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Oral Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Salivary Gland Cancer
Molecular Biology of Oral Cancers

Information Patients and the Public (12 links)

Information for Health Professionals / Researchers (13 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Liu CJ, Fang KH, Chang CC, et al.
Application of "parachute" technique for free flap reconstruction in advanced tongue cancer after ablation without lip-jaw splitting: A retrospective case study.
Medicine (Baltimore). 2019; 98(33):e16728 [PubMed] Related Publications
The hemi or subtotal/total glossectomy is usually approached by lip-jaw splitting procedure for advanced tongue cancer ablation. This highly invasive procedure can cause facial disfiguration, bone malunion, and osteoradionecrosis. The aim of this study is to compare the surgical outcome in free flap tongue reconstruction between novel parachute technique in an intact jaw and the conventional lip-jaw splitting procedure after tongue cancer ablation.In this study, parachute technique was adopted for free flap inset in patients without mandibulotomy. We retrospectively reviewed patients who have received primary advanced tongue cancer resection and free flap reconstruction during April, 2008 to January, 2015. Patients were divided into 2 groups. Group A was undergoing parachute technique without lip-jaw splitting. We sutured all the strings through the edges of defect in the first step and through the matching points of flap margin in the second step from outside the oral cavity. Then, the strings were pulled and the flap was parachuted down on the defects after all the matching points were tied together. In group B, the patients received conventional lip-jaw splitting procedure. Student t test was used for results analysis.There were 15 patients (n = 15) in group A and 15 patients (n = 15) in group B. In the patients receiving parachute technique, operation time showed 34 minutes (P = .49) shorter, hospital stay showed 4 days (P = .32) shorter, and the infection rate of surgical site showed 6.6% (P = .64) less than with conventional technique. The survival rates of the flaps were both 100% without revision.The parachute technique is an effective and more accessible method for free flap setting in cases of tongue reconstruction without lip-jaw splitting, and provides patients with better aesthetic appearance.

Zhao R, Jia T, Qiao B, et al.
Nomogram predicting long-term overall survival and cancer-specific survival of lip carcinoma patients based on the SEER database: A retrospective case-control study.
Medicine (Baltimore). 2019; 98(33):e16727 [PubMed] Related Publications
Our study was designed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of lip carcinoma patients.A search of the Surveillance, Epidemiology, and End Results (SEER) database provided us with detailed clinical data of the 1780 lip carcinoma patients. On the basis of the credible random split-sample method, the 1780 patients were placed into 2 groups, with 890 patients in the modeling group and 890 patients in the counterpart's group (proportion = 1:1). By employing Kaplan-Meier univariate and Cox multivariate survival analyses based on the modeling cohort, the nomograms were developed and then used to divide the modeling cohort into low-risk cohort and high-risk cohort. The survival rates of the 2 groups were calculated. Internal and external evaluation of nomogram accuracy was performed by the concordance index (C-index) and calibration curves.With regard to 5- and 8-year OS and CSS, the C-indexes of internal validation were 0.762 and 0.787, whereas those of external validation reached 0.772 and 0.818, respectively. All the C-indexes were higher than 0.7. The survival curves of the low-risk cohort were obviously better than those of the high-risk cohort.Credible nomograms have been established based on the SEER large-sample population research. We believe these nomograms can contribute to the design of treatment plans and evaluations of individual prognosis.

Tomasovic-Loncaric C, Fucic A, Andabak A, et al.
Androgen Receptor as a Biomarker of Oral Squamous Cell Carcinoma Progression Risk.
Anticancer Res. 2019; 39(8):4285-4289 [PubMed] Related Publications
BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC.
PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry.
RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients.
CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.

Chakraborty D, Natarajan C, Mukherjee A
Advances in oral cancer detection.
Adv Clin Chem. 2019; 91:181-200 [PubMed] Related Publications
High incidence of oral carcinoma and its late-stage presentation are the major global healthcare issues. The World Health Organization (WHO) has set early diagnosis and prevention of oral cancer as their primary objective. It is important to consider the time of oral screening, as it plays a pivotal role in understanding the disease prognosis. Critical signs and symptoms that can be identified during initial oral screening can improve the chances of patient's survival. Reports suggest that socio-economic factors, lack of public awareness and delays from primary health care centers are few of the major parameters that contribute to patient's mortality and morbidity. Conventional technique of visual examination of the oral lesion can effectively monitor patient mortality when exposed to risk factors. However, several disadvantages limit the clinical utility of this technique. Thus, screening aids that efficiently differentiate between a benign and malignant lesion as well as deliver information about early OSCC can ameliorate the complications associated with oral cancer diagnosis. Recent advances in optical imaging systems, such as tissue-fluorescence imaging and optical coherence tomography have been proved to be considerably efficient. Additionally, extensive research has been directed towards nanoparticle-based immunosensors, DNA analysis, and salivary proteomics. However, lack of proper clinical trials and correlation with biopsy result hinder the usage of these screening techniques in clinics. In this review, we highlight the importance of early diagnosis of oral cancer as well as discuss about the effectiveness and limitations of the recent diagnostic aids. It can be stated that public awareness regarding routine oral examination and employing screening methods that are non-invasive, robust, and economic, would enhance early stage diagnosis of oral cancer and have a positive impact on patient's survival.

Ghani WMN, Ramanathan A, Prime SS, et al.
Survival of Oral Cancer Patients in Different Ethnicities.
Cancer Invest. 2019; 37(7):275-287 [PubMed] Related Publications
Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.

