Correlation of Clinical and Histopathological Features of Salivary Pleomorphic Adenoma.

Statement of the Problem: Salivary gland tumors represent about 3% of the head and neck tumors. Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Purpose: This study was conducted to investigate and describe some clinical and histopathological aspects of salivary pleomorphic adenomas with special reference to the epithelial and mesenchymal components. Materials and Method: In this retrospective study, one hundred tissue samples diagnosed as PA were sourced from archival tissue blocks between 2009 and 2019 in this retrospective study. Some clinical and demographic features, including age, sex, tumor size, and tumor location were recorded. This study included only samples taken by excisional biopsy. Then, the samples were histologically classified into three subtypes according to the proportion of epithelial and stromal components. The demographic and clinicopathological variables were statistically analyzed using Chi-square test or Fisher's exact test, considering a significance level of 5% (p< .05). Results: In the present study, most cases (61%) were found in females, representing a female-male ratio of 1.6:1. The peak incidence was seen in the 4th and 5th decades of life. In 87% of cases, PA occurred in major salivary glands. There was a significant difference between the age of the patient and squamous metaplasia (p= 0.036). There was also a significant difference between the size of tumor and the amount of myxoid stroma (p= 0.021). Extensive myxoid stroma was mostly seen in tumors larger than 3.37cm (p= 0.001). In addition, there was a statistically significant difference between capsular invasion and the development of squamous metaplasia (p= 0.001). Conclusion: In this study, there was a significant correlation between the gland type and capsular features and between the size of tumor and rate of squamous metaplasia. A detailed clinical and histopathological analysis of PAs may provide a better insight to the pathophysiology of the lesion, tumor cell differentiation, and prognostic factors.

Immunohistochemical Localization of Endothelin- 1 and Endothelin A Receptor in Human Primary Tooth Enamel Organ.

Statement of the Problem: Enamel organ (EO) is an ectodermal derived structure, which is involved in the different aspects of tooth development. Tooth development shares the same regulatory molecules and genes expressed in other developing organs. Endothelin- 1 (ET-1) and Endothelin A receptor (ETAR), (ET-1/ETAR) axis, are involved in differentiation of embryonic stem cells and organ development. Purpose: The present study aimed to investigate the ET-1 and ETAR expression profiles during the development of human primary tooth EO with the relatively large sample size. Materials and Method: In this experimental study, 33 human fetuses aged from 13 to 23 weeks (3 samples from each fetal age) were collected. The samples were divided into three age groups (<16 weeks, <19 weeks, ≥19 weeks) and cut for hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining. A two-way ANOVA test was conducted to examine the expression levels of ET-1 and ETAR in different layers of human primary tooth EO. The statistical significance was assumed at p ≤ 0.05. Results: There were statistically significant differences between the expression levels of ET-1/ETAR axis in the four-layered human primary tooth EO in different fetal ages (13-23 weeks). Besides, there were significant differences between the expression levels of ET-1/ETAR axis in all layers of human primary enamel organ and types of teeth. Conclusion: Due to the profile of expression of ET-1/ETAR axis, it can be concluded that this axis contributes to the differentiation of all human primary EO layers and secretion of enamel. ET-1/ETAR axis is one of the signaling molecules, which may have crucial roles in tooth development.

Web design software to record the characteristics of children with cleft palate/cleft lip.

Background: Cleft lip (CL) and cleft palate (CP) are among the most common birth defects in the craniofacial region affected by various environmental and genetic factors. The prevalence of these abnormalities varies in races and countries. Therefore, it is a necessity to design a website to register newborns with CL ± CP in Iran. This study aimed to design a website to record the characteristics of children with CL ± CP. Materials and Methods: First, a website was designed to register the characteristics of children with CL ± CP. To evaluate the accuracy of the website, the characteristics of all children (n = 31) with CL ± CP were recorded and analyzed. Results: Due to the capability of the website to print and create reports in Excel format, the data of registered patients were analyzed. Conclusion: As CL ± CP are very common defects around the world including Iran, it is necessary to design a website to record all information about these children in Iran. Hope this website helps the public health authorities to improve program effectiveness to treat these children.

