Potential Single Nucleotide Polymorphisms markers for radiation dermatitis in head and neck cancer patients: a meta-analysis.

PURPOSE: To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD. METHODS: This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE. RESULTS: Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFß1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with a similar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed a statistically significant association with very low certainty of evidence. CONCLUSION: The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be a promising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have a customized treatment. This current review provides new research directions.

Burning mouth in oncology care: a systematic review.

Burning mouth, also referred to as oral dysesthesia, is an underreported condition among cancer patients that may represent an early symptom of cancer or an adverse effect of treatment. This review sought to characterize this symptom in oncology care where burning symptoms may occur. A systematic review of the literature was performed based on the PRISMA statement, and the protocol was registered at PROSPERO database. A structured search was done using eight databases. The process of study selection was conducted in two distinct phases. The JBI Critical Appraisal Tools were utilized to evaluate the risk of bias in the studies included. Of the total number of studies assessed, sixteen met the eligibility criteria. Of these studies included, 7 were case reports, 7 cross-sectional studies, and 2 non-randomized clinical trials. Most studies presented low risk of bias (n = 9), while the remaining studies were evaluated and scored as moderate (n = 5) or high (n = 2) risk of bias. Burning mouth was reported as a first symptom of cancer in three studies, and as an adverse event of radiotherapy (n = 2), chemoradiotherapy (n = 2), and chemotherapy (n = 9). Burning mouth was a first symptom in 0.62% of oral squamous cell carcinoma (OSCC), and 3.3% of patients with pain as chief complaint. Oral dysesthesia prevalence was 13.6% in patients experiencing chemotherapy-induced oral adverse events. The symptom of burning mouth should be examined in oncology care, as it may be underreported and therefore undertreated. New therapies may be related to a higher risk of oral burning and studies assessing approach to management are needed. Current management borrows from the current management of burning mouth in the non-cancer setting.

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.

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.

Impact of head and neck radiotherapy on the longevity of dental adhesive restorations: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Established restorative protocols for patients after head and neck radiotherapy are lacking, increasing the failure rates of dental adhesive restorations. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the evidence regarding the impact of head and neck radiotherapy on the longevity of dental adhesive restorations. MATERIAL AND METHODS: A search was performed using PubMed, Scopus, and Embase in May 2018 (updated in November 2020). Data extraction was performed regarding the percentage of restoration failure among dental adhesive materials, including glass ionomer cements, resin-modified glass ionomer cements, and composite resins. Risk of bias was assessed by the meta-analysis of statistics assessment and review instrument (MAStARI). Confidence in cumulative evidence was evaluated by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. RESULTS: Four studies met the inclusion criteria. All included studies were classified as having a moderate risk of bias and reported results regarding class V restorations. Overall, composite resins presented lower failure rates at 2 years (30%) when compared with resin-modified glass ionomer (41%) and glass ionomer cements (57%). Meta-analysis showed that the risk of failure with glass ionomer cements was greater than with resin-modified glass ionomer cements (RR: 1.71, P<.001). Composite resins presented lower risk of failure when compared with glass ionomer (RR: 2.29, P<.001) and resin-modified glass ionomer cements (RR: 1.30, P=.03). Three studies reported results regarding fluoride compliance, which had a negative effect on the survival rates of glass ionomer and resin-modified glass ionomer cements and a positive effect on composite resin restorations. CONCLUSIONS: The results suggest that composite resin restorations associated with fluoride gel compliance seems to be the best alternative for restoring class V lesions in patients after head and neck radiotherapy. However, the results showed moderate certainty of evidence, which justifies the need for more randomized clinical trials regarding this subject.

Proteomic approaches to assist in diagnosis and prognosis of oral cancer.

Introduction: Oral squamous cell carcinoma (OSCC) ranks among the top 10 leading causes of cancer worldwide, with 5-year survival rate of about 50%, high lymph node metastasis, and relapse rates. The OSCC diagnosis, prognosis, and treatment are mostly based on the clinical TNM classification. There is an urgent need for the discovery of biomarkers and therapeutic targets to assist in the clinical decision-making process.Areas covered: We summarize proteomic studies of the OSCC tumor, immune microenvironment, potential liquid biopsy sites, and post-translational modifications trying to retrieve information in the discovery and verification or (pre)validation phases. The search strategy was based on the combination of MeSH terms and expert refinement.Expert opinion: Untargeted combined with targeted proteomics are strategies that provide reliable and reproducible quantitation of proteins and are the methods of choice of many groups worldwide. Undoubtedly, proteomics has been contributing to the understanding of OSCC progression and uncovers potential candidates as biomarker or therapeutic targets. Nevertheless, none of these targets are available in the clinical practice yet. The scientific community needs to overcome the limitations by investing in robust experimental designs to strengthen the value of the findings, leveraging the translation of knowledge, and further supporting clinical decisions.

