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.

Reported physical examination methods for screening of oral cancer and oral potentially malignant disorders: a systematic review.

OBJECTIVE: This systematic review aimed to describe the method followed during physical examination and the anatomical structures of the head and neck assessed in screening for oral cancer and oral potentially malignant disorders (OPMDs). STUDY DESIGN: An extensive literature search was carried out using MEDLINE/PubMed, EMBASE, Scopus, LILACS, Web of Science, Cochrane databases, and gray literature. The risk of bias was available in all papers included. RESULTS: Of 9,688 records identified, 27 were included in this review, reporting data from 356,250 individuals screened and distributed across 11 countries. Most of these (n = 19) were based on 1 round of screening conducted by a dental professional or other health care workers. Most screening programs included visual inspection and palpation of the lips, oral cavity, and the most visible oropharyngeal sites, but the descriptions reported were imprecise. Additional inspection and palpation of the neck (submental, submandibular, cervical, and supraclavicular regions) to assess for the presence of swellings and any palpable neck nodes were also performed in 15 programs. CONCLUSION: In conclusion, there was considerable heterogeneity in the method of physical examination in screening programs for oral cancer and OPMDs among the included studies.

Clinical and Psychosocial Impact of Communication about Oral Potentially Malignant Disorders: A Scoping Review.

Delivering bad news has been widely studied in cancer, thus, this scoping review aims to identify the available evidence concerning the communication of oral potentially malignant disorders (OPMDs) and their clinical and psychosocial impacts. A search was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Differences regarding the study design, population, OPMDs assessed, and outcomes of professional-patient communication were found in each study. Protocols for OPMD communication have not yet been reported and there is a need to standardize strategies as communication skills may provide better clinical outcomes for patients diagnosed with potentially malignant disorders. Although future studies are needed, a brief list recommending the aspects that must be communicated is proposed.

Pan-American prevalence of smokeless tobacco use and association with oral potentially malignant disorders and head and neck cancer: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence of smokeless tobacco (SLT) use and its association with oral potentially malignant disorders (OPMDs) and head and neck cancer (HNC) in the Pan-American Health Organization (PAHO) region. STUDY DESIGN: A literature search was conducted across 9 databases and other sources. The eligibility criteria were pediatric (0-18 years old) and adult (19 years and older) populations consuming any type of SLT. Meta-analysis was performed to determine the prevalence of SLT and the association between its use and OPMDs/HNC in the PAHO region; the Grading of Recommendations Assessment, Development, and Evaluation tool was used to verify the certainty of evidence. RESULTS: Fifty-nine studies from 6 PAHO countries were included, of which 51 were also subjected to quantitative analysis. The pooled SLT prevalence of use was 15% (95%CI: 11.93-18.69) overall, 17% (95%CI: 13.25-22.65) in adults, and 11% (95%CI: 8.54-14.78) in the pediatric population. The highest reported SLT prevalence of use was 33.4% (95%CI: 27.17-39.93) in Venezuela. HNC was positively associated with SLT use (OR = 1.98, 95%CI: 1.54-2.55), with a moderate certainty of evidence. Among OPMDs, only leukoplakia reported a positive association with SLT use (OR = 8.38; 95%CI: 1.05-67.25). However, the quality of the evidence was very low. CONCLUSION: A high consumption of SLT use, chewing tobacco and snuff, is reported among the adult population residing in the PAHO region with a positive association with the development of oral leukoplakia and HNC.

Machine learning for detection and classification of oral potentially malignant disorders: A conceptual review.

Oral potentially malignant disorders represent precursor lesions that may undergo malignant transformation to oral cancer. There are many known risk factors associated with the development of oral potentially malignant disorders, and contribute to the risk of malignant transformation. Although many advances have been reported to understand the biological behavior of oral potentially malignant disorders, their clinical features that indicate the characteristics of malignant transformation are not well established. Early diagnosis of malignancy is the most important factor to improve patients' prognosis. The integration of machine learning into routine diagnosis has recently emerged as an adjunct to aid clinical examination. Increased performances of artificial intelligence AI-assisted medical devices are claimed to exceed the human capability in the clinical detection of early cancer. Therefore, the aim of this narrative review is to introduce artificial intelligence terminology, concepts, and models currently used in oncology to familiarize oral medicine scientists with the language skills, best research practices, and knowledge for developing machine learning models applied to the clinical detection of oral potentially malignant disorders.