Immune Responses in SARS-CoV-2, SARS-CoV, and MERS-CoV Infections: A Comparative Review.

Coronavirus, discovered in the 1960s, is able to infect human hosts and causes mild to serious respiratory problems. In the last two decades, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recognized. It has long been demonstrated that MERS-CoV binds to dipeptidyl peptidase 4 and SARS-CoV binds to angiotensin-converting enzyme 2. A "cytokine storm" is the main pathophysiology of aforementioned viruses. Infiltration of neutrophils at the site of the infection is a risk factor for the development of acute respiratory distress syndrome and death. The new coronavirus, SARS-CoV-2, has infected more people than SARS-Cov and MERS-CoV as it can easily be transmitted from person to person. Epidemiological studies indicate that majority of individuals are asymptomatic; therefore, an effective and an efficient tool is required for rapid testing. Identification of various cytokine and inflammatory factor expression levels can help in outcome prediction. In this study we reviewed immune responses in SARS-CoV, Mers-CoV, and SARS-COV-2 infections and the role of inflammatory cells.

Prophylactic effect of topical (slow-release) and systemic curcumin nano-niosome antioxidant on oral cancer in rat.

BACKGROUND: Oral malignancies have a significant effect on the quality of life among the affected patients. Curcumin is an antioxidant with a low bioavailability in the target tissue. Niosomes are carriers of increasing the therapeutic effects of drugs and reducing their side effects. This study aimed to determine the effective dose of curcumin niosome in the culture and then to compare its prophylactic effect in the form of mouthwash with that of its injectable form on oral cancer in rats. METHODS: This was an in-vitro and in-vivo study. Firstly, KB oral cancer cells and human umbilical vein endothelial cells (HUVEC) were treated in separate groups with free curcumin, curcumin-loaded niosomes, and the unloaded niosomes at four doses of 4, 8, 16, and 32 µg. The study rats were then divided into the following four groups: 1) no intervention, 2) only carcinogenic substance, 3) carcinogenic substance with curcumin-loaded niosome injection, and 4) carcinogenic substance with a mouthwash containing niosome. RESULTS: At the cellular level, a dose of 16 µg after 24 h was selected as an effective dose. In the animal phase, the use of injectable curcumin niosome was observed to significantly prevent the development of severe forms of dysplasia. CONCLUSIONS: In this in-vitro and in-vivo study, curcumin-loaded niosome was effective in preventing the development of severe forms of dysplasia and the inhibition of the growth of cancer cells.

Periodontitis and oral cancer - current concepts of the etiopathogenesis.

Gingival tissues are attacked by oral pathogens which can induce inflammatory reactions. The immune-inflammatory responses play essential roles in the patient susceptibility to periodontal diseases. There is a wealth of evidence indicating a link between chronic inflammation and risk of malignant transformation of the affected oral epithelium. Periodontitis is associated with an increased risk of developing chronic systemic conditions including autoimmune diseases and different types of cancers. Besides, some risk factors such as smoking, alcohol consumption and human papilloma virus have been found to be associated with both periodontitis and oral cancer. This review article aimed to study the current concepts in pathogenesis of chronic periodontitis and oral cancer by reviewing the related articles.

New Insights into Oral Cancer-Risk Factors and Prevention: A Review of Literature.

The oral cancer constitutes 48% of head and neck cancer cases. Ninety percent of oral cancer cases are histologically diagnosed as oral squamous cell carcinomas (OSCCs). Despite new management strategies, the 5-year survival rate of oral cancer is still below 50% in most countries. Head and neck cancers are heterogeneous tumors, and this characteristic of them provides a challenge to treatment plan. Due to the poor outcomes in oral cancer, prevention is a necessity. In this review, a relevant English Literature search in PubMed, ScienceDirect, and Google Scholar from 2000 to mid-2018 was performed. All published articles related to oral cancer and its prevention were included. The risk factors of oral cancer and strategies of oral cancer prevention will be discussed.

