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 epidemiological profile of burning mouth syndrome patients following the International Headache Society classification: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to determine the clinical and epidemiologic profile of patients with burning mouth syndrome (BMS) following the current classification of the International Headache Society (IHS)-the International Classification of Headache Disorders (ICHD-3) and the International Classification of Orofacial Pain (ICOP). STUDY DESIGN: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and involved a comprehensive search on PubMed, Scopus, EMBASE, Web of Science, LILACS, and the gray literature. RESULTS: Of the 4,252 studies identified, 41 were included. In general, there were no differences between the clinical and epidemiologic profiles of patients with BMS classified based on ICHD-3 or ICOP. Studies were pooled in meta-analyses and showed a significant prevalence of female patients between the sixth and seventh decade of life. The burning sensation and the tongue were the most prevalent descriptors and affected location. Significant associations were demonstrated between BMS and anxiety (P = .0006), depression (P = .004), and poor oral hygiene (P = .00001). CONCLUSIONS: Under the existing contemporary classification systems, patients with BMS were found to be mostly females in the sixth and seventh decade of life with a burning sensation on the tongue. Experiencing depression and anxiety was a commonly existing comorbidity.

Prevalence and clinical characteristics of oral lesions in heart transplant patients induced by sirolimus and everolimus: a systematic review and meta-analysis on a global scale.

OBJECTIVE: Sirolimus (SRL) and everolimus (EVL) are increasingly included in immunosuppressive protocols after heart transplantation. They present some side effects, including the appearance of painful lesions in the oral cavity. Therefore, this systematic review aimed to verify the global prevalence and clinical characteristics of oral lesions induced by SRL and EVL in heart transplant patients. STUDY DESIGN: A systematic review was performed using 5 main electronic databases (Medline/PubMed, SCOPUS, EMBASE, Web of Science, and LILACS), in addition to the gray literature. Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the Joanna Briggs Institute appraisal tools, and the certainty of evidence was evaluated through GRADE assessment. RESULTS: Seventeen studies (860 patients) were included in the qualitative analysis. Of these, 11 studies were pooled in a meta-analysis of prevalence. The worldwide prevalence of oral lesions induced by SRL and EVL in heart transplant patients was 10.0%, and most lesions were described as ulcers >1.0 cm, related to significant pain. CONCLUSIONS: Oral lesions induced by SRL and/or EVL, although not very prevalent, have a relevant impact on patient's lives and the continuity of treatment.

Cell block preparation as an adjunctive tool after fine-needle aspiration cytology for screening oral and maxillofacial diseases.

OBJECTIVE: To describe the use of cell block (CB) preparation from fine-needle aspiration cytology for diagnosing oral and maxillofacial diseases. STUDY DESIGN: We performed a retrospective analysis of 568 samples collected by our laboratory for CB preparation from fine-needle aspiration cytology of the oral and maxillofacial region between January 2001 and October 2021. We performed cytologic diagnoses and compared them with the available histopathologic diagnoses to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CB preparation for identifying malignant lesions. RESULTS: The most frequent diagnosis was pleomorphic adenoma (n = 44, 7.7%), followed by metastatic squamous-cell carcinoma (n = 28, 4.9%) and odontogenic keratocyst (n = 26, 4.6%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CB preparation, which revealed detailed morphologic and architectural patterns, were 70.0%, 100.0%, 100.0%, 62.5%, and 80.0%, respectively. CONCLUSIONS: Cell block preparation from fine-needle aspiration cytology of the oral and maxillofacial region may be a useful adjunctive diagnostic tool for diagnosing oral and maxillofacial diseases because it reveals morphologic and architectural patterns similar to those shown on histopathologic slides, leading to the better categorization of diseases.

Clinicopathological study and survival outcomes of sialoblastoma: A systematic review.

