Impact of photobiomodulation for prevention of oral mucositis on the quality of life of patients with head and neck cancer: a systematic review.

The aim of this study was to perform a systematic review to evaluate the impact of photobiomodulation therapy (PBMT) for the prevention of oral mucositis (OM) on the quality of life (QoL) of patients with head and neck cancer (HNC) undergoing radiation therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy was performed in five electronic databases (Cochrane, Embase, PubMed, Scopus, and Web of Science). The included studies assessed the QoL of patients undergoing radiation therapy (RT) for HNC and undergoing PBMT for the management of OM. Seven articles met the eligibility criteria. Data extraction was performed in the selected studies including the PBMT parameters (active medium, application procedure, wavelength, fluence, power, irradiance, irradiation time, spot size, energy per point, schedule of irradiation, and total energy). The included studies were qualitatively analyzed, and descriptive analyses were performed. Also, summary results were evaluated for group comparison analysis. All included studies confirmed a decrease in the QoL of the patients that developed OM throughout the RT progress when compared to baseline. Of the informed cases, most of the patients who received PBMT showed grades 1 and 2 OM, while the control group showed more individuals with severe forms of OM (grades 3 and 4). In this sense, patients submitted to PBMT reported better QoL at the end of the treatment compared with the control group. PBMT used for the management of OM preserves the QoL of patients with head and neck cancer.

Virtual learning object about oral ulcerative lesions: controlled educational intervention study.

The aim of this study was to develop a virtual learning object (VLO) to teach undergraduate dental students about the diagnostic and therapeutic approaches to oral ulcerative lesions. The VLO was developed with information on the diagnostic process, lesion classification, and clinical-surgical management of oral ulcerative lesions. The VLO content was initially validated by a group of specialists. Learning was evaluated in a sample of 58 undergraduate dental students, divided into control group (conventional theoretical class, n = 29) and intervention group (interaction with VLO, n = 29). All students answered a pre-test and post-test questionnaire. The VLO group also answered a specific questionnaire on the evaluation of the VLO. Both quantitative and qualitative descriptive analyses were performed. The validation showed that professors and students considered the VLO adequate. The use of the VLO was recommended by 100% of professors and 86.6% of students. In the intervention group, the results showed a significantly higher number of correct answers in the post-test (p < 0.01). In conclusion, the VLO proved to be a useful tool for teaching oral medicine, contributing significantly to the knowledge of ulcerated lesions in the mouth.

Ewing's sarcoma of the head and neck: A systematic review.

OBJECTIVE: The aim of the present study was to conduct a systematic review of head and neck Ewing sarcoma (ES) concerning patients' demographic and clinical features, histopathological findings, treatment, follow-up, and survival rate. MATERIALS AND METHODS: An electronic search was undertaken in four databases. Articles describing case reports or case series were included. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. RESULTS: The search yielded 186 studies describing 227 ES cases. The mean age was 22.7 years, and males were slightly more affected. Interestingly, more than half the cases were diagnosed up to 20 years. The respiratory tract was the most reported site, followed by the jawbones. Clinically, symptomatic swelling or nodules were described, with a mean duration of 4 months. Management involved multimodal treatment regimens. Local recurrence, lymph node and distant metastasis were observed in 10.7%, 12.6%, and 20.3% of cases, respectively. Statistical analysis revealed that older patients with distant metastasis had a lower overall survival rate (p < 0.05). CONCLUSION: This study provides an overall view of head and neck ES that can assist oral and maxillofacial pathologists with the diagnosis and extend the knowledge of surgeons and oncologists about this condition.

Repurposing NFκB and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas.

Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) leading to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the population of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concentrations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells.

Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study.

The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Foreign body reactions related to orofacial esthetic fillers: A systematic review.

The aim of this study was to systematically review the clinicopathological data regarding foreign body reactions (FBR) related to esthetic procedures in the orofacial region. Electronic searches were performed in six databases and in gray literature using PEO acronym for the review question. Case series and case reports describing FBR related to esthetic procedures in the orofacial region were included. The JBI Critical Appraisal Checklist-University of Adelaide tool was used for measuring the risk of bias. Eighty-six studies reporting 139 cases of FBR were identified. The mean age at diagnosis was 54.12 years (14-85 years), with most of the cases reported in America, North America (n = 42/30.70%) and Latin America (n = 33/23.60%), mainly occurring in women (n = 131/94.40%). Asymptomatic (n = 60/43.40%) nodules (n = 71/50.60%) were the main clinical characteristics. The lower lip represented the most affected anatomical location (n = 28/22.20%), followed by the upper lip (n = 27/21.60%). Surgical removal was the treatment of choice (n = 53/35.70%). Twelve different dermal fillers were reported in the study, and the microscopic characteristics of the cases varied according to the material used. The results based on case series and case reports showed that nodule and swelling were the main clinical characteristics of FBR related to orofacial esthetic fillers. The histological characteristics depended on the type of the filler material used.