Emerging insights into the biology of metastasis: A review article.

Metastasis means the dissemination of the cancer cells from one organ to another which is not directly connected to the primary site. Metastasis has a crucial role in the prognosis of cancer patients. A few theories, different types of cell and several molecular pathways have been proposed to explain the mechanism of metastasis. In this work, the related articles in the limited period of time, 2000-mid -2018 were reviewed, through search in PubMed, Google Scholar and Scopus database. The articles published in the last two decades related to the biology of cancer metastasis were selected and the most important factors were discussed. Metastasis is critical factor to predict survival in patients with advanced cancer and prognosis determines the treatment plan. Many different cell types and various signaling pathways control the metastatic process. Metastasis is a multistep process. Many signaling pathways and molecules are involved in metastasis. Increasing knowledge about the mechanism of metastasis can help in finding the promising targets of cancer therapy.

Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers.

BACKGROUND: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma. OBJECTIVE: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. METHODS: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis. RESULTS: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells. CONCLUSION: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.

Expression of vimentin and CD44 in mucoepidermoid carcinoma: A role in tumor growth.

BACKGROUND: Cancer stem cells (CSCs) may participate in angiogenesis by lining the wall of tumor vessels. AIM: The current study aimed to present the role of vimentin and CD44 in inducing vasculogenic mimicry (VM) and epithelial-mesenchymal transition (EMT) in different grades of mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: A total of 63 MEC samples were collected from the archive of Department of Pathology of Taleghani Educational Hospital, Tehran, Iran. Vimentin and CD44/periodic acid-Schiff double staining was performed. STATISTICAL ANALYSIS: Chi-square test was used to examine the differences with categorical variables. Significance level was set at 0.05. Pearson's correlation coefficient was used to assess the colocalization of the markers. RESULTS: There were statistically significant differences between tumor grade and the expression levels of vimentin and CD44 (P = 0.000). CONCLUSION: Our results may disclose a definite relationship between microvessl density (MVD), VM, EMT, and CSCs in MEC samples. Thus, it is reasonable to suggest that CSCs are related to angiogenesis and VM.

The Expression and Functional Significance of Vascular Endothelial-Cadherin, CD44, and Vimentin in Oral Squamous Cell Carcinoma.

OBJECTIVES: Ninety percent of head and neck cancers are squamous cell carcinoma which develops in the oral cavity. Metastasis is the main causative factor for death in 90% of all cancer-related deaths and begins with the invasion of tumor cells through the walls of small blood vessels or lymph vessels. A growing body of evidence has shown that vasculogenic mimicry (VM) facilitates tumor growth and cancer metastasis. The current study aimed to present the role of vascular endothelial (VE)-cadherin, CD44, and vimentin in inducing VM and epithelial-mesenchymal transition (EMT) and to identify the cancer stem cell (CSC) niche in different grades of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: A total of 63 OSCC samples (21 samples each grade) were collected from the archive of Pathology Department of Besat educational hospital, Hamadan, Iran, from 2000 to 2015. VE-cadherin, CD44, and vimentin/periodic acid-Schiff (PAS) double-staining were used to validate VM. VM was identified by the detection of PAS-positive loops surrounded by tumor cells. Chi-square test was used to examine the differences between the variables. Significant level was set at 0.05. Pearson's correlation was used to assess the co-localization of the markers. RESULTS: There were statistically significant differences between tumor grade and the expression levels of VE-cadherin, CD44, and vimentin (P = 0.000). In addition, significant differences were found between tumor grade and microvessel density (P = 0.000) and between tumor grade and VM (P = 0.000). CONCLUSION: Our results may disclose a definite relationship between VE-cadherin, CD44 and vimentin expression levels, VM formation, EMT, CSCs, and microvessel count in OSCC samples. For this reason, it is suggested that VE-cadherin, CD44, and vimentin are related to angiogenesis and VM formation in OSCC, therefore, in tumor progression and metastasis. Recently, antitumor angiogenic therapies have been challenged. The presence of VM may explain the failure of antiangiogenic treatments.

