Salivary biomarkers in non-invasive oral cancer diagnostics: a comprehensive review.

OBJECTIVE: This review aims to provide a comprehensive analysis of the effectiveness of saliva as a non-invasive diagnostic marker for oral cancer. Despite progress in oral cancer diagnosis and prognosis, the 5-year survival rate remains low due to the resistance to treatment and delayed diagnosis, which can be attributed to various factors including tobacco and alcohol consumption, genetic damage, and human papillomavirus (HPV). The potential use of saliva as an easily accessible non-invasive screening and diagnostic method arises from its direct contact with the lesion site. METHODOLOGY: Data for this study were gathered via a comprehensive literature evaluation using search engines such as the PubMed, Web of Science, Google Scholar, and SciFinder. RESULTS: Identifying salivary biomarkers shows potential to transform oral cancer diagnostics by offering a reliable alternative to the traditional invasive methods. Saliva is an abundant reservoir for both cell-bound and cell-free organic and inorganic constituents. Thus, saliva is an appropriate field for research in proteomics, genomics, metagenomics, and metabolomics. CONCLUSION: This review provides a comprehensive elucidation of salivary biomarkers and their function in non-invasive oral cancer diagnosis, demonstrating their potential to enhance patient outcomes and reduce the impact of this devastating disease.

Analysis of scientific publications on oral cancer diagnosis delays: a bibliometric study over 22 years.

BACKGROUND: The area of oncology still lacks bibliometric studies that investigate the diagnostic interval of oral cancer. This study proposed to carry out a bibliometric analysis of epidemiological studies that investigated the diagnosis of oral cancer between 2002 to 2024. MATERIAL AND METHODS: On April, 2024, the Scopus and Web of Science databases were explored, and the selected articles underwent bibliometric analysis of performance and scientific mapping of journals, authors, institutions, and countries, as well as the predominant topics and trends in research into the diagnosis of oral cancer through an analysis of references and co-occurrence of key words. The analyzes were carried out using the R extension package, Bibliometrix, and the VOSviewer software. RESULTS: A total of 532 documents were included. China contributed the highest number of publications (36.71%) and total citations [1,584]. Seoane J was the most prolific author [16 (h-index: 9)], while Warnakulasuriya S had the highest total link strength [282 (h-index: 7)] in co-citations. Oral Oncology was identified as the most prolific [231 (72.64%)], co-cited and impactful journal (h-index: 13). Explosions of citations were found for keywords such as "early diagnosis", "biomarker", "saliva", "precancer" and "prognosis", making it evident that in the field of oral cancer diagnosis there is room for new studies focusing in reducing the diagnostic interval, with the research hotspots being the terms "biomarkers", "imaging diagnosis" and "gene expression". CONCLUSIONS: This study provides valuable information that can help researchers and institutions align their research activities according to emerging themes, establish collaborations and allocate resources effectively.

Prevalence of HPV16 L1 protein in oral biopsies: A diagnostic study from Ecuador.

This study was designed to investigate the expression of HPV16 L1-protein in biopsies of oral mucosa samples. The expression of HPV16 L1 protein was investigated in biopsies taken from oral mucosa from patients who required pathological diagnosis of oral lesions. Seventy-two samples were incubated with anti-L1 protein monoclonal antibodies and protein detection was revealed with diaminobenzidine. Expression of L1 protein was performed by a pathologist blinded for tissue diagnosis under light microscopy. Most of the lesions of oral mucosa were present in lining mucosa (75 %) and the most frequent lesion were mucocele (n = 17, 23.6 %), epithelial hyperplasia (n = 6, 8.33 %), fibroma (n = 5, 6.9 %) and inflammatory hyperplasia (n = 5, 6.9 %). L1 protein expression was observed only in five (6.9 %) samples (two squamous cell carcinomas, two epithelial hyperplasia, and one gingival hyperplasia). We concluded that L1 expression in oral biopsies presented a low frequency in oral mucosal biopsies samples.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.