Drug-based therapy for advanced adenoid cystic carcinoma: Current landscape and challenges based on an overview of registered clinical trials.

Adenoid cystic carcinoma (ACC) has a significant patient-population in need of effective systemic therapy, as no drug is currently approved by the FDA for its management. We critically reviewed ACC-clinical trials (CT) registered on the ClinicalTrials.gov website using "ACC" under condition or disease. Trials specifically designed to test a drug-based therapy for ACC (n = 33) were analyzed with most being one-arm phase II trials enrolling advanced, recurrent/metastatic, incurable ACC cases. Site restriction, maximum ECOG status, and period of disease progression varied as inclusion criteria. Small-molecule inhibitors were those most commonly investigated with Apatinib, Axitinib and Lenvatinib showing the best results in association with rigid enrollment criteria. The overall median time to progression remains modest and more efforts are urgently needed in this field. CTs designed to test drugs that act on key pathways associated with ACC aggressiveness are being conducted and represent a promising pathway if efficacy is proved.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Oral and maxillofacial tuberculosis: A systematic review.

OBJECTIVES: This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow-up data on the occurrence of oral and maxillofacial tuberculosis (OMTB). METHODS: Electronic searches without publication date restrictions were undertaken in four databases. Case reports and case series describing the occurrence of OMTB were included. Critical evaluation of studies was done using the Joanna Briggs Institute - University of Adelaide tool for case reports or case series. RESULTS: A total of 217 studies were included in the qualitative synthesis, for a total of 301 cases of OMTB. Of these patients, 192 (63.7%) were male, with an average age of 39.6 ± 19.8 (15 months to 81 years). The tongue (n = 80/26.6%) represented the most common affected site, followed by the mandible (n = 43/14.3%). The clinical presentation consisted mainly of a painful ulcerated lesion (n = 156/56.5%). Histopathological analysis showed a granulomatous inflammation in most cases (n = 156/63.1%). The main diagnostic methods used were sputum test (n = 53/26.8%), culture (n = 49/24.7%) and purified protein derivative (PPD), or Mantoux test (n = 49/24.7%). Antituberculosis therapy was used in 244 cases (100.0%) and 5.2% of patients died. CONCLUSIONS: This systematic review provided clinical, demographic data and information about diagnostic methods of OMTB lesions and served as an important guide to assist health professionals in the early diagnosis of these lesions.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Association between perceived self-confidence and abilities to distinguish oral mucosal lesions amongst dental students.

INTRODUCTION: Dentists usually refer to difficulties in performing the diagnosis of oral mucosal lesions. This may be attributed to limited access to theoretical lectures and practical training on this subject along the graduation course. The primary aim of this cross-sectional study was to verify if there is an association between the perception of time dedicated to lectures/training and oral diagnosis abilities in oral medicine. The secondary aim was to evaluate the association between self--confidence to perform oral mucosal lesions diagnosis and performance in a diagnostic abilities test. MATERIALS AND METHODS: The sample comprised 36 final-year dental students of a South-Brazilian dental school. The participants answered a questionnaire on their perception of time dedicated to lectures on oral medicine along the course (sufficient or insufficient) and their self-confidence to diagnose oral mucosal lesions or oral cancer (yes or not). The students were also submitted to a diagnostic abilities test based on 30 clinical photos of oral lesions, which should be classified as benign, potentially malignant or malignant. Moreover, the participants had to inform their clinical impression for each case. Finally, the participants informed their decision making for the case (refer the patient to a specialist or not). RESULTS: Students with higher self-confidence showed a higher percentage of correct answers on classification of the nature of lesions (81.1% vs. 68.5%, p = .03, teste t de Student) and on their clinical impression (66.3% vs. 41.7%, p < .01, Student's t-test). The perception of time dedicated to theoretical lectures on oral medicine as sufficient did not influence the students' diagnostic abilities (p > .05, Student's t-test) CONCLUSION: It may be concluded that self-confidence to diagnose oral lesions is associated with dental students' diagnostic abilities.

Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study

Abstract The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Virtual learning object about oral ulcerative lesions: controlled educational intervention study

Abstract The aim of this study was to develop a virtual learning object (VLO) to teach undergraduate dental students about the diagnostic and therapeutic approaches to oral ulcerative lesions. The VLO was developed with information on the diagnostic process, lesion classification, and clinical-surgical management of oral ulcerative lesions. The VLO content was initially validated by a group of specialists. Learning was evaluated in a sample of 58 undergraduate dental students, divided into control group (conventional theoretical class, n = 29) and intervention group (interaction with VLO, n = 29). All students answered a pre-test and post-test questionnaire. The VLO group also answered a specific questionnaire on the evaluation of the VLO. Both quantitative and qualitative descriptive analyses were performed. The validation showed that professors and students considered the VLO adequate. The use of the VLO was recommended by 100% of professors and 86.6% of students. In the intervention group, the results showed a significantly higher number of correct answers in the post-test (p < 0.01). In conclusion, the VLO proved to be a useful tool for teaching oral medicine, contributing significantly to the knowledge of ulcerated lesions in the mouth.

Oral squamous cell carcinoma cancer stem cells have different drug sensitive to pharmacological NFκB and histone deacetylation inhibition.

Despite many progresses in the development of new systemic therapies for oral squamous cell carcinoma (OSCC), the five-year survival rate of OSCC is low. The traditional chemotherapies approach (cisplatin - CDDP) shows some limitations like drug toxicity, limited efficacy, and drug resistance. Promising studies suggested OSCC cancer stem cells (CSC) presented resistance to CDDP. We have previously studied many targets, and we extensively showed the efficacy of the NFκB signaling and the role of histones acetylation, on different malignant tumors, including adenoid cystic carcinoma and mucoepidermoid carcinoma, but until then the effects of the NFkB inhibitor and histone deacetylase (HDAC) inhibitor on the biology of OSCC were not evaluated. Here we assessed the pharmacological inhibitor of NFκB emetine and HDAC inhibitor SAHA on the behavior of CSC derived from OSCC. Our data suggested that CDDP administration resulted in reduced viability of bulk OSCC cells and increased CSC. A single and isolated shot of emetine and SAHA were able to disrupt CSC by inhibiting the NFκB pathway and increasing the histone acetylation levels, respectively. Further, the combined administration of emetine and SAHA presented the same CSC disruption as seen in emetine alone.

Risk factors for jaw osteoradionecrosis: a case control study.

There are divergences among studies regarding features associated to increased risk of osteoradionecrosis (ORN). Our objective was to identify factors that predispose to the development of ORN of the jaw. This was a retrospective, hospital-based, case-control study involving patients with head and neck cancer who had been treated with ≥ 60 Gy external radiotherapy (RT) to the jaw. A total of 19 cases of ORN and 43 controls were included. The patients' demographic data, tumor type, staging, treatment and outcome information, and pre-treatment oral status were collected. Univariate analysis showed that the oral cavity/oropharynx sites were associated with 9.77-fold increased risk of ORN development compared to other sites (p = 0.005). Being an active smoker was associated with 3.95-fold increased risk of ORN development (p = 0.01). A tendency towards increased risk of ORN was observed particularly when tooth extraction occurred after RT (odds ratio (OR): 3.04; p = 0.08). Multivariable analysis showed that tumor site was the only significant risk factor (OR: 21.03, p = 0.01). The oral and oropharyngeal primary site is an important risk factor for ORN. Dental extraction, which did not occur in 28% of the sample, was not an essential event for ORN development.

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.

Effects of different protocols of defocused high-power laser on the viability and migration of myoblasts-a comparative in vitro study.

The aim of the present study was to analyze for the first time the effect of photobiomodulation therapy (PBMT) using defocused high-power laser (DHPL) in myoblast cell line C2C12 viability and migration and compare them with low-power laser therapy. Cells were divided into 9 groups: Sham irradiation 10% fetal bovine serum (FBS); Sham irradiation 5%FBS; low-power laser 0.1 W; DHPL 810 1 W; DHPL 810 2 W; DHPL 980 1 W; DHPL 980 2 W; DHPL dual 1 W; DHPL dual 2 W. To simulate stress conditions, all groups exposed to irradiation were maintained in DMEM 5% FBS. The impact of therapies on cell viability was assessed through sulforhodamine B assay and on cells migration through scratch assays and time-lapse. Myoblast viability was not modified by PBMT protocols. All PBMT protocols were able to accelerate the scratch closure after 6 and 18 h of the first irradiation (p < 0.001). Also, an increase in migration speed, with a more pronounced effect of DHPL laser using dual-wavelength protocol with 2 W was observed (p < 0.001). In conclusion, the diverse PBMT protocols used in this study accelerated the C2C12 myoblasts migration, with 2-W dual-wavelength outstanding as the most effective protocol tested. Benefits from treating muscle injuries with PBMT appear to be related to its capacity to induce cell migration without notable impact on cell viability.