Binary and WHO dysplasia grading systems for the prediction of malignant transformation of oral leukoplakia and erythroplakia: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review was to examine the evidence of the binary histologic grading system capacity for predicting malignant transformation and to compare it with that of the WHO systems. MATERIAL AND METHODS: A systematic review was conducted, using PubMed, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO databases without any language or timeframe restrictions. Studies were included if they compared the binary and the WHO histologic grading systems in the prediction of malignant transformation of oral epithelial dysplasia (OED). RESULTS: The capacity of the WHO and binary grading systems to predict malignant transformation ranged from 16 to 80% and from 5 to 80%, respectively. The pooled malignant transformation rate of lesions classified as severe dysplasia or carcinoma in situ by the WHO grading was 40% (95% confidence interval (CI), 0.02-0.87; I2 = 92%; P = 0.00), while the corresponding value for lesions classified as high-risk by the binary grading system was 31% (95% CI, 0.00-0.84; I2 = 97%; P = 0.00). Overall, there was no significant difference in prognostication accuracy between the WHO and the binary systems (odds ratio = 2.02; 95% CI, 0.88-4.64). CONCLUSIONS: Although some studies suggest that the binary system is associated with lower inter-rater variability when grading OED, the evidence remains inconclusive on whether this system is superior to that of the WHO at predicting malignant transformation. CLINICAL RELEVANCE: The reproducibility of the binary system has the potential to be better for prognostic purposes. However, there is no high-quality evidence to confirm if this advantage may assist clinicians in decision-making.

Effects of oral supplementation in the management of oral mucositis in cancer patients: A meta-analysis of randomized clinical trials.

PURPOSE: To evaluate the effects of oral supplementation on the management of oral mucositis in patients with cancer undergoing chemo and/or radiation therapy. METHOD: This is a systematic review and meta-analysis. The search was performed at 6 databases, and in the gray literature. Methodology of included studies was evaluated by the Cochrane Collaboration Risk of Bias Tool, and evidence quality was assessed by GRADE instrument. RESULTS: Twelve randomized clinical trials were included in this review. The oral supplementation used was an oral elemental diet with amino acids and minerals (elental), glutamine, and zinc. The majority of the studies included in this review showed benefits in delaying the occurrence of OM by using glutamine and zinc, and in reducing the severity of OM with glutamine, zinc, and elental in patients receiving chemoradiotherapy. The meta-analysis showed that the risk of oral mucositis in the zinc group was slightly lower than in the control (RR: 0.71, 95% CI: 0.53-0.96, P = 0.02, n = 982) while the glutamine group presented the same risk as the control (RR: 0.91, 95% CI: 0.78-1.05, P = 0.19, n = 314). The evidence quality suggested low confidence for zinc and glutamine studies in the estimated effect from the outcomes assessed. CONCLUSIONS: Zinc is a promising strategy in the management of oral mucositis since it delayed the occurrence and reduced its severity. Glutamine and Elental, on the other hand, had no strong evidence in the prevention and/or treatment of oral mucositis in patients with cancer.

Impact of Clustering Oral Symptoms in the Pathogenesis of Radiation Caries: A Systematic Review.

Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described "clustering of oral symptoms theory," the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account.

Laser therapy for recurrent aphthous stomatitis: an overview.

OBJECTIVES: To evaluate therapeutic effects of laser therapy on patients with recurrent aphthous stomatitis assessing evidences from previously published systematic reviews. MATERIALS AND METHODS: An overview of systematic reviews was conducted based on PRISMA checklist. Search strategies were developed and adapted for six different electronic databases and a gray literature search was also performed. The methodology quality of the included systematic reviews was assessed by the Measurement Tool to Assess the Methodological Quality of Systematic Reviews 2 (AMSTAR 2). RESULTS: After a two-step selection, five systematic reviews were included. Methodology quality was considered as a high risk of bias in two systematic reviews, while in the other three were graded as moderate. The systematic reviews' conclusions demonstrated that all included systematics reviews showed positive effects of laser therapy for pain relief, and most of them demonstrated healing improvement. A meta-analysis was not feasible due to heterogeneity in treatments parameters. CONCLUSIONS: Evidence suggested that laser therapy is an effective tool to treat recurrent aphthous stomatitis; nevertheless, more randomized clinical trials should be conducted to compare different lasers parameters. CLINICAL RELEVANCE: The present overview evaluated recent evidence about laser therapy for recurrent aphthous stomatitis management in order to contribute for evidence-based dentistry and decision-making. This overview suggests that laser therapy is a safe and promising alternative to treat recurrent aphthous stomatitis, since it promotes wound healing and pain relief.

Effects of turmeric and curcumin on oral mucositis: A systematic review.