Prevalencia de neoplasias malignas en 2042 casos consecutivos / Prevalence of malignant neoplasms in 2,042 consecutive cases

Introducción: las neoplasias malignas en cavidad oral representan de 3-5% de todas las neoplasias, el carcinoma de células escamosas representa 90%, es la neoplasia más frecuente. Objetivo: identificar la frecuencia de neoplasias malignas diagnosticadas histopatológicamente en 2,042 casos consecutivos en la cavidad oral, en un servicio patológico privado, clasificándolas por edad, sexo y localización. Material y métodos: estudio transversal de un muestreo por conveniencia en un periodo que data de enero de 2017 a diciembre de 2018. Resultados: la prevalencia de neoplasias malignas fue de 6.06% (124/2042). Conclusiones: las neoplasias malignas afectan principalmente a personas mayores de 40 años con predilección por el sexo masculino, probablemente porque las mujeres acuden con mayor frecuencia a evaluaciones médicas (AU)

Introduction: malignant neoplasms in oral cavity represent 3 to 5% of all the neoplasms where squamous cell carcinoma is the most frequent with a representation rate of 90%. Objective: identify the frequency of malignant neoplasms diagnosed histopathologically in 2,042 consecutive cases in the oral cavity in a private oral pathology service, classifying them by age, sex and location. Material and methods: cross-sectional study of a sampling for convenience from the periods of January 2017 to December 2018. Results: the prevalence of malignant neoplasms was 6.06% (124/2042). Conclusions: malignant neoplasms mainly affect people over 40; with a predilection for the male sex, probably because women attend medical evaluations more frequently (AU)

CSChighE-cadherinlow immunohistochemistry panel predicts poor prognosis in oral squamous cell carcinoma.

Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.

An oral cancer screening program in Brazil: Analysis of seven years of outcome after its implementation in the suburban cities of São Paulo.

OBJECTIVE: To describe the implementation of an oral cancer screening program at the Barretos Cancer Hospital (BCH) and present the outcome based on data obtained from 2014 to 2020. MATERIALS AND METHODS: The residents of the Regional Health District of Barretos (DRS-V) were personally invited by community health agents or nurses, and among 13,973 people, 15,222 oral examinations were carried out over the years in 18 of its municipalities. Oral examinations were performed at the Mobile Dental Unit and at the Prevention Department of the BCH. Inclusion criteria were being 35 years of age or older, having a personal history of tobacco or alcohol consumption, or having a lesion in the oral cavity found by community health agent or self-reported, regardless of age or risk factors. RESULTS AND CONCLUSION: The main result of our study was the stages of oral cancer among screen detected cases were smaller compared to cases in the hospital registry, in the state and in Brazil. Oral cancer detection rate per 1,000 oral examinations was 10.7.The early stages of oral cancer found by screening in primary care facilities or using mobile units suggest that, when organized, screening may improve the prognosis of oral cancer.

Use of digital strategies in the diagnosis of oral squamous cell carcinoma: a scoping review.

Telediagnosis uses information and communication technologies to support diagnosis, shortening geographical distances. It helps make decisions about various oral lesions. The objective of this scoping review was to map the existing literature on digital strategies to assist in the diagnosis of oral squamous cell carcinoma. this review was structured based on the 5-stage methodology proposed by Arksey and O'Malley, the Joanna Briggs Institute Manual for Evidence Synthesis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The methods were registered on the Open Science Framework. The research question was: What digital strategies have been used to assist in the diagnosis of oral squamous cell carcinoma? The search was conducted on PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect. Inclusion criteria comprised studies on telediagnosis, teleconsultation or teleconsultation mediated by a professional and studies in English, without date restrictions. The search conducted in June 2023 yielded 1,798 articles, from which 16 studies were included. Telediagnosis was reported in nine studies, involving data screening through applications, clinical images from digital cameras, mobile phones or artificial intelligence. Histopathological images were reported in four studies. Both, telediagnosis and teleconsultation, were mentioned in seven studies, utilizing images and information submission services to platforms, WhatsApp or applications. One study presented teleconsultations involving slides and another study introduced teleconsultation mediated by a professional. Digital strategies telediagnosis and teleconsultations enable the histopathological diagnosis of oral cancer through clinical or histopathological images. The higher the observed diagnostic agreement, the better the performance of the strategy.