Oral epithelial dysplasia grading: Comparing the binary system to the traditional 3-tier system, an actuarial study with malignant transformation as outcome.

BACKGROUND: Establishing the risk of malignant transformation (MT) in oral leukoplakia is usually based on grading oral epithelial dysplasia (OED) on biopsy tissue, for which two systems are proposed: a 3-tier and a binary system. Only very few actuarial studies have tested the accuracy of such methods in predicting MT, especially for the binary system. This study aimed to assess the accuracy of the two grading systems in predicting MT in a cohort of oral leukoplakia (OL) from Brazil, with follow-up data. METHODS: The sample comprised 878 individuals diagnosed with OL from 2005 to 2018. Follow-up data were obtained both locally and from the regional cancer registry. All lesions were graded using both the 3-tier and the binary systems. Kaplan-Meier curves (Log-rank Mantel-Cox) were used to assess risk and kappa to assess interobserver agreement. RESULTS: Thirty-five individuals underwent MT (4%). Both systems demonstrated prognostic value, though the 3-tier system proved superior, with OR 9.23 (3.42-23.69), PPV 0.152, NPV 0.98, compared to binary OR 3.49 (1.79-6.79), PPV 0.079, NPV 0.976. Interobserver agreement was also superior in the 3-tier system (0.47, p < 0.05) compared to the binary system (0.139, p = 0.39). Combining the two systems enhanced prognostic values (OR 14.28, PPV 0.217, NPV 0.981). CONCLUSION: The 3-tier system presented superior prognostic value to the binary system. Combining both systems to double-grade intermediate lesions might enhance risk assessment.

Association between autoimmune rheumatic diseases and head and neck cancer: Systematic review and meta-analysis.

BACKGROUND: Personal history of autoimmune rheumatic diseases has been implicated in the development of malignant neoplasms. Our aim was to assess the risk of head and neck (H&N) cancers in patients with autoimmune rheumatic diseases. METHODS: The articles search included PubMed, EMBASE, LILACS, The Cochrane Library, CINAHL, Scopus, Web of Science, and Google Scholar with no language restrictions for studies published from inception of the databases to August 20, 2022, assessing the risk of H&N cancer in patients with autoimmune rheumatic diseases. Studies were included if they reported the standardized incidence ratio (SIR) with corresponding 95% confidence intervals (CIs). The primary outcome was risk of H&N cancers in patients with autoimmune rheumatic diseases compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of H&N cancers varied according to study site. RESULTS: Our search identified 5378 records, of which 32 cohort studies were eligible for systematic review and 24 for meta-analysis (including 273 613 patients). A significant association was found between H&N cancer and autoimmune rheumatic diseases (SIR = 2.35; 95% CI: 1.57-3.50; p < 0.01, I2  = 94%). CONCLUSION: Our study suggests that patients with autoimmune rheumatic diseases had a significantly increased risk of H&N cancer compared with the general population, including thyroid, oral, and nasopharyngeal cancers. These findings have implications for the individualized screening of these patients and the planning of oncology units. The protocol is registered with PROSPERO, number CRD42020197827.

Oral squamous cell carcinoma arising from chronic traumatic ulcers.

BACKGROUND: A proportion of oral squamous cell carcinoma (OSCC) is preceded by oral potentially malignant disorders (OPMD), and the rest might not be associated with any well-established OPMD. Chronic traumatic ulcer (CTU) has been suggested as a lesion with potential for malignant transformation, but the evidence is inconclusive. OBJECTIVE: The aim of this study was to describe clinicopathological features of non-healing CTU (NHCTU) that later developed to OSCC. MATERIALS AND METHODS: A retrospective cohort study was performed of patients attending the Facultad de Odontología Universidad Nacional de Córdoba (2013-2019). The study included patients with a provisional diagnosis of CTU. CTUs without complete healing after removal of traumatic factors-non healing CTU (NHCTU)-were investigated by biopsy. A detailed description of cases where a malignancy was diagnosed is presented. RESULTS: A total of 107 CTU were included. Of these, 32 CTUs were considered NHCTU and two cases showed histological features of OSCC in the background of NHCTU. In both cases, lesions were found on the lateral tongue. Both were non smoking, non alcohol drinking individuals. Absence of any well-known OPMD was also registered. CONCLUSIONS: The possibility of malignant transformation in a subset of tongue NHCTU should not be underestimated. CLINICAL RELEVANCE: In a subgroup of patients, NHCTU could be considered an OPMD. Although the potential malignant transformation rate is low, these conditions should be always followed up.