Distance learning course improves primary care dentists' diagnosis and self-efficacy in the management of oral lesions.

Oral cancer represents a public health issue because of its high mortality rate, resulting mainly from diagnostic delays. Insufficient training in oral diagnosis is usually perceived by dentists. Distance learning could be used as an auxiliary tool to bridge that gap. This study evaluated the impact of a distance learning course on oral mucosal lesion diagnosis offered to public healthcare dentists. Participants of an online course answered a pretest/posttest comprising clinical images of 30 clinical cases. Participants were questioned about the diagnosis and informed their decision on the cases (referring the cases to a specialist or managing them themselves), as a parameter of perceived self-efficacy. A total of 442 dentists enrolled in the course. Their pass rate was 97%. Classification of the nature of the lesions, diagnostic hypotheses, sensitivity, and specificity improved by 13.4%, 10.0%, 13.4%, and 6.6%, respectively (p<0.01, Wilcoxon test). Regarding management, there was a 16.6% reduction in the intention to refer cases, while confidence in the diagnosis of benign lesions increased by 40%. A distance learning course may be useful in continuing education actions for primary care dentists, improving their diagnostic abilities and encouraging them in the management of oral lesions. Moreover, this strategy could contribute to disseminating knowledge to remote regions, particularly among primary health care professionals.

4-nitroquinoline-1-oxide (4NQO) induced oral carcinogenesis: A systematic literature review.

OBJECTIVE: Based on a critical review of published studies, we aimed to develop a good practice guide for using 4-nitroquinoline-1-oxide (4NQO) as an inducer of oral carcinogenesis in Wistar rats. DESIGN: A systematic search was performed on Medline Ovid, PubMed, Embase, Web of Science, and Scopus databases. The SYRCLE's risk of bias tool was used to assess the quality of the studies. RESULTS: Thirty-five articles met the selection criteria; 22 (62.9%) of them administered 4NQO systemically in drinking water, with a mean concentration of 30.2 ppm (SD±15.9) and during a mean period of 20.8 (SD±7.8) weeks. The other 13 (37.1%) studies performed topical applications of 4NQO painting the oral mucosa of the animals three times a week (100%) with a mean period of administration of 16.8 (SD±7.0) weeks. Different 4NQO concentrations used for other periods achieved significant tumor development. Most studies didn't perform quantitative clinical analysis, and the histopathological diagnosis/grading criteria varied considerably. CONCLUSIONS: A poor description of solution care, adverse effects, and the number of losses were observed, and the reporting of these features needs to be improved. Suggestions to guide the development of future research are provided.

Potentially carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Little is known about the extent to which hydrogen peroxide as used for tooth bleaching could be carcinogenic to the oral mucosa. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether hydrogen peroxide as used for tooth bleaching has carcinogenic effects on the oral mucosa. MATERIAL AND METHODS: PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Studies evaluating different outcomes potentially related to the carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa were included. Risk of bias was assessed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I), or Risk of Bias 2 (RoB 2) tools. The strength of the evidence was assessed by using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. The quantitative analysis was performed with means, standard deviations, and 95% confidence intervals (CIs). Heterogeneity was analyzed by using I-squared statistics. RESULTS: Thirteen articles comprising 5 animal and 8 clinical studies met the inclusion criteria. Three of the 5 animal studies associated the bleaching agents with a carcinogen and demonstrated an enhancement of the carcinogenic effect, but probably with the bleaching agent acting only as a promoter. Five clinical studies concluded that the bleaching agents did not cause mutagenic stress on the oral mucosa by using the micronucleus test. The meta-analysis demonstrated that the frequency of micronuclei did not differ significantly between baseline and 30 days after bleaching (mean difference: 0.48; 95% CI, -1.49, 2.46; P=.63). CONCLUSIONS: This systematic review indicated that hydrogen peroxide does not appear to have carcinogenic effects on the oral mucosa.