oral cancer

Oral cancer poses a serious global health challenge due to its high morbidity and mortality rates, largely stemming from late-stage diagnosis and limited treatment success. Recent technological advances, particularly in artificial intelligence (AI), have opened new avenues for early detection and personalized treatment approaches.

This review aims to explore the role of AI, including machine learning (ML) and deep learning (DL), in the diagnosis, prognosis, and management of oral cancer. It also examines the systemic effects of oral cancer, underlying genetic and hormonal influences, and the impact of oxidative stress and chronic inflammation on disease progression.

A systematic literature review was conducted covering publications from 1997 to 2024, using PubMed, Scopus, and the Cochrane Library. Studies involving AI, ML, and DL in oral cancer detection and treatment were selected based on predefined inclusion and exclusion criteria. Bibliometric and trend analyses were also performed to assess global research output and collaborative networks.

AI techniques such as convolutional neural networks and support vector machines have demonstrated significant utility in early detection, histopathological analysis, and survival prediction. The review also highlights key genetic mutations (e.g., TP53, CDKN2A) and hormonal imbalances (e.g., estrogen, androgen receptors) linked to oral cancer pathogenesis. Furthermore, systemic involvement of organs like the liver, brain, and bone is discussed. Bibliometric data indicate increasing global collaboration and the emergence of AI as a dominant research focus in oral oncology.

AI-based diagnostic tools and predictive models offer promising pathways for early detection and personalized treatment in oral cancer. Understanding the molecular, systemic, and epidemiological dimensions of the disease, alongside leveraging computational advancements, can significantly enhance patient outcomes and support the development of precision medicine in oral oncology.

Shikonin, a compound extracted from Lithospermum erythrorhizon , has demonstrated therapeutic effects on cancer; however, its effects on oral cancer remain unclear.

This study aimed to explore the therapeutic value of shikonin for the treatment of oral cancer.

MTT, colony formation, and Transwell assays were employed to evaluate the inhibitory effects of shikonin on the proliferation and migration abilities of human oral cancer cell lines (SCC-4 and SAS). Apoptosis and cell viability were assessed using the TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay. To investigate the potential anticancer mechanisms of shikonin, RNA sequencing, quantitative PCR, and western blotting were performed to analyze changes in the expression levels of oral cancer cell-related genes and proteins (matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), VEGF-A, VEGF-C, Beclin-1, autophagy-related genes (ATG5), and light chain-3 (LC-3)). Additionally, animal xenograft experiments were conducted to examine the in vivo antitumor effects of shikonin.

The findings revealed that the external application of shikonin specifically targeted oral cancer cells without affecting normal cells and led to a dose-dependent inhibition of their growth. Even at non-lethal doses, shikonin effectively suppressed the production of metalloproteinases, thereby inhibiting cancer cell migration and wound healing. Furthermore, shikonin treatment reduced levels of tumor progression factors, such as vascular endothelial growth factor (VEGF)-A and VEGF-C, which are released during the early stages of cancer cell angiogenesis and lymphangiogenesis. Meanwhile, higher doses of shikonin induced cell autophagy and activated proteins such as ATG-5, LC-3B, and Beclin-1. At lethal doses, shikonin further decreased mitochondrial membrane potential, released calcium ions, and triggered apoptotic pathways. However, the administration of a calcium ion chelator (BAPTA-AM) inhibited shikonin-induced apoptosis.

These results demonstrate that shikonin induces autophagy and activates apoptotic pathways in oral cancer cells. Shikonin treatment significantly inhibited oral cancer growth and induced apoptosis in a rat model. In conclusion, shikonin effectively inhibited oral cancer cell growth, metastasis, and the expression of tumor progression-related proteins. Given the ease of drug delivery to the affected area in oral cancer, shikonin holds substantial potential for future applications that may improve patient recovery and enhance cure rates.

 Herpes simplex virus type 1 (HSV-1) infection contributes to oral carcinoma, but its carcinogenic role has not been elucidated yet. MicroRNAs (miRNAs) are involved in carcinogenesis. The aim of the present study was to examine the effect of HSV-1 infection on the expression of miR-29c, miR-221-5P, miR-21-5P, and miR-96-5P in patients with oral squamous cell carcinoma (OSSC).