Comparison of tobacco and alcohol consumption in young and older patients with oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: To compare the proportion of young (up to 45 years of age) and older (over 45 years of age) oral squamous cell carcinoma (OSCC) patients who report tobacco and alcohol consumption. METHODS: Observational studies reporting tobacco and alcohol consumption among young and older OSCC patients were selected in a two-phase process. Search strategies were conducted on five main electronic databases and complemented by grey literature. The risk of bias was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated with the software R Statistics version 4.0.2 (The R Foundation). RESULTS: From 6675 records identified, 38 studies met the eligibility criteria and were selected for qualitative synthesis and meta-analysis, encompassing 2439 young and 13,393 older patients. Tobacco smoking was reported by 39.5% (confidence interval (CI) = 31.7% to 47.9%, I2 = 78%) of the young patients and 48.4% (CI = 37.8% to 59.2%, I2 = 94%) of the older patients. Alcohol consumption was reported by 30.9% (CI = 22.7% to 40.5%, I2 = 83%) of the young and 45.8% (CI = 35.6% to 56.5%, I2 = 95%) of the older patients (P < 0.05). CONCLUSION: The comparison in the proportion of individuals reporting tobacco and alcohol consumption demonstrated that these habits were more prevalent in the older group (48.4% and 45.8% respectively) than in the young group (39.5% and 30.9%, respectively). CLINICAL RELEVANCE: As a significant proportion of patients with OSCC reported no habits, novel risk factors for OSCC need to be investigated in further research.

Chronic mechanical irritation enhances the effect of tobacco and alcohol on the risk of oral squamous cell carcinoma: a case-control study in Argentina.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is a multifactorial disease. The individual effect of each risk factor for OSCC may be conditioned by the frequency of other factors. The objective of this study was to identify the association between chronic mechanical irritation (CMI) and OSCC and to analyse the influence of CMI on other important risk factors for OSCC. MATERIALS AND METHODS: A prospective and age/sex-matched case-control study was performed in two institutions from Argentina between 2009 and 2019, with consecutive and newly diagnosed OSCC. The frequencies of tobacco, alcohol, and CMI were analysed using conditional logistic regression. Cumulative tobacco consumption and the presence of CMI were analysed using the Mann-Whitney test. RESULTS: CMI and OSCC were associated with an OR of 7.02 (95% CI 3.57-13.78, p < 0.001). The combination of CMI and alcohol demonstrated the highest risk of OSCC (OR 53.83, CI 95% 8.04-360, p < 0.0001), followed by the combination of CMI, tobacco, and alcohol (OR 48.06, CI 95% 8.47-272, p < 0.0001). The combination of CMI and tobacco was also significant (OR 5.61, CI 95% 1.07-29.54, p = 0.042). Patients with CMI developed OSCC with less cumulative tobacco use compared with those without CMI. CONCLUSION: CMI is an independent risk factor for OSCC, and it could act as a risk modifier among tobacco and alcohol users having an enhancing effect. CLINICAL RELEVANCE: Elimination of CMI could decrease the risk of OSCC.

Reexamination of delays in diagnosis of oral cancer following an intervention program in Cordoba, Argentina.

OBJECTIVE: We compare the results of delay in oral cancer diagnosis before and after a campaign directed toward dentists and raising awareness of the population to achieve early diagnosis of oral cancer in Córdoba, Argentina. The campaign included training dentists in diagnostic skills and a public awareness program through media and networks. STUDY DESIGN: Clinical records (period 1: before intervention program, n = 70; period 2: after intervention program, n = 60) of patients presenting with oral squamous cell carcinoma treated in 2 referral centers were analyzed. Records included first symptoms, first consultation with a health professional, and the time when treatment was formulated. RESULTS: Oral cancer diagnosis at early stages increased from 27% (period 1) to 40% (period 2). Biopsy at first consultation was indicated in 6% of patients in period 1 and in 23.3% in period 2 (odds ratio = 4.68; 95% confidence interval, 1.87-11.73; P < .05). Professional delay at early stage decreased from 72% in period 1 to 36.8% in period 2. During period 1, for initial stage cancer, the average patient and professional delays were 2.7 and 2.9 months, respectively (P = .06); in period 2, patient delay was 2.67 months and professional delay was 1.34 months (P = .005). CONCLUSION: The intervention program helped to improve early-stage diagnosis from 27% to 40% by reducing professional delays.