Mapping Conformational Changes in the Saliva Proteome Potentially Associated with Oral Cancer Aggressiveness.

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.

Avaliação dos principais fatores de risco associados ao desenvolvimento do carcinoma espinocelular: revisão narrativa de literatura / Evaluation of the main risk factors associated with the development of spinocellular carcinoma: narrative literature review

Introdução: A detecção precoce de lesões malignas na cavidade oral é crucial para a prevenção do câncer oral. Cirurgiões-dentistas desempenham um papel vital ao compreender os fatores de risco do carcinoma espinocelular (CEC) a fim de facilitar essa prevenção. No entanto, a identificação do câncer bucal é complexa, sendo a falta de capacitação um obstáculo para diagnósticos oportunos. Objetivo: Este estudo visa apresentar, por meio de uma revisão de literatura, os fatores de risco associados ao desenvolvimento do CEC a estudantes e profissionais da área. Materiais e métodos: Foi realizada uma busca de artigos científicos publicados entre 2015 e 2023 nas bases de dados SciELO, Pubmed e ScienceDirect. As palavras-chave foram escolhidas com base nos Descritores em Ciências da Saúde (DeCS), abrangendo "Neoplasias Bucais" e "Carcinoma Oral de Células Escamosas". Resultados: Foram identificados 502 documentos. Após critérios de exclusão, 26 artigos científicos originais relacionados ao tema foram considerados elegíveis. Conclusão: O papel do cirurgião-dentista é essencial na prevenção e detecção precoce do câncer oral, exigindo total atualização sobre os fatores de risco para um desempenho eficaz.

Introduction: Early detection of malignant lesions in the oral cavity is crucial for the prevention of oral cancer. Surgeons-dentists play a vital role in understanding the risk factors of squamous cell carcinoma (SCC) in order to facilitate this prevention. However, the identification of oral cancer is complex, being the lack of training an obstacle for timely diagnoses. Objective: This study aims to present, through a literature review, the risk factors associated with the development of CEC to students and professionals of the area. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023 in the SciELO, Pubmed and ScienceDirect databases. The keywords were chosen based on the Describers in Health Sciences (DeCS), encompassing "Buccal Neoplasms" and "Oral Squamous Cell Carcinoma". Results: Foram identified 502 documents. After exclusion criteria, 26 original scientific articles related to the topic were considered eligible. Conclusion: The role of dental surgery is essential in the prevention and early detection of oral cancer, requiring full updating on risk factors for effective performance.

Could Teledentistry Be a Solution in the Diagnosis of Oral Lesions?

In recent years, teledentistry has gained visibility, especially because of the COVID-19 pandemic. Concerning oral medicine, there is great expectation, particularly about its potential to promote early diagnosis of oral lesions. In southern Brazil, two initiatives have shown a positive influence on each other and have led to greater awareness of oral cancer and more access to qualified advice on diagnosing and managing oral lesions. Although the contributions of this approach are promising, there are barriers to be overcome.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Oral cancer screening outcomes in the Latin American region with special relevance to Brazil and Cuba: a systematic review.

BACKGROUND:  The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS:  An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS:  Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS:  Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.

Hamartomas, choristomas, and teratomas of the oral cavity: A 49-years cross-sectional study in an oral diagnostic service.