 Twenty-five cases of OSCC and 25 samples of normal oral mucosa were examined in this study. The SYBR real-time polymerase chain reaction (RT-PCR) was completed to confirm the presence of HSV-1. The expressions of miR-29c, miR-221-5P, miR-21-5P, and miR-96-5P were measured using RT-PCR.

 The expression of miR-221-5P was significantly higher in OSCC with HSV-1 infection compared to non-infected cases (P=0.007). The expressions of miR-29c, miR-21-5P, and miR-96-5P were not significantly different between OSCCs with HSV-1 infection and controls (P=0.27, P=0.66, and P=0.23, respectively).

 HSV-1 infection had an up-regulation effect on miR-221-5P in OSCC. This finding proposes a novel mechanism for HSV-1 infection in the development of OSCC.

Over the past 5 years, the use of immune checkpoint inhibitors in the treatment of head‑and‑neck squamous cell carcinoma (HNSCC) has increased. Both programmed death-ligand 1 (PD‑L1) and cluster of differentiation 68 (CD68) are overexpressed in various carcinomas. Consequently, evaluating the expression of CD68 and PD‑L1 in HNSCC lesions may lead to detecting a possible marker for HNSCC. This study aimed to evaluate the expression of PDL1 and CD68 markers in a patient with oral squamous cell carcinoma (OSCC) and examine its relationship with depth of invasion (DOI) and immunofluorescence (IF) through immunohistochemistry.

This cross‑sectional study was conducted in the School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, Department of Oral and Maxillofacial Pathology. Thirty‑four paraffin blocks and demographic information of 15 female and 19 male OSCC patients were collected. Following sample preparations, immunohistochemical staining was performed. Subsequently, each tissue section was analyzed for tumor‑infiltrating lymphocytes by CD68 marker and PD‑L1 expression. Data analysis was conducted using SPSS software (version 25). Chi‑square, Shapiro–Wilk, and independent t‑analytical tests were employed for statistical assessments. P < 0.05 was remarked as statistically significant.

CD68 and PDL1 expression in the squamous cell carcinoma (SCC) group was higher than the control group (P < 0.001). There was an increasing expression of PDL1 and CD68 as the grade of the disease progressed (P < 0.001 for each), as well as an increasing expression of IF and DOI.

The expression levels of CD68 and PDL1 were elevated in SCC tissues in comparison to the unaffected, healthy parts of the tissue section.

Oral cancer (OC) remains a prominent cause of mortality worldwide. Eriodictyol (ERD) is a natural flavonoid that has been documented to exert antioxidant, anti-inflammatory, and anti-tumor activities. However, the precise role and the antitumor mechanism of ERD on OC are still uncertain.  

Hence, this study intended to explore the potential anticancer activity and underlying apoptotic mechanisms of ERD (30 and 40 µM/ml) in human oral squamous cell carcinoma (OSCC) SCC131 cells. The ERD activity on SCC131 cells cytotoxicity, intracellular ROS, apoptosis, MAPK/STAT-3 and P13K/AKT signaling pathways was assessed by MTT test, DCFH-DA, AO/EB, DAPI, PI, RT-PCR, and western blot analysis.  

Our results uncovered that ERD could inhibit SCC131 cell viability, ROS accumulation, and enhanced apoptosis in a quantity dependent mode. ERD also alleviates the mRNA expression level of pin-1, STAT-3, p38, JNK, and p65 along with the protein level expression of the P13K/AKT signaling pathway as evidenced by western blot.  

Our data established that ERD attenuates SCC131 cell proliferation by ROS-mediated apoptosis through the inhibition of MAPK/STAT-3 and P13K/AKT signaling pathways suggesting that ERD is a potential natural remedy for OSCC.

Andrographolide has been studied on different types of human cancer cells, but very few studies have been conducted on oral cancer. The study aimed to evaluate the anticancer potential of Andrographolide on an oral cancer cell line (KB) through in-silico network analysis and in vitro assays.

The in-silico analysis involved the determination of drug-likeness prediction, prediction of common targets between oral cancer and andrographolide, Protein-Protein Interactions (PPI), hub genes, top 10 associated pathways by Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, Gene Ontology (GO), and molecular docking experiments. In vitro assays comprised MTT assay, apoptosis assay, cell cycle analysis, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP), anti-migration activity, and gene expressions using Polymerase Chain Reaction (PCR).