The aim of this study was to evaluate the effects of turmeric and curcumin in the management of oral mucositis in cancer patients undergoing chemo and/or radiotherapy. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The search was performed in the following database: Cochrane Library, LILACS, LIVIVO, PubMed, Scopus, and Web of Science. A gray literature search was undertaken using Google Scholar, Open Grey, and ProQuest. The methodology of included studies was evaluated by the Meta-Analysis of Statistics Assessment and Review Instrument. After a two-step selection process, four randomized and one nonrandomized clinical trials were included in the analysis. Two studies were categorized as low and three as moderate risk of bias. Turmeric/curcumin was applied topically as a gel or as a mouthwash. Patients treated with turmeric/curcumin experienced reduced grade of mucositis, pain, erythema intensity, and ulcerative area. Current evidence suggests that topical application of turmeric or curcumin is effective in controlling signs and symptoms of oral mucositis. Thus, further investigation is required to confirm the promising effect of turmeric and curcumin in oral inflammatory lesions.

Biomarkers in the assessment of oral mucositis in head and neck cancer patients: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to evaluate the capability of biomarkers to predict the risk of oral mucositis in head and neck cancer patients, as well as to assess the correlation between these biomarkers and the severity of mucositis. METHODS: The search was performed at LILACS, PubMed, Science Direct, Scopus, and Web of Science. A search of the gray literature was performed on Google Scholar, OpenGrey, and ProQuest. The methodological quality of the included studies was assessed using the Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) tool, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: After a two-step selection process, 26 studies met the eligibility criteria. In total, 27 biomarkers were evaluated, and the most frequent were the epidermal growth factor (EGF), C-reactive protein (CRP), genetic polymorphisms, tumor necrosis factor alpha (TNF-α), and erythrocyte sedimentation rate (ESR). The meta-analysis showed an expression of polymorphisms in XRCC1 (32.66%), XRCC3 (31.00%), and RAD51 (39.16%) genes, as well as an expression of protein biomarkers (39.57%), in patients with an increased risk of developing oral mucositis. CONCLUSIONS: Dosing biomarkers before starting radiation therapy may be a promising method to predict the risk of developing mucositis and allow radiosensitive patients to have a customized treatment. Although there is currently limited evidence to confirm the putative implementation of serum and salivary biomarkers to assess the correlation between them and the severity of mucositis, this current review provides new research directions.

Differences among oral carcinomas arising de novo from those associated with oral potentially malignant disorders: a systematic review and meta-analysis.

OBJECTIVE: To analyze the frequency of sequential oral squamous cell carcinomas (s-OSCC), preceded by oral potentially malignant disorders, and OSCC de novo (OSCC-dn) and explore differences in their clinicopathologic presentations. STUDY DESIGN: A structured electronic search strategy identified studies that analyzed frequency, clinical, biological, demographic, biomarkers, and prognostic features of s-OSCC and OSCC-dn according to PRISMA guidelines in PubMed, Scopus, Cochrane Library, and Google Scholar, up to January 31, 2023. Inclusion criteria were original English, Spanish, Portuguese, French, Italian, and German cross-sectional, cohort, and case-control studies. The quality of studies was assessed using the Agency for Research and Health Quality tool and the Newcastle-Ottawa Scale tool. RESULTS: The final selection included 40 studies. OSCC-dn and s-OSCC represent, respectively, 71% and 29% of cases of OSCC (P = .00), showing a higher percentage of T1 or of T1+T2 in s-OSCC (P < .0001). The association meta-analysis showed OSCC-dn with a significant association. The meta-analysis showed that s-OSCC was significantly associated with smaller tumor size, absence of distant metastases, relapses, male sex, and tumor sites different from tongue; and OSCC-dn was associated with more advanced tumor size, more regional and distant metastases, more advanced stages, and worse survival. CONCLUSIONS: S-OSCC was less frequent than expected. OSCC-dn seems to have specific clinical, biological, and prognostic features. Future perspectives on oral cancer prevention should address novel approaches and alternatives to screening, such as urgent referral of OSCC-dn.

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.

Peptidomics Strategies to Evaluate Cancer Diagnosis, Prognosis, and Treatment.

Peptides have potential bioactive functions, and the peptidomics landscape has been broadly investigated for various diseases, including cancer. In this chapter, we reviewed the past four years of literature available and selected 16 peer-reviewed publications exploring peptidomics in diagnosis, prognosis, and treatment in cancer research. We highlighted their main aims, mass spectrometry-based peptidomics, multi-omics, data-driven and in silico strategies, functional assays, and clinical applications. Moreover, we underscored several levels of difficulties in translating the peptidomics findings to clinical practice, aiming to learn with the accumulated knowledge and guide upcoming studies. Finally, this review reinforces the peptidomics robustness in discovering potential candidates for monitoring the several stages of cancer disease and therapeutic treatment, leveraging the management of cancer patients in the future.

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.

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.