Prognostic and clinicopathological significance of podoplanin immunoexpression in oral and oropharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: Podoplanin (PDPN) is a glycoprotein associated with epithelial-mesenchymal transition, invasion, and metastasis in several types of malignancies, including oral and oropharyngeal squamous cell carcinoma (OSCC). The aim of this systematic review (SR) was to summarize and critically appraise the available evidence about the association between PDPN immunoexpression and clinicopathological features and its utility as a prognostic marker in OSCC. METHODS: Five electronic databases and three gray literature databases were searched for immunohistochemical studies, which were selected in a two-phase process. RESULTS: From 721 records identified, 22 cohort and seven analytical cross-sectional studies were included. Few studies reported that PDPN expression was associated with poorer survival rates in OSCC: overall survival = 4/12, disease-free survival = 4/7, and cancer-specific survival = 2/4 studies. Positive associations were most frequently reported on lymph node involvement, higher histopathological grade, and advanced clinical stages. CONCLUSION: Within limitations of this SR, PDPN may be associated with lymph node involvement, histopathological grade, and clinical stage of OSCC. Current evidence suggests that PDPN could be a useful prognostic marker for OSCC that needs further exploration.

Lichenoid proliferative leukoplakia, lichenoid lesions with evolution to proliferative leukoplakia or a continuum of the same precancerous condition? A revised hypothesis.

BACKGROUND: Multiple white plaques of the oral mucosa are usually associated with potentially malignant disorders such as oral lichen planus, oral lichenoid lesions and proliferative verrucous leukoplakia. Previous studies in the current literature describe a potential clinical overlap in these entities. The aim of this study is to review clinicopathological and evolutive features of these Oral Potentially Malignant Disorders highlighting the dynamic changes of diagnoses. DISCUSSION: It was previously hypothesized that a subset of patients with oral lichen planus or oral lichenoid diagnosis, could develop multiple white plaques during the natural history of the disease, fulfilling diagnostic criteria for proliferative verrucous leukoplakia. Consequently, these entities could, under certain conditions, obey a continuum of the same precancerous condition in the context of the field cancerization theory, increasing the risk of malignant transformation. Nevertheless, there is limited scientific evidence concerning this issue. CONCLUSION: Further studies are needed to understand the biological and evolutive features of the link between these oral potentially malignant disorders. Regardless of its diagnosis, these patients with multifocal white lesions must be carefully monitored to detect early malignant transformation.

Prognostic biomarkers for malignant transformation of oral potentially malignant disorders: a scoping review protocol.

OBJECTIVE: This scoping review aims to identify and systematically map the available evidence concerning the prognostic biomarkers for malignant transformation of oral potentially malignant disorders (OPMDs), and to identify and analyze possible knowledge gaps in this field of literature. INTRODUCTION: It is hypothesized that diagnosis and treatment of oral cancer in its early stages may be the key to improving the prognosis and reducing treatment-related consequences. Oral potentially malignant disorders represent tissue alterations with a higher risk of malignant transformation compared to the normal mucosa. Therefore, the study of prognostic biomarkers for OPMD could represent new diagnosis and therapeutic targets and, consequently, contribute to the reduction of oral cancer burden worldwide. INCLUSION CRITERIA: Longitudinal studies investigating prognostic biomarkers regarding the malignant transformation of OPMD will be included. The initial OPMD diagnosis and the malignant transformation must have been confirmed by histopathological analysis. To achieve minimal heterogeneity, studies that assess biomarkers in other locations (blood, plasma or others) will be excluded. METHODS: Five electronic databases and three grey literature databases will be consulted. No restrictions regarding publication date will be applied. Only studies published in the Latin (Roman) alphabet, which comprises most of the European languages, will be included. Study selection will be performed by two authors in a two-phase process; if any disagreement arises, a third author will be consulted to make a final decision. Data extraction will be performed by two authors using a standardized extraction tool. The results will be described in details accordantly with the aims of this scoping review.