Fifteen common genes were obtained and were seen to be involved in cellular proliferation, regulation of apoptosis, migration of cells, regulation of MAPK cascade, and regulation of cell cycle. The most common genes involved in the top 10 pathways were MAPK1, MAPK8, MAPK14, and IL6 which were seen to be associated with the MAPK signaling pathway which may be the key pathway through which andrographolide may aid in treating oral cancer. In vitro assays showed anti-proliferative properties, late apoptosis, and anti-migratory properties.

According to the results obtained, andrographolide has shown anticancer properties and has the potential to be used as a chemotherapeutic drug. The in-silico approach used in the present study can aid as a model for future research in developing efficient cancer treatments.

Oral cancer is one of the most common cancers in the world. The on sequences of oral cancer and the complications of its treatments have an adverse effect on the quality of life of patients. Many people with cancer consider the management of problems related to this disease and its treatment as a part of their life. Self-management education through phone-based applications enables oral cancer patients to actively and independently engage in self-care and increases their responsibility in controlling symptoms and complications.

Oral squamous cell carcinoma is a multifactorial disease that is the sixth most common cancer worldwide. MicroRNAs have been confirmed to play a role in oral squamous cell carcinoma, acting as either oncogenes or tumor suppressor genes. This study examined the expression level and role of microR-148 and microR-375 in oral cancer.

In this study, we used 30 cancer samples with infection and 30 cancer samples without infection. To analyze the expression of microRNA 375 and microRNA 148, we used real-time PCR. First, we extracted total RNA from the samples. Then, we generated cDNA from it. Finally, the obtained cDNA was used in the real-time PCR technique.

In cancer patients with oral infection, there was an increase in microRNA-148 expression and a decrease in microRNA-375 compared to cancer patients without oral infection.

The downregulation of microRNA-375 and upregulation of microRNA-148 can be utilized as diagnostic biomarkers and prognostic factors in oral cancer.

This study aims to compare the efficacy between conventional exfoliative cytology (EC) and centrifuged liquid‑based cytology (CLBC) in control, leukoplakia, and oral squamous cell carcinoma (OSCC) patients. Oral leukoplakia and oral cancer require an early definitive diagnosis for better prognostic outcome. Oral EC, a minimally invasive technique that involves the examination of desquamated cells from the tissue surfaces used as a method of early diagnosis. CLBC is a modified technique that is used to achieve improved quality of the cytology findings.

A comparative study was done in 30 subjects, of which, 10 cases from control group, 10 oral leukoplakia, and 10 OSCC cases. These subjects were selected according to the appropriate inclusion and exclusion criteria. The cases in each group underwent conventional as well as CLBC. The comparison was carried out between these groups with respect to the cellular and background stromal factors. Appropriate qualitative evaluation of the samples was collected and statistical analysis was done using the Chi‑squared test. The significance level of value was P < 0.05.

Significant results were obtained for certain parameters such as cellular overlap clear background, uniform distribution in control, leukoplakia, and OSCC with a P = 0.004**, P = 0.001**, P = 0.006** using CLBC.

CLBC is better and give clearer vision as compared to conventional cytology and can be used in the early diagnosis.

In a recently published article (IJMS issue: Volume 49, number 3, March 2024), Parchami and colleagues investigated various Human Papillomavirus (HPV) detection methods in HPV-associated oral epithelial dysplasia (HAOED) cases.

The use of shark cartilage as a supplementary treatment has a long yet unresolved history in the realm of complementary-alternative medicine. This study aimed to investigate the impact of concentrated and purified extracts from Persian Gulf shark cartilage (PGSC) on oral cavity squamous cell carcinoma (SCC) (specifically, the KB cell line) induced in an animal model.

Ectopic tumors of oral cavity SCC were induced in eight nude mice through the heterotransplantation of the KB cell line. Once the tumor volume reached 100 mm3, the mice were randomly divided into two groups: treatment and control. The treatment group received shark cartilage at a dosage of 50 mg/kg body weight, while the control group received a phosphate buffer. The drug was administered daily for four days via the intraperitoneal route. Following this, the drug administration was halted for a period of five days before resuming (as per the NCI protocol). After 54 days, the animals were sacrificed, and their tumors were sent for immunohistochemical evaluation using Ki-67 and CD34 markers.

The findings revealed a significant reduction in intratumoral blood vessels in the treatment group compared to the control group (P-value = 0.001). While there was a decrease in both the size of the tumor and the proliferation of tumor cells, this reduction was not statistically significant. The average proliferation index was 13.33% for the treatment group and 33.33% for the control group.

