Oral squamous cell carcinoma (OSCC) is the 16th most common cancer in the world with an annual prevalence of >377,000 cases, 70 % of which are men [1]. Although it does not include a high percentage of cancers, the chance of surviving patients is lower than the common breast and prostate cancers. SCC accounts for >90 % of oral cavity cancers that originate from the epithelium of the oral mucosa. As most of these lesions may not be diagnosed in early stages, almost 50 % of patients face treatment failure. Therefore, early diagnosis is as important as knowing risk factors [[2], [3], [4]]. Over the past few decades, despite the numerous advances in the field of surgery, radiotherapy and chemotherapy, the 5-year survival rate of oral cancer has not improved significantly. In the case of early detection, the survival rate is around 89 %, while in advanced stages, it drops to 39 % and the treatment at this stage is very debilitating and usually fatal [[5], [6], [7]].

OSCC is a multifactorial disease. Most of OSCCs arise from premalignant lesions. The most important premalignant lesion is leukoplakia, which has the possibility of turning into SCC due to the occurrence of dysplastic changes in the epithelium [2].

The gold standard for OSCC diagnosis is clinical examination with biopsy and histopathological examination. The most important and predictive factor that determines the survival rate is the stage of the tumor at diagnosis [8]. The TNM classification is a globally recognized method for staging oral cancers used by health care providers. The histopathological grading of SCC classifies the lesions in grades I to III or I to IV. Of course, gradually, the CAP method (College of American pathologists) grading system, which is based on clinical criteria and the relationship between histology and prognosis, replaces the traditional grading method [9].

Prognosis is defined as predicting the possible cause, duration and outcome of the disease based on general knowledge of the pathogenesis and the presence of risk factors. It predicts the course or outcome of a disease. DFS is defined as the time interval from disease treatment to tumor recurrence or death. Overall survival is defined as the time interval between disease diagnosis and death, regardless of disease recurrence [10].

The treatment of OSCC is based on the stage and condition of the patient. The essential treatment options for oral cancer consist of surgery, radiotherapy and chemotherapy or a combination of these methods. Resistance to treatment, recurrence and metastasis are the main cause of treatment failure in OSCC patients. Most of this phenomenon is attributed to the diverse structure of this tumor, which consists of heterogeneous lineages of cancer cells [11].

According to the model of cancer stem cells (CSCs), the stem cells located in the basal layer become malignant. A common method to isolate CSCs is to sort them based on the expression of cell surface markers [12,13]. CD44 is a cell surface adhesive molecule that is involved in intercellular junctions, migration, angiogenesis, tumor spread and metastasis. In order to investigate the increase of patients' resistance to radiotherapy and chemotherapy, CSCs have been given more attention in cancer-related research [14].

Overexpression of CD44 prevents the cytotoxic effects of chemotherapy drugs in the treatment of various cancers. Therefore, high levels of CD44 in cancer patients are associated with poor disease prognosis [15]. CD44 is a potential marker of angiogenesis in OSCC and can be evaluated as a valuable biomarker of tumor invasion and also used as a therapeutic target for anti-angiogenic treatments [16]. Hyaluronic acid and its main receptor, CD44, are present everywhere in the body and have important structural and signaling roles. Dysregulation of hyaluronan-CD44 interactions can be seen in diseases such as inflammation and cancers [4,17].

Variability in CD44 expression patterns and its role in the behavior of cancer cells has been extensively studied, and recently there has been increased interest for CD44 evaluation as a CSCs marker in several tumor types. The results of a study conducted in 2016 showed that CD44 expression does not indicate aggressive behavior in SCC of the oral tongue, and as a result, CD44 cannot be considered a useful tool for determining tumor behavior, prognosis and 5-year survival rate of these tumors [18]. Of course, some studies such as the study by Zhang et al. in 2015 have reported contradictory results in this regard [40]. Since the exact expression and function of CD44 in metastatic processes and the involvement of human malignancies have not yet been determined, a meta-analysis seems to be necessary in this field.