Objectives: To provide an in-depth analysis of noninvasive methods for the early diagnosis of oral premalignant lesions, focusing on novel biomarkers and optical technologies, and to discuss their potential in improving the prognosis of patients with oral oncological diseases. Methods: This state-of-the-art review examines various noninvasive diagnostic techniques, including the utilization of salivary microRNAs and optical technologies such as Raman spectroscopy, elastic scattering spectroscopy, diffuse reflectance spectroscopy, narrow-band imaging, autofluorescence imaging, toluidine blue staining, and microendoscopy. Results: Several noninvasive techniques have shown varying degrees of effectiveness in detecting oral cancer. Autofluorescence imaging exhibited sensitivities up to 100% but had variable specificity. toluidine blue staining reported sensitivity between 77% and 100% for high-risk lesions or cancer, with specificity around 45% to 67%. Spectroscopy techniques achieved 72% to 100% sensitivities and specificities of 75% to 98%. Microendoscopy presented a sensitivity of 84% to 95% and a specificity of 91% to 95%. Conclusion: The review highlights the strengths and limitations of each noninvasive diagnostic method and their recent advancements. Although promising results have been demonstrated, there is a need for further development of reliable strategies for early detection and intervention in oral oncology.

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients.
METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention.
RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects.
CONCLUSIONS: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.

The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality.

This review aimed to comprehensively assess the association between tobacco use and oral health outcomes, specifically the presence of premalignant lesions (PMLs), through a synthesis of multiple assessments conducted in diverse populations. A systematic search of relevant literature was performed, and studies meeting the inclusion criteria were selected using appropriate Medical Subject Headings (MeSH) words and Boolean operators. Data from these studies was pooled and analysed using Review Manager 5.4 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen). The Newcastle-Ottawa scale was used to assess the methodological quality of the studies included. The pooled analysis of the five selected papers revealed a significant correlation between tobacco use and an increased prevalence of PMLs among tobacco users. Tobacco users had an odds ratio of 15.22 (95% CI: 10.01-23.15) as compared to non-user cohorts, significant at p 0.0001. This comprehensive synthesis of assessments underscores the detrimental impact of tobacco use on oral health, particularly in terms of potentially malignant lesions. The findings emphasise the urgency of targeted public health interventions to address tobacco consumption and promote oral health awareness, especially in populations with high tobacco consumption rates. Standardisation of methodologies and representation of diverse populations in future research would strengthen the evidence base and facilitate more effective strategies to improve oral health outcomes globally.

Oral leukoplakia is a predominantly white lesion of the oral mucosa that cannot be classified as any other definable lesion with the risk of progressing into malignancy. Despite the advancements in conventional therapy, the rates of malignant transformation remain notably high, affecting 4.11% of adults, due to the difficulty of accurate diagnosis and indistinct treatment. Photodynamic therapy (PDT), being a minimally invasive surgical intervention, employs a variety of factors, including light, nano-photosensitizers (PSs) and oxygen in the management of precancerous lesions. PDT faces limitations in administering photosensitizers (PSs) because of their low water solubility. However, these challenges could be effectively resolved through the incorporation of PSs in nanostructured drug delivery systems, such as gold nanoparticles, micelles, liposomes, metal nanoparticles, dendrimers and quantum dots. This review will give an overview of the different innovative PS approaches in the management of premalignant lesions, highlighting the most recent advancements. From a clinical perspective, it is expected that nanotechnology will overcome barriers faced by traditional therapeutics and will address critical gaps in clinical cancer care.

Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence.
The search terms (\"Oral leukoplakia\" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0.
We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not.
Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia.

This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its effectiveness.
A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases to identify relevant studies. Meta-analysis was performed using Stata15.0 software. Cochran\'s Q test and I2 statistics were used to evaluate heterogeneity, egger\'s test was used to evaluate publication bias.
The analysis of 17 studies included in this study suggests that PDT may be effective in achieving complete response (CR) [ES = 0.50, 95%CI: (0.33,0.66)], partial response (PR) [ES = 0.42, 95%CI: (0.27,0.56)], no response (NR) [ES = 0.19, 95%CI: (0.11,0.27)]in patients with oral leukoplakia. The recurrence rate was also evaluated [ES = 0.13, 95%CI: (0.08,0.18)]. Subgroup analysis showed that various factors such as light source, wavelength, medium, duration of application, clinical and pathological diagnosis classification influenced efficacy of PDT. The lesion areas of the leukoplakia after treatment were reduced by 1.97cm2 compared with those before treatment.
Our findings show that PDT is a viable treatment for oral leukoplakia. However, the effectiveness of the therapy may depend on several factors, as suggested by our subgroup analyses. (Registration no. CRD42023399848 in Prospero, 26/02/2023).

BACKGROUND: This meta-analysis aimed to assess the rate of malignant transformation (MT) of oral leukoplakia (OL) and to study potential risk factors for the MT of OL into oral squamous cell carcinoma (OSCC).
METHODS: We performed a bibliographic search on nine electronic databases, including PubMed, MEDLINE, and Wanfang Data, for data on the MT rate of OL. Possible risk factors were calculated using Comprehensive Meta-Analysis and Open Meta [Analyst] software.
RESULTS: The pooled proportion of OL MT for the total population described in the 26 selected studies was 7.20% (95% confidence interval: 5.40-9.10%). Nonhomogeneous type lesions, higher grades of dysplasia, the location of the lesion (tongue and multifocal), and female sex had significant effects on the MT of OL.
CONCLUSIONS: OL tended to develop into OSCC (7.2%), and those with significant MT risk factors should be subjected to regular follow-up and observation. However, we require large-scale prospective studies to validate these results, together with unified clinicopathological diagnostic criteria, standardized risk factor recording/assessment methods, and long-term follow-up guidelines.

The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation.
PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen\'s d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method.
A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC.
IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.

The histopathological investigations of oral lesions are a basic approach for diagnosing ongoing cancer or pre-cancer associated pathological attributes in the dissected biopsy. The early detection and management of potentially malignant disorders of the lip and oral cavity that require intervention may reduce malignant transformations, or in case any malignancy is detected during surveillance, the appropriate treatment may improve survival rates. This would guide the clinicians to decide the appropriate treatment modality or lesion to achieve a more favorable prognosis. MCM2 protein is involved in DNA replication providing additional information about the prognosis of neoplasms. Some authors have pointed out that MCM proteins have been inversely correlated with salivary tumour differentiation and therefore could be an indicator of proliferation potential. Therefore, it is essential to find the expression of the MCM2 gene in oral leukoplakia and oral squamous cell carcinoma. Electronic databases like Ebscohost, Livivo, Google Scholar and PubMed were searched. Based on the inclusion and exclusion criteria, 2 reviewers (MS and SN) independently selected the relevant articles. Any disagreement was discussed until a consensus was reached. We used the QUADAS-2 tool to assess the quality of the included studies over four key domains: patient selection, index test, reference standard and flow and timing of participants through the study. 10 out of 57 titles were found to meet the eligibility criteria. Biopsied tissue with immunohistochemical staining or advanced diagnostic studies were included. A total of 901 samples were included in the study and different groups were normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). MCM2 proteins are useful diagnostic markers for distinguishing malignant from benign epithelial dysplasia and for early detection and diagnosis of OSCC as an adjunct to clinicopathological parameters.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12070-022-03296-7.