BRCA1/2 Mutations in Salivary Pleomorphic Adenoma and Carcinoma-ex-Pleomorphic Adenoma.

OBJECTIVES: It is hypothesized that carcinoma-ex-pleomorphic adenoma (Ca-ex-PA) is malignant from the beginning or is a malignant transformation of a recurrent or a long-standing pleomorphic adenoma (PA). The accumulation of genetic instabilities is suggested to be the main reason for malignant transformation in PA. The aim of this study was to determine the prevalence of BRCA1/2 mutations in PA and Ca-ex-PA. MATERIALS AND METHODS: A total of ninety salivary gland tumors (45 Ca ex-PA and 45 PA) were selected. Immunohistochemistry was performed for all samples. Analyses were conducted through SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). Chi-square test was used to examine the differences between the variables. Significant level was set at 0.05. RESULTS: In general, 93.3% of PA samples showed positive staining for BRCA1 (in myoepithelial cells); however, BRCA2 positivity was found in 60% of samples (in myoepithelial cells). Among 45 samples of Ca-ex-PA, 93.3% of showed positivity for BRCA1 and 80% of samples showed positivity for BRCA2. Chi-square test found differences between PAs and Ca-ex-PAs regarding BRCA1/2 mutations in ductal cells and myoepithelial cells (P = 0.007, 0.000), respectively. CONCLUSIONS: The present study found a trend toward the presence of BRCA1/2 mutations in PA and Ca-ex-PA samples. Patients with BRCA1/2 mutation carriers are excellent cases for therapies, such as the poly (ADP) ribose polymerase inhibitor.

Orofacial Bacterial Infectious Diseases: An Update.

OBJECTIVES: Most of the oral infections with odontogenic origin are very common and can be treated by tooth extraction, endodontic therapy, or surgical treatment. Other infectious lesions are the manifestations of systemic diseases such as tuberculosis and syphilis. Skin and underlying subcutaneous tissue, fascia, or muscle is also involved with infectious diseases which range from superficial epidermal infections to very serious necrotizing fasciitis. MATERIALS AND METHODS: An extensive literature in PubMed, Google Scholar, and Scopus search was performed from 1980 to 2017. All related articles were analyzed. RESULTS: Most oral infections have odontogenic origin. Skin and the underlying subcutaneous tissue, fascia, or muscles are also involved with infectious diseases which range from superficial epidermal infections to very serious necrotizing fasciitis. CONCLUSIONS: These facts prove that the interaction between the oral cavity, face skin, and the other organs can risk the people's life. The establishment of a correct diagnosis and recognition of clinical findings are the crucial steps to support and improve professional orofacial health status.

Histologic Variants of Calcifying Odontogenic Cyst: A Study of 52 Cases.

AIM: This study aimed at evaluating histological features of 52 cases of calcifying odontogenic cyst (COC), which is an uncommon benign odontogenic lesion. The World Health Organization (WHO) classified COC as a neoplasm and used the term calcifying cystic odontogenic tumor (CCOT) for benign cystic type and the dentinogenic ghost cell tumor (DGCT) for the benign solid-type lesions. There is no agreement regarding COC classification. MATERIALS AND METHODS: A total of 52 cases of COC were selected and reviewed from the archive of the Pathology Department of Taleghani Educational Hospital, Tehran, Iran. To better understand the pathogenesis of COC, the cases were classified. RESULTS: There were 52 cases (31 males and 21 females). The lesion was found in all age groups, and patients' age from 8 to 61 years. Nineteen cases affected the maxilla, and 33 cases affected the mandible. Except two cases, all were intraosseous lesions. Radiographically, 30 cases showed a unilocular radiolucent area, and 22 cases showed a mixed radiolucent/ radiopaque region. Histopathologically, 43 cases were cystic type and 9 cases were neoplastic. CONCLUSION: There are two different histopathological entities. In view of these findings, it is very difficult to determine every lesion that has a cystic architecture is truly cystic or is a neoplastic one in nature. It is believed that the solid variants may be neoplastic. CLINICAL SIGNIFICANCE: A better understanding of the histological type of the lesion can provide a classification across patients. This can help in treatment planning to improve patient outcomes.

