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.

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.

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.

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.

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.

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.

A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia.

The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04-0.40), 0.44 (95% CI: 0.24-0.81), and 0.18 (95% CI: 0.04-0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.

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.

Global frequency and epidemiological profile of electronic cigarette users: a systematic review.

OBJECTIVE: Electronic cigarette (e-cigarette) use is growing significantly worldwide, especially among young people. This product has been associated with renormalizing smoking and hindering quit attempts in smokers. Moreover, among nonsmokers, it can lead to subsequent cigarette smoking and nicotine dependence. The present study aimed to assess the epidemiological profile of e-cigarette users worldwide. STUDY DESIGN: A systematic review was performed using 3 main electronic databases (Medline/PubMed, SCOPUS, and EMBASE). Studies were independently assessed by 2 reviewers based on established eligibility criteria. The risk of bias was assessed using the MAStARI critical appraisal instrument. RESULTS: From 4,496 records, 43 were included. Among the 1,238,392 participants, 132,786 (10.72%) were e-cigarette users. The age range with the highest percentage of e-cigarette users was 18-24 years old, with 40,989 (30.86%) males, 34,875 (26.26%) females, and 33.6% being current cigarette smokers. The highest prevalence of users was 52.88% in Croatia and 49.62% in New Zealand. Other possible correlations were observed with e-cigarette use, such as a high level of education. CONCLUSION: Overall, e-cigarette users tended to be male young adults with a higher level of education. The highest prevalence of use was found in Croatia. This systematic review provides valuable information to improve the development of appropriate intervention strategies targeting e-cigarette users for more accurate anti-smoking actions.

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.

Single nucleotide polymorphisms to predict acute radiation dermatitis in breast cancer patients: A systematic review and meta-analysis.

PURPOSE: To identify Single Nucleotide Polymorphisms (SNPs) that can predict acute radiation dermatitis (RD) in breast cancer patients (BC), and the association between SNPs and RD severity. METHODS: We performed the search in seven databases and the gray literature, and a meta-analysis to assess SNPs in patients with RD and to evaluate the association between SNPs and severe RD. RESULTS: We included sixteen single-arm cohort studies with 4742 BC. The most prevalent SNPs were the TGFß1 rs1800469 (41%), and the GSTA1 rs3957356 (36%). Seven genotypes were associated with severe RD (PTTG1 rs3811999-CC; PTTG1 rs2961950-AA; MAD2L2 rs2294638-GG; MAT1A rs2282367-GG; GSTA1 rs3957356-CT; CD44 rs8193-CT; SH3GL1 rs243336-GC) and five SNPs were associated with lower RD (PTTG1 rs2961952-GG; CD44 rs8193-CC; PTTG1 rs3811999-CT; MAT1A rs2282367-GA; OGG1 rs2075747-AA). CONCLUSIONS: The genotyping of SNPs more prevalent may be a strategy for predicting RD in BC, and some genotypes (GSTA1 rs3957356-CT; MAT1A rs2282367-GG) are associated with severe RD.

Preservation of immunoexpression of type I collagen, BSP and BMP4 in the dentin-pulp complex of head and neck cancer patients after radiotherapy.

This study tested the hypothesis that head and neck radiotherapy (HNRT) impacts the immunoexpression of type I collagen, bone sialoprotein (BSP) and bone morphogenetic protein 4 (BMP4), thereby leading to micromorphological changes in the dentin-pulp complex (DPC), and promoting the onset and progression of radiation caries (RC). Twenty-two demineralized sections of carious teeth (a group of 11 irradiated teeth and a control group of 11 non-irradiated teeth) extracted from 19 head and neck cancer patients were analyzed by conventional optical microscopy and immunohistochemistry to investigate the micromorphology (cellular layer hierarchy, blood vessels, odontoblasts, fibroblasts, extracellular matrix, calcification, necrosis, reactionary dentin formation, and chronic inflammation), and the patterns of staining/immunolocalization of type I collagen, BSP and BMP4 in the dental pulp of irradiated and control samples. No significant differences attributable to the direct impact of radiotherapy were detected in DPC micromorphology between the groups. In addition, the patterns of immunohistochemical staining and immunolocalization of the proteins studied did not differ between the irradiated and the control samples for type I collagen, BSP or BMP4. This study rejected the hypothesis that HNRT directly damages dentition by changing the organic components and the microstructure of the DPC, ultimately leading to RC.

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.