 Significant decrease in intra-tumoral vascularity can control tumor spreading and metastasis, potentially playing an important role in cancer management of oral cavity SCC.

Diagnosis of oral cancer in the early stages is the most effective tool to improve survival and reduce complications caused by the disease. The aim of this study was investigating the dental patients’ knowledge of oral cancer in Isfahan.

This descriptive cross‑sectional study was performed on 334 patients referred to dental centers in Isfahan, Shahinshahr, Najafabad, Khomeini Shahr, Harand, and Zarrinshahr cities. Data were collected by a researcher‑made 25‑item questionnaire. Data analysis was carried out by SPSS (version 26) software using the independent t‑test, one‑way analysis of variance, and Pearson correlation coefficient (P < 0.05).

The patients’ mean score of knowledge was 49.3 ± 21.4 in Isfahan city and 53.1 ± 18.4 in the other cities of Isfahan province. There was no significant difference between knowledge of oral cancer and gender, marital status, and residence, but there was a significant difference between employment status and knowledge (P = 0.03). The mean score of knowledge was significantly higher in patients who had a history of oral cancer in relatives than in other patients (P = 0.03). Virtual networks (Telegram, WhatsApp, and Instagram), journals, and books were the most common sources for patients about oral cancers.

Dental patients’ knowledge of oral cancer in Isfahan province and its cities was moderate, so it is necessary to increase their level of knowledge through more education.

A 39-year-old male was referred to the Oral and Maxillofacial Medicine department of Alborz University of Medical Sciences Dental School with a lesion that he had noticed for 3 weeks. The patient had no signs or symptoms and no cigarette and alcohol consumption. Because the lesion was placed at the lateral posterior portion of the tongue which is a common place for oral malignancies a biopsy was done. The pathology result was Squamous cell carcinoma grade 2. The patient was referred to Imam Khomeini Cancer Institute for further treatment.

Oral squamous cell carcinoma (OSCC) research is still inconclusive due to methodological differences and constraints. The study aimed to review the function of oral microflora in the progression of oral cancer and to highlight the need for good oral hygiene practices for various reasons beyond only avoiding dental problems such as cavities and gum disease. Oral carcinoma is a rapidly increasing cancer with a high mortality rate, particularly in adolescents and young adults. Despite the progress of chemotherapy and radiation therapy, the percentage of people who will be alive is less than 50% after 5 years. Oral cancer has a terrible prognosis and can spread if it is not detected early; thus, researchers should focus on developing biomarkers that might detect the disease at an earlier stage. SCC has a complex set of causes. Factors and conditions predisposing to oral cancer include tobacco, alcohol, infections (e.g., candidiasis), viruses (human immunodeficiency virus, herpes simplex virus, and human papillomavirus), and systemic conditions (iron deficiency anemia, malnutrition, and vitamin A deficiency). Changes in the structure of oral bacteria are caused by two primary risk factors for oral cancer, including smoking and alcohol consumption. These microorganisms produce carcinogenic products such as acetaldehyde, which are associated with oral cancer. The oral cavity is host to a wide variety of microflora, including fungi, bacteria, viruses, and other microorganisms, as one of the most abundant microbial habitats in the human body. Recent epidemiological research has linked specific periodontitis microorganisms to an increased risk of developing oral premalignant and neoplastic lesions. Clinicians have long noted a correlation among dental state, poor oral hygiene, and oral cancer, which may be independent of tobacco and alcohol use. Based on the results, more research is required to determine the precise results and the nature of the correlation between oral microbiota and oral cancer, considering the findings of the previous studies.

 Oral and oropharyngeal cancer is known as one of the few lethal oral diseases with a great burden associated with a high cost of treatment and rehabilitation, life-long impairments, and a nearly 50% mortality rate; therefore, it should be considered an increasingly severe health and social problem in the world due to its increased incidence. This makes the burden of oral and oropharyngeal cancer very high, with a hefty economic burden.

 The current study was designed and conducted to investigate epidemiological features of oral and oropharyngeal cancer in the Khuzestan province of Iran.

 This cross-sectional study was conducted with raw data on cancer incidence obtained from the Khuzestan cancer registry as a subsequent of the Iranian population-based national cancer registry from 2014 to 2019. Recorded cases were standardized by ICD-10 and ICD-O-3 classifications and categorized by gender, age group, diagnosis, etc. The method of diagnosis in this study consisted of four categories. Descriptive data for the frequency and rate of each variable and analyses of associations between variables were conducted using the chi-squared test with a statistical significance of P < 0.05.