Metastasis to the Jawbones: A review of 453 cases.

The purpose of the present article was to review the characteristics of the jawbone metastases to analyze all variables. A relevant English Literature search in PubMed, Scopus, and Google Scholar was performed. All variables such as age, gender, primary and secondary tumor sites were analyzed. There were 453 metastatic cases. The male-to-female ratio was 1.2:1, and the mean age of the patients was 53.4 years. The lung was the most common primary site in men, and breast in women. The most common metastatic site was the mandible, and adenocarcinoma was the most frequent histological diagnosis. Metastases to the jaw bones occur in the advanced stages of a malignancy hence; a careful examination of patients with jaw bone lesions is strongly suggested. Dentists, as well as general physicians, should take into consideration the possible presence of jaw metastases in cases which present atypical symptoms, especially in patients with known malignant disease.

Expression of Vascular Endothelial-Cadherin in Mucoepidermoid Carcinoma: Role in Cancer Development.

OBJECTIVES: Mucoepidermoid carcinoma (MEC) accounts for 35% of all malignant salivary gland tumors. Previous investigations have shown that vasculogenic mimicry (VM) exists in many cancers which can be used as a prognostic factor of poor prognosis. Elevated expression level of vascular endothelial (VE)-cadherin has been implicated in cancer neovascularization, growth, and progression. The current study aimed to study the presence of VE-cadherin in VM channels and tumor cells in different grades of MEC. MATERIALS AND METHODS: A total of 63 MEC samples (21 samples in each grade) were collected from the archive of pathology department of Besat Educational Hospital, Hamadan, Iran, from 2002 to 2016. Hematoxylin and eosin staining was performed to confirm the previous diagnosis. The specimens were then processed for immunohistochemistry analysis. Then, periodic acid-Schiff staining was performed. Analyses were conducted through SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). Chi-square test was used to examine the differences between categorical variables. Significance level was set at 0.05. Pearson's correlation was used to assess the co-localization of the marker. RESULTS: A total of 63 samples (35 men; 55.6%, and 28 women; 44.4%) were used for immunohistochemical study. There were statistically significant differences between tumor grade and the expression levels of VE-cadherin (P = 0.000), between tumor grade and VM formation (P = 0.000), and also between tumor grade and microvessel density (MVD) (P = 0.000). Additionally, there was a strong positive correlation between tumor grade and VE-cadherin expression level (Pearson's r = 0.875, P < 0.000). CONCLUSIONS: Our results may disclose a definite relationship between VE-cadherin expression level, VM, epithelial-mesenchymal transition, cancer stem cells, and MVD in MEC samples. Thus, it is reasonable to suggest that VE-cadherin is related to angiogenesis and VM formation in MECs.

Metastasis to the oral soft tissues: A review of 412 cases.

The present review article analyzes the characteristics of metastases to the oral soft tissues from 1937 to 2015. An extensive literature search was performed. All variables such as age, gender, and primary and secondary tumor sites were analyzed. Metastases to the major salivary glands were not included in this review. In general, there were 412 metastatic lesions developed in the oral soft tissues. The male-to-female ratio was approximately 1.8:1. The mean age of the patients at diagnosis was 58. The lung was the most common primary site and the gingiva was the most common metastatic site. The greater part of the histological examination yielded adenocarcinoma. The diagnosis of a metastatic lesion in the oral cavity is a challenge to the clinicians due to the lack of pathognomonic signs and symptoms. Oral metastases usually occur in the advanced stages of cancers, and the interval between appearance and death is usually short. The oral soft tissue metastasis can be easily recognized compared to the metastasis of jawbones. Early detection of oral lesions is important in the case of being the first sign of a malignancy in other parts of body.