Liu W, Zhang Y, Wu L, et al.
Characteristics and trends of oral leukoplakia research: A bibliometric study of the 100 most cited articles.
Medicine (Baltimore). 2019; 98(27):e16293 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Bibliometric analysis highlights the key topics and studies which have shaped the understanding and management of a disease of interest. Here the top-cited articles on oral leukoplakia (OL) were characterized, and research patterns and trends were analyzed.
METHODS: A comprehensive search was performed and identified in the Scopus database up to 22 February 2019 for the 100 most-cited articles on OL.
RESULTS: The number of citations of the 100 selected articles varied from 116 to 1418, with a mean of 226.7 citations per article. Both Journal of Oral Pathology and Medicine and Oral Surgery Oral Medicine Oral Pathology Oral Radiology were journals with the most articles published (n = 10). Both Hong W.K. and Lippman S. were the most frequently contributing authors (n = 9). United States (n = 43) and M.D. Anderson Cancer Center (n = 12) was most contributing country and institution, respectively. Systematic reviews/meta-analysis (n = 3) and randomized controlled trial (n = 7) were study designs with high evidence level. It is noteworthy that the majority of high-quality articles were the research of chemopreventive drugs (n = 21) and molecular markers/targets (n = 10), which may indicate a trend of key topics.
CONCLUSIONS: The results of this first citation analysis of the most-cited articles on OL provide a historical perspective on scientific evolution, and suggest further research trends and clinical practice in the field of OL.

Zhu Y, Zhang H, Li C
The clinical application of partial removal periodontal surgery in the therapy of epulis.
Medicine (Baltimore). 2019; 98(27):e16107 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The aim of this study was to compare the clinical effects between traditional surgery and minimally invasive periodontal surgery in the treatment of epulis.
METHODS: A total of 33 cases of patients diagnosed with fibrous epulis were randomly divided into traditional surgery group and minimally invasive periodontal surgery group. After the different procedures, several parameters were detected to evaluate the effects of minimally invasive periodontal surgery.
RESULTS: Preoperative bleeding index and plaque index, adopt rank, and test showed no significant differences between the 2 groups. After 12 weeks, gingival papilla filling index in experiment group is statistically higher than control group, and shows the statistical differences (P < .05). The width of keratinized gingiva in experiment group grew more than that in control group, and showed the statistical differences (4.68 ± 0.30 vs 3.00 ± 0.28 mm, P < .05). No recurrence of fibrous epulis was found during the subsequent 6 months to 2 years follow-up after the surgeries.
CONCLUSION: Minimally invasive periodontal surgery that reserved tumor epithelium could have a better effect than the traditional surgery in the selected patients.

Kim BY, Cho KR, Sohn JH, Kim JY
Sarcomatoid carcinoma after radiotherapy for early-stage oral squamous cell carcinoma: Case report.
Medicine (Baltimore). 2019; 98(27):e16003 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Sarcomatoid carcinoma is a rare variant of squamous cell carcinoma (SCC) with poor prognosis. Previous radiation has been reported as one of the etiologic factors.
PATIENT CONCERNS: We describe a case of a 57-year-old man presented with a painless mass in the left supraclavicular area. Five years before, he was diagnosed with SCC in floor of mouth (FOM) and underwent radiotherapy (RT).
DIAGNOSES: Sonography-guided biopsy on the supraclavicular lymph node revealed diffuse spindle cell proliferation with a focus of squamous differentiation. Local recurrence on primary site or distant metastasis was not obvious on both computed tomography (CT) of the neck and F-fluorodeoxyglucose positron emission tomography CT. The final diagnosis was confirmed as sarcomatoid carcinoma via surgery.
INTERVENTIONS: The patient underwent surgery including explorative resection of the mouth floor, excision of the submandibular gland, and modified radical neck dissection. Following surgery, the patient received adjuvant radiation therapy.
OUTCOMES: There were no complications according to the surgery. Six months after adjuvant therapy, distant metastasis to liver was identified. The patient is currently undergoing palliative chemotherapy.
LESSONS: This may be the first reported case of sarcomatoid carcinoma arising from early-stage SCC in FOM that was previously treated with RT alone. When RT is performed as a single modality for oral SCC, even in an early stage, rigorous follow-up should be performed.

Uchida S, Kobayashi K, Ohno S, et al.
Induction of Non-Apoptotic Cell Death by Adrenergic Agonists in Human Oral Squamous Cell Carcinoma Cell Lines.
Anticancer Res. 2019; 39(7):3519-3529 [PubMed] Related Publications
BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes.
MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage.
RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine.
CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.

Imanari K, Hashimoto M, Wakabayashi H, et al.
Quantitative Structure-Cytotoxicity Relationship of Azulene Amide Derivatives.
Anticancer Res. 2019; 39(7):3507-3518 [PubMed] Related Publications
BACKGROUND/AIM: Very few studies of anticancer activity of azulene amides led us to investigate the cytotoxicity of 21 N-alkylazulene-1-carboxamides introduced either with 3-methyl

Sun W, Cheng M, Zhuang S, et al.
Nomograms to predict survival of stage IV tongue squamous cell carcinoma after surgery.
Medicine (Baltimore). 2019; 98(26):e16206 [PubMed] Free Access to Full Article Related Publications
To develop clinical nomograms for prediction of overall survival (OS) and cancer-specific survival (CSS) in patients with stage IV tongue squamous cell carcinoma (TSCC) after surgery based on