Sialoblastoma is a rare malignant salivary gland tumor. The aim of this study was to review the available published data on sialoblastoma in a comprehensive analysis of its clinicopathologic characteristics, treatment, and outcomes. An unrestricted electronic search was performed in the following databases: MEDLINE/PubMed, EMBASE, Scopus, Web of science, and gray literature databases. Eligibility criteria included publications with sufficient clinical, imaging, and histopathological information to confirm the diagnosis of sialoblastoma. Data were evaluated descriptively and analytically. A total of 52 studies met the eligibility criteria. In total, 62 patients were evaluated. There was no gender predilection, with the parotid being the most affected primary site (n = 28; 45.2%). In the log-rank test, there was a significant increase in disease-associated survival in patients younger than 1 year of age (82.8% vs. 44.4%; p = 0.003), individuals with lesions in major salivary glands (79.4% vs. 38.5%; p = 0.005), patients without metastases (77.8% vs. 14.3%; p = 0.011), encapsulated lesions (85.7% vs. 0%; p < 0.0001), congenital lesions (83.3% vs. 25.0%; p < 0.0001), and lesions that do not show perineural invasion (89.5% vs. 40%; p = 0.035). Kaplan-Meier curves estimated overall survival and disease-free survival at 5 years of 95.5% and 68.1%, respectively. In the multivariate Cox regression model, only the presence of metastasis was identified as an independent prognostic factor (hazard ratio [HR] = 9.81; p = 0.010). Although sialoblastoma presents good prognosis, the tumor has a high recurrence rate.

Machine learning for the prediction of toxicities from head and neck cancer treatment: A systematic review with meta-analysis.

INTRODUCTION: The aim of the present systematic review (SR) is to summarize Machine Learning (ML) models currently used to predict head and neck cancer (HNC) treatment-related toxicities, and to understand the impact of image biomarkers (IBMs) in prediction models (PMs). The present SR was conducted following the guidelines of the PRISMA 2022 and registered in PROSPERO database (CRD42020219304). METHODS: The acronym PICOS was used to develop the focused review question (Can PMs accurately predict HNC treatment toxicities?) and the eligibility criteria. The inclusion criteria enrolled Prediction Model Studies (PMSs) with patient cohorts that were treated for HNC and developed toxicities. Electronic database search encompassed PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, LILACS, and Gray Literature (Google Scholar and ProQuest). Risk of Bias (RoB) was assessed through PROBAST and the results were synthesized based on the data format (with and without IBMs) to allow comparison. RESULTS: A total of 28 studies and 4,713 patients were included. Xerostomia was the most frequently investigated toxicity (17; 60.71 %). Sixteen (57.14 %) studies reported using radiomics features in combination with clinical or dosimetrics/dosiomics for modelling. High RoB was identified in 23 studies. Meta-analysis (MA) showed an area under the receiver operating characteristics curve (AUROC) of 0.82 for models with IBMs and 0.81 for models without IBMs (p value < 0.001), demonstrating no difference among IBM- and non-IBM-based models. DISCUSSION: The development of a PM based on sample-specific features represents patient selection bias and may affect a model's performance. Heterogeneity of the studies as well as non-standardized metrics prevent proper comparison of studies, and the absence of an independent/external test does not allow the evaluation of the model's generalization ability. CONCLUSION: IBM-featured PMs are not superior to PMs based on non-IBM predictors. The evidence was appraised as of low certainty.

Epithelial salivary gland tumors in pediatric patients: An international collaborative study.