The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: This systematic review (SR) aimed to summarise and critically appraise available evidence about the association between the synergistic consumption of alcohol and tobacco and the occurrence of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Observational studies investigating the association between the synergistic consumption of alcohol and tobacco and OSCC occurrence were included. Studies were selected in a two-phase process and searches were conducted on five main electronic databases, complemented by three grey literature databases. RESULTS: From 3260 records identified, 33 articles were included for qualitative analysis, of which 15 were included in the meta-analyses. Overall, the synergistic consumption was positively associated with the occurrence of OSCC (odds ratio [OR] = 5.37; 95% confidence interval [95%CI] = 3.54-8.14). Increased odds for OSCC occurrence were observed regarding the synergistic consumption of alcohol and smoked tobacco (OR = 4.74; 95%CI = 3.51-6.40), alcohol and smokeless tobacco (OR = 7.78; 95%CI = 2.86-21.14), and alcohol, smoked tobacco, and smokeless tobacco (OR = 16.17; 95%CI = 7.97-32.79). CONCLUSIONS: According to the results of this SR, the synergistic consumption of alcohol and tobacco (both smoked and smokeless) significantly increased the odds for the occurrence of OSCC. CLINICAL RELEVANCE: The knowledge provided by this SR may be useful for a better understanding of differences in the effect of synergistic consumption of alcohol and tobacco products in OSCC development. These data might aid healthcare authorities to develop measures for tobacco and alcohol control considering the needs of their population.

Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis.

Oral potentially malignant disorders (OPMD) are chronic conditions, which have a higher risk of transformation to oral squamous cell carcinoma. The aim of this systematic review and meta-analysis was to answer the question: "What is the prevalence of oral potentially malignant disorders among adults?" Studies reporting the prevalence of these conditions (leukoplakia, erythroplakia, oral submucous fibrosis [OSMF], and actinic cheilitis) were selected, only studies in which a clinical assessment and histopathological confirmation were performed were included. Of the 5513 studies, 22 met the inclusion criteria for qualitative and quantitative analyses. The risk of bias (RoB) of the selected studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Seven studies were classified as high risk, 12 as moderate risk, and 3 as low RoB. The meta-analysis showed that the prevalence of OPMD was 4.47% (95% CI = 2.43-7.08). The most prevalent OPMDs were OSMF (4.96%; 95% CI = 2.28-8.62) and leukoplakia (4.11%; 95% CI = 1.98-6.97). OPMDs were identified more commonly in males (59.99%; 95% CI = 41.27-77.30). Asian and South American/Caribbean populations had the highest prevalence rates of 10.54% (95% CI = 4.60-18.55) and 3.93% (95% CI = 2.43-5.77), respectively. The overall prevalence of OPMD worldwide was 4.47%, and males were more frequently affected by these disorders. The prevalence of OPMD differs between populations; therefore, further population-based studies may contribute to the better understanding of these differences.

Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory.

Despite commendable progress in the prevention, detection, and treatment of a wide variety of solid tumor types, oral squamous cell carcinoma (OSCC) remains a significant health burden across the globe. OSCC carcinogenesis involves accumulation of genetic alterations that coincide with the multistep malignant transformation of normal oral epithelium. OSCC is often first diagnosed at late stages of the disease (advanced regional disease and/or metastasis). Delayed diagnosis precludes successful treatment and favorable outcomes. In clinical practice, opportunities exist to identify patients with oral potentially malignant disorders (OPMDs), which precede the development of cancer. This review addresses the current status of laboratory and clinical research on OPMDs, with emphasis on leukoplakia and erythroplakia. OSF is also presented, though there is a paucity of published studies on this disorder. We focus on findings that could translate into earlier diagnosis and more efficacious treatment of those lesions with significant malignant potential. We explore how markers of OPMD malignant transformation might be implemented into current diagnostic practice to help clinicians objectively stratify patients into treatment/follow-up groups according to relative risk. We provide an overview of recently concluded and ongoing OPMD chemoprevention trials. We describe laboratory OPMD models that can be used to not only to reveal the genetic and molecular intricacies of oral cancer but also to develop novel screening methods and therapeutic approaches. Finally, we call for targeted screening programs of at-risk populations in order to facilitate diagnosis and treatment of OPMD and early OSCC.

Biomarkers to predict oral squamous cell carcinoma in precancerous stages

There have been many attempts to establish biomarkers in order to determine the susceptibility of some normal human tissues to undergo malignant change. However, definitive markers for oral squamous cell carcinoma have not been yet achieved. Amongst some of the most promising molecular biomarkers, there is a respectful amount of literature produced on p53, both in human tissue fluids and in biopsies of potentially malignant lesions, 3p gene deletions, and, most recently, image-based ploidy analysis of tissue specimens.. In spite of the experimental character and speculative results of all those novel techniques, the image-based ploidy analysis appears to be the most sensitive and reliable method to predict malignant transformation in potentially malignant lesions of the oral mucosa