised histological specimens, clinical pictures, radiological images, salivary samples, and cytobrushes. The main application of the FD was to perform textural features for improved classification of oral histopathological images. The most frequent purpose that emerged from the studies was diagnosis to discriminate among normal mucosa, various degrees of dysplasia, OPMDs, and OC. Other research focused on the prognostic significance of nuclear fractal dimensions  
Figure 1: PRISMA flowchart.  
among oral squamous cell carcinoma (OSCC), thus relating to other classical prognostic factors such as lymphatic invasion or tumoral neovascularization. Other works explored multifractal alterations in the oral subepithelial connective tissue during the progression of pre-cancer and cancer or else integrated tumor and stromal features into a single prognostic factor of the oral cancer microenvironment [38]. Some reports further explored the nuclear fractal dimension in oral squamous cell carcinoma to evaluate grading, staging, and survival.  
Fractal analysis was predominantly applied to the analysis of the nuclear fractal dimension [23; 24; 31; 32; 39; 43], in some cases supported by adjunct methods such as fluorescent or immunohistochemical staining [37; 38; 41; 42], while other authors considered the fractal analysis to detect mitotic cells [25]. In some works, the vascular fractal dimension [33] or the geometry of the lymphatic vessels [40] was considered instead.  
Additionally, other works focused on the textural features of the epithelial-connective interface and its regularity or irregularity in healthy specimens compared with oral submous fibrosis (OSF), dysplastic, and cancerous specimens [20; 27; 30; 46], or they studied the OC-associated vasculature [33; 36].  
Furthermore, apart from the classical nuclear fractal dimension, some researchers used immunohistochemical and fractal analysis to focus on specific OC-related cell markers according to their nuclear localization and quantification, such as [PERSON] et al. [38], who investigated osteopontin, or [PERSON] et al. [40], who investigated podoplanin expression.  
Some cumulative methods added to conventional histology were variously considered, from time-resolved autofluorescence to discriminate tumors from healthy tissues in the oral cavity [41] to tissue microarrays to differentiated nuclear/cytoplasmic biomarkers localization [42].  
Apart from histological samples, some research groups considered alternative sources to be analyzed via fractal analysis. [PERSON] et al. [28] conducted multifractal texture analysis of salivary fern patterns for oral pre-cancers and cancer assessment. Alternatively, [PERSON] et al. [21] performed texture analysis of CT images to characterize oral cancers involving the buccal mucosa. Similarly, [PERSON] et al. [29] investigated fractal dimension and radiomorphometric analysis of orthopanoramic radiographs in patients with tobacco- and areca-nut-associated oral mucosal lesions. The Greek group of [PERSON] et al. [34; 35] compared the fractal dimension of actinic cheilitis and healthy lips from clinical pictures of the vermilion borders.  
Apart from actinic cheilitis, among the OPMDs, FD was widely and preponderantly investigated in oral leukoplakia [22; 26; 44; 45; 46; 47] and oral submuc fibrosis (OSF) [20; 27; 28; 30], mainly by the Indian groups, where OSF is endemic [47]. Regarding OLP, different preliminary studies investigated fractal analysis of mucosal microvascular patterns [36] and fractal dimension analysis to differentiate between lichen planus and leukoplakia [45].