OBJECTIVE: Salivary gland tumors (SGT) are a diverse group of uncommon neoplasms that are rare in pediatric patients. This study aimed to characterize the clinicopathological profile of pediatric patients affected by SGT from a large case series derived from an international group of academic centers. STUDY DESIGN: A retrospective analysis of pediatric patients with SGT (0-19 years old) diagnosed between 2000 and 2021 from Brazil, South Africa, and the United Kingdom was performed. SPSS Statistics for Windows was used for a quantitative analysis of the data, with a descriptive analysis of the clinicopathological characteristics and the association between clinical variables and diagnoses. RESULTS: A total of 203 cases of epithelial SGT were included. Females were slightly more commonly (56.5%), with a mean age of 14.1 years. The palate was the most common site (43.5%), followed by the parotid gland (29%), lip (10%), and submandibular gland (7.5%). The predominant clinical presentation was a flesh-colored, smooth, and painless nodule. Pleomorphic adenoma (PA) was the most frequently diagnosed SGT (58.6%), followed by mucoepidermoid carcinoma (MEC) (26.6%). Surgery (90.8%) was the favored treatment option. CONCLUSIONS: Benign SGT in pediatric patients are more commonly benign than malignant tumors. Clinicians should keep PA and MEC in mind when assessing nodular lesions of possible salivary gland origin in pediatric patients.

Clinical outcomes of dental implants in head and neck cancer patients: An overview.

OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of dental implants (DIs) in patients with head and neck cancer (HNC) treated with radiotherapy (RT), isolated chemotherapy, or bone modifying agents (BMAs). STUDY DESIGN: This study was registered in the Prospective Register of Systematic Reviews (CRD42018102772); conducted via the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist; and based on PubMed, Scopus, Embase, Cochrane Library, Web of Science, and gray literature searches. The selection of studies was performed in 2 phases by 2 independent reviewers. The risk of bias (RoB) was assessed by the Measurement Tool to Assess the Methodological Quality of Systematic Reviews 2. RESULTS: Twenty systematic reviews were included in the qualitative analysis. The majority scored as having high RoB (n = 11). Primary DIs placement in the mandible of patients with HNC subjected to RT doses <50 Gy was associated with better survival rates. CONCLUSIONS: The placements of DIs could be considered safe in patients with HNC in sites of alveolar bone that received RT (≤5000 Gy); however, no conclusions could be made in patients with cancer managed by chemotherapy or BMAs. Due to the heterogeneity of studies included, the recommendation for DIs placement in patients with cancer should be carefully considered. Future better controlled randomized clinical trials are required to provide enhanced clinical guidelines for best patient care.

Dosimetric parameters and radiotherapy simulation methods used in preclinical studies of radiation damage to the dentition: a systematic review.

OBJECTIVE: This systematic review investigated the dosimetric parameters used in preclinical studies. STUDY DESIGN: Searches were performed in 3 databases (PubMed, Scopus, and Embase) and gray literature to identify studies for review. In vitro and ex vivo studies that examined the effect of radiation on human permanent teeth were included. The modified Consolidated Standards Of Reporting Trials checklist of items for reporting preclinical in vitro studies was used to assess the risk of bias. RESULTS: In total, 32 studies met the inclusion criteria. The average radiation dose of in vitro studies was 53 (±22) Gy and in ex vivo studies was 69 (±1) Gy. Twenty-two studies used 5 different fractionation schemes. Twenty-two of the included studies did not report the radiotherapy modality of those reporting. Twenty studies used linear accelerators, and 7 used Cobalt-60 with the source-surface-distance of radiation ranging from 1.5 to 100 cm. Distilled water was the storage solution for the dental structure used most commonly. Biases were observed, including small sample sizes, lack of randomization, and blinding processes. CONCLUSION: The dosimetric parameters used in the preclinical studies, including radiation dose, radiotherapy modality, fractionation regime, and the storage solutions used did not support the hypothesis of direct effects of radiation on the dental structure.

Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review.

OBJECTIVE: This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information. STUDY DESIGN: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. RESULTS: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. CONCLUSION: Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.

Tongue hamartomas in pediatric patients: an international case series and literature review.