BACKGROUND: To investigate the incidence and demographic profile of hamartomatous, choristomatous, and teratoid lesions in a Brazilian population over a 49 years-period. METHODS: A retrospective cross-sectional study was performed, and data regarding demographic and clinical aspects were obtained from the medical records of a Brazilian referral center (1970-2019). The collected data were submitted to descriptive analysis and Pearson's chi-square, Fisher's exact, and Kruskal-Wallis tests (p ≤ 0.05). RESULTS: In a total of 16,412 medical records analyzed, 300 (1.83 %) were hamartomatous, 2 (0.01 %) choristomatous, and 1 (0.01 %) teratoid lesions. Hamartomas were most diagnosed in females and adults. Statistical significance was observed between hamartoma and age group (p < 0.001). Odontoma was the most frequent hamartomatous lesion. In choristomatous and teratoid lesions, there was no occurrence in males. The jaws were the most affected anatomical site by hamartoma. Choristomas were observed on the mandible and tongue, while a teratoid lesion was seen on the floor of the mouth. CONCLUSIONS: Low occurrence of choristomatous and teratoid lesions over hamartomatous lesions and a heterogeneous occurrence profile regarding sex, age group, and anatomic site were observed. Hamartomas are relatively common and benign conditions that may cause damage and require special care during dental treatment. Thus, the dentist needs to be able to identify and treat them appropriately. Likewise, although choristomas and teratomas present no risk to patients and have a lower occurrence than hamartomas, they also require treatment.

Cancer in buccal mucosa in patients with Fanconi anemia: Report of six cases.

INTRODUCTION: Fanconi anemia (FA) is a recessive hereditary disease characterized by bone marrow failure, and the treatment is hematopoietic stem cell transplantation (HSCT). Patients diagnosed with FA are more predisposed to develop oral squamous cell carcinoma (SCC), and this risk increases in transplant patients. The clinical characteristics of the oral manifestations of SCC in this group of patients do not differ from the lesions present in patients without the disease; however, they can be diagnosed in young patients and less common locations, such as, for example, in the buccal mucosa. OBJECTIVE: To report a case series of patients diagnosed with FA with oral SCC. METHOD: Included in this case series are six patients diagnosed with SCC in the buccal mucosa with similar clinical characteristics. FINAL CONSIDERATIONS: There are still difficulties in establishing the natural history of oral lesions in patients with FA. Thus, disclosing a series of cases with similar changes may be relevant to improving and refining the multidisciplinary team's clinical view of suspected SCC or oral potentially malignant disorders (OPMD), providing surveillance and timely management.

Accuracy of Remote Examination for Detecting Potentially Malignant Oral Lesions: A Systematic Review and Meta-Analysis.

Objective: We aimed to investigate the accuracy of remote examination by photographs compared to in-person clinical examination for detecting potentially malignant oral lesions (PMOLs). Methods: The Reporting Guide and Guidelines for Writing Systematic Reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA]) guided the reporting of findings. The search was conducted by two independent reviewers in six databases with no language restriction until November 2022. The Population, Test-Index, Reference Standard, Outcome and Study Design (PIROS) strategy guided the eligibility criteria, and studies with adult patients (P) examined remotely (I) and in-person (R) to verify the detection of PMOLs (O) were considered. The methodological quality was assessed by QUADAS-2, and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: A total of 769 files were identified. After removing duplicates and reading titles and abstracts, 16 were read in full, from which 6 articles then comprised the qualitative synthesis. The oral clinical examination was the reference standard in four studies. Five studies presented high risk of bias in at least one assessment domain. A high probability of detection of PMOL by remote examination (97.37%) was observed for the three studies included in the meta-analysis, which presented high heterogeneity among them. The certainty of evidence for the outcome was considered very low. Conclusions: Remote tools for detecting PMOLs may be feasible and assertive, but new studies are required to incorporate them into clinical practice. Clinical Relevance: Remote examination for the detection of PMOLs has the potential to favoring the early diagnosis of malignant lesions.