Dysplastic change rate in cases of oral lichen planus: A retrospective study of 112 cases in an Iranian population.

BACKGROUNDS: Lichen planus is a chronic systemic disease and oral mucosa is commonly involved. Oral lichen planus (OLP) most commonly affects middle-aged women. The prevalence of the disease ranges between 0.5% and 2.6% in the general population and the range of malignant transformation varies between 0% and 10%. OBJECTIVES: To assess the rate of malignant transformation of OLP samples. MATERIALS AND METHODS: This retrospective study was carried out on 112 medical records of patients with histological diagnosis of OLP who attended the Department of Pathology at the Educational Hospital from 2005 to 2012. H&E-stained slides were reviewed by two pathologists using strict clinical and histopathological diagnostic World Health Organization (WHO) criteria. Dysplastic changes were diagnosed and graded according to the latest WHO classification. RESULTS: Of the 112 cases diagnosed as OLP, there were 39 males and 73 females and the patients' ages ranged from 15 to 86 years (mean age 44.5 years). The erosive form with fifty cases was the most common clinical type and the papular type with one case was the least common clinical type. Regarding the site, the buccal mucosa was the most common site with 52 cases. Totally, dysplastic changes were found in 12 samples, among them five cases showed mild dysplasia and seven cases showed moderate dysplasia. One case developed oral squamous cell carcinoma after 3 years. CONCLUSION: OLP is considered as a premalignant condition by the WHO and several authors. Although the malignancy rate is not so high, to reduce morbidity and mortality from cancer arising on OLP lesions, a regular follow-up examination is recommended.

Distant metastasis from oral cancer: A review and molecular biologic aspects.

Oral squamous cell carcinoma (OSCC) has been estimated to be the sixth most common cancer worldwide. The distant metastasis plays a critical role in the management and prognosis in oral cancer patients. Regarding the distant metastasis from the oral cancer, the hypopharynx is the most common primary site, followed by the base of tongue and anterior tongue. The present review article analyzes the characteristics of the distant metastases from the oral cavity from 1937 to 2015.

miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review.

STATEMENT OF THE PROBLEM: Head and neck cancers include epithelial tumors arising in the oral cavity, pharynx, larynx, paranasal sinuses, and nasal cavity. Metastasis is a hallmark of cancer. MicroRNAs (miRNAs) are endogenous small non-coding RNAs involved in cell proliferation, development, differentiation and metastasis. It is believed that miRNA alterations correlate with initiation and progression of cancer cell proliferation or inhibition of tumorigenesis. Moreover, miRNAs have different roles in development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). Altered expression of miRNAs could be novel molecular biomarkers for the definite diagnosis of cancer, metastatic site, cancer stage, and its progression. PURPOSE: The purpose of this review was to provide a comprehensive literature review of the role of miRNAs in head and neck cancer metastasis. SEARCH STRATEGY: A relevant English literature search in PubMed, ScienceDirect, and Google Scholar was performed. The keywords 'miRNA', 'head and neck', and 'cancer' were searched in title and abstract of publications; limited from 1990 to 2015. The inclusion criterion was the role of miRNAs in cancer metastasis. The exclusion criterion was the other functions of miRNAs in cancers. Out of 15221 articles, the full texts of 442 articles were retrieved and only 133 articles met the inclusion criteria. CONCLUSION: Despite the advances in cancer treatment, the mortality rate of HNSCC is still high. The potential application of miRNAs for cancer therapy has been demonstrated in many studies; miRNAs function as either tumor suppressor or oncogene. The recognition of metastamir and their targets may lead to better understanding of HNSCC oncogenesis, and consequently, development of new therapeutic strategies which is a necessity in cancer treatment. Development of therapeutic agents based on miRNAs is a promising target.