 A total of 941 valid cases were identified in the study period, with a composition of males 675 cases and females 266 cases in total. More than 85% of reported cases were submitted to a database with pathologic reports, verifying a high data validity level. The crude rate in female cases had an upward trend in contrast to the crude rate in males, which shows a downward trend. Squamous cell carcinoma was the most diagnosed malignancy, with 532 cases (55%).

 The data on oral and oropharyngeal cancer in Khuzestan suggest that the overall incidence of the disease increased, particularly in females and younger age groups in the study period. Concerning increasing trends and the presence of most oral and oropharyngeal cancer cases in the active and young members of society of Khuzestan province of Iran, an extensive program for screening, prevention, and rehabilitation should be prioritized.

Metastatic lesions of the jaws are a diagnostic challenge because of their scarcity and uncharacteristic clinical-radiographic features. Carcinoma of unknown primary origin (CUP) is characterized by the existence of metastatic disease with no recognized primary neoplasm after a comprehensive work-up. CUP shows a poor prognosis with limited treatment choices. This paper presents a 64-year-old male with a chief complaint of paresthesia of the chin and lower lip. Panoramic radiography showed an ill-defined radiolucency in the left mandibular molar area and the residue of the first molar root. Microscopic examination demonstrated features of mucin-producing adenocarcinoma and was not similar to common neoplasms of the jaw. The whole-body scan revealed multiple osseous uptakes. CDX2 was diffusely positive. However, in the end, the origin of the primary tumor was not determined. Considering the aforementioned data, the diagnosis of metastatic adenocarcinoma with unknown primary origin was made. CUP of the oral cavity is an extremely rare event. The possibility of metastasis should be raised in a patient who complains of paresthesia. Awareness of the clinical and histopathologic features of these malignancies is crucial for clinicians and pathologists to have a proper diagnosis.

Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV–Vis spectra. The in vitro cytotoxicity screening assay suggested promising activity against TSCCF with IC50 of 446.68 µg/mL, but insignificant activity against NHGF cells (IC50 of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.

Cancer is a disorder with a high mortality rate that leads to many psychological and economic conflicts. Herbal compounds that induce apoptosis are one of the methods for the treatment of cancer. The aim of the present study was to evaluate the anticancer effects of hydroxytyrosol on oral cancer cell line KB and the regulation of BAX and BCL2 genes expression.

Anti-proliferation effects of hydroxytyrosol against oral cancer cell line KB were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Moreover, mRNA expression of BAX and BCL2 genes were investigated by quantitative Real-Time PCR method.

We observed a significant decrease in proliferation of the oral cancer cell line treated with hydroxytyrosol. In addition, expression of BAX and BCL2 genes was significantly increased (3.3 fold) and decreased (2.2 fold) in the oral cancer cell line treated with Hydroxytyrosol, respectively (P < 0.05).

The study indicated a high antiproliferation effect of hydroxytyrosol against oral cancer cell line KB through regulating the expression of some apoptotic genes.

Moringa oleifera is a considerable ethnomedical herb with various bioactive compounds. This study aimed to analyze the efficacy of M. oleifera in the prevention and management of various oral conditions. A thorough search was conducted on the Web of Science, Scopus, PubMed, and PubMed Central databases. After screening the data on the basis of inclusion and exclusion criteria, 9 studies were considered for further meta-analysis. The analysis was performed on R programming software (version R-4.0.2) and the results were represented by a forest plot. The estimate obtained via common and random effects model for in vitro studies was statistically insignificant (I2 test P > 0.05) with risk ratios of 8.25 (95% CI: 3.76-18.08) and 7.98 (95% CI: 3.64-17.50) and for in vivo studies were statistically significant (I2 test P )0.05 < with risk ratios of 1.12 (95% CI: 0.90-1.40) and 0.97 (95% CI: 0.71-1.32), indicating the efficacy of M. oleifera in oral diseases on animal and clinical trials, whereas it failed to report the efficacy on in vitro level. Future research has to be done to come up with new and more phytoactive compounds from all parts of the plant with proper extraction procedures. The effectiveness of the compounds has to be validated first on in vitro scale followed by clinical trials so that M. oleifera can be used as therapy in preventing and managing oral ailments.