This study reports 9 additional tongue hamartomas in children paired with a literature review. A retrospective analysis was performed from 3 Oral Pathology laboratories. Additionally, a literature review was conducted through 5 electronic databases and gray literature. A total of 9 cases were identified in the retrospective analysis. Females outnumbered males with a ratio of 1.25:1. The age of presentation ranged from 2 weeks to 7 years. The posterior dorsum tongue was the most affected subsite (n = 4). One case was seen in a patient with oro-facial-digital syndrome, 2 cases in patients with cleft palates, and one case with an encephalocele. The most common predominant component was salivary gland tissue (n = 4). A literature search included 79 pediatric patients presenting with 95 tongue hamartomas. A slight female (n = 47) predilection was observed, with ages varying from 15 hours to 19 years. The posterior tongue dorsum (n = 31) was the most affected site. Seven cases were seen in association with syndromes. The most common predominant component was smooth muscle (n = 35). Although hamartomas are rare in the oral cavity, they should be considered in the differential diagnosis of masses involving the posterior tongue dorsum in children.

Systemic conditions associated with increased risk to develop oral squamous cell carcinoma: Systematic review and meta-analysis.

This study aimed to map systemic alterations predisposing to oral squamous cell carcinoma (OSCC) onset. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Five databases were used to access (1) reports of OSCC co-occurring in patients with systemic conditions, (2) prevalence of OSCC among these patients, and (3) clinicopathological profiles. Data from more than 1 million patients worldwide showed that Fanconi's anemia, xeroderma pigmentosum, dyskeratosis congenital, chronic fatigue syndrome, and patients post bone marrow transplantation (BMT) present increased risk for OSCC development. The overall prevalence of OSCC in syndromic patients and post-BMT were 0.65% (95% CI = 0.13-3.11, p < 0.01) and 5.83% (95% CI = 0.00-30.90, p < 0.01), respectively. The certainty of the evidence was moderate. This study demonstrated that some systemic conditions predispose to OSCC. These results present an impact on the screening of OSCC in systemically compromised patients.

To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis.

PURPOSE: Teeth with poor prognosis are generally recommended to be extracted prior to head and neck radiotherapy (RT) to reduce the risk of developing osteoradionecrosis (ORN), although controversies have been reported. The present systematic review aimed to determine whether tooth extraction prior to head and neck RT may be associated with a reduced risk of developing ORN compared to dental extraction during or after RT. METHODS: The review protocol was registered in PROSPERO (CRD42021241631). The review was reported according to the PRISMA checklist and involved a comprehensive search of PubMed, Scopus, Embase, Cochrane Library, LILACS, and Web of Science, in addition to the gray literature. The selection of studies was performed in two phases by two reviewers independently. The risk of bias of individual studies was analyzed using the Joanna Briggs Institute checklist for cross-sectional studies, and the certainty of evidence was assessed using the GRADE tool. RESULTS: Twenty-eight observational studies were included in the qualitative synthesis, which showed substantial heterogeneity regarding the association between the timing of tooth extraction and ORN development. Twenty-seven of 28 studies were pooled in a meta-analysis that demonstrated a significant association between an increased risk of ORN and post-RT tooth extraction (odds ratio: 1.98; 95% CI: 1.17-3.35; p = 0.01). CONCLUSION: It was confirmed with moderate certainty that dental extractions should be performed prior to the start of head and neck RT to reduce the risk of ORN.

Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study.

BACKGROUND: Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. METHODS: This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. RESULTS: A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin's tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours. CONCLUSIONS: This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population

Background: Lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC) represent a major health problem in the global scenario. In South America, the highest incidence rates are seen in Brazil. Therefore, the epidemiological and clinical profile and survival outcomes of lip, oral cavity, and oropharyngeal SCC was studied in São Paulo State, Brazil. Material and Methods: The clinicopathological data of 12,099 patients with lip, oral cavity, and oropharyngeal SCC were obtained from hospital cancer registries of the Fundação Oncocentro de São Paulo, Brazil (2010–2015). Survival rates and other analyses were performed using SPSS software. Results: A clear male predominance was observed, particularly for patients with oropharyngeal SCC (88.3%). The average age of patients was higher for lip cases (65 ± 13.5 years) compared to other sites. The schooling level was low for most patients, especially in lip cases (87.9%). Most of the patients with oral cavity (71.8%) and oropharyngeal (86.3%) SCC had advanced-stage (III–IV) disease. However, the majority of lip cases (83.3%) were at an early stage (I–II). Surgical excision was the main treatment for lip (72%) and oral cavity SCC (23.5%), and chemoradiotherapy was the main treatment for oropharyngeal SCC (40.2%). The 5-year overall survival (OS) for patients with lip, oral cavity, and oropharyngeal SCC were 66.3, 30.9, and 22.6%, respectively. Multivariate analysis revealed that the determinants of OS were different for lip, oral cavity, and oropharyngeal SCC, except for those at the clinical stage, which was an independent predictor for all sites. Conclusions: OS-independent determinants varied according to the affected site. Oral cavity and oropharyngeal SCC presented worse survival rates than those for lip SCC.(AU)

Clinical manifestations of head and neck cancer in pediatric patients, an analysis of 253 cases in a single Brazilian center

Background: Pediatric head and neck cancer (PHNC) is rare and its nonspecific clinical manifestations may often lead to delayed diagnosis. We aimed to describe the signs, symptoms, and clinicopathological characteristics of PHNC. Material and Methods: Medical records were retrospectively reviewed for all PHNC cases diagnosed from 1986 to 2016 affecting patients aged 19-years and younger from a tertiary referral center in Brazil. Demographic variables, anatomical site of primary tumors, histopathological diagnoses, signs and symptoms, and patterns of misdiagnosis were collected and interpreted by statistical and descriptive analysis. Results: A total of 253 PHNC cases were included. The mean age was 9.3 years and male patients were more frequently affected (60.9%). Burkitt lymphoma (23.7%), nasopharyngeal carcinoma (15.8%), and rhabdomyosarcoma (15.4%) were the most common cancer types. The nasopharynx (28.9%), cervical/lymph node region (25.3%), and craniofacial bones (8.3%) were the predominant anatomical sites. Tumor/swelling (68.4%), was the clinical finding often presented. The univariable analysis showed association between tumor histology and clinical variables such as sex (p=0.022), age (p<0.0001), anatomical location (p<0.0001) tumor/swelling (p=0.034), pain (p=0.031), systemic/general manifestations (p=0.004), nasal/breathing alterations (p=0.012), orbital/ocular alterations (p<0.0001). Misdiagnosis such as tonsillitis, otitis, and abscess were frequent. Conclusions: Although the clinical findings of PHNC are often unspecific, this study provided signs and symptoms with significant correlations between tumor histology. The suspicion of malignancy should be considered when the main signs and symptoms reported here appear and persist, in order to conduct a timely diagnosis.(AU)

Impact of the COVID-19 pandemic on public University laboratories of oral and maxillofacial pathology: A Brazilian multicenter study.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on the number of diagnoses of oral and maxillofacial lesions in public laboratories after one year of COVID-19 outbreak in Brazil. MATERIAL AND METHODS: This is a cross-sectional study. Biopsies submitted to histopathologic examination from March 2019 to February 2020 (pre-pandemic period) and from April 2020 to March 2021 (pandemic period) in nine Brazilian public oral pathology laboratories were retrieved and the number of diagnoses, types of lesion, and percentage changes during both periods were analyzed. RESULTS: There were 7389 diagnoses in the pre-pandemic period and 2728 in the pandemic era, indicating a reduction of 63.08%. The reduction was 64.23% for benign lesions and 49.48% for malignant lesions, with a 50.64% reduction in squamous cell carcinoma. The largest decreases were observed in April 2020 and January 2021. CONCLUSION: An important reduction in the diagnoses of benign and malignant lesions was noted in the Brazilian public oral pathology laboratories during the first year of the COVID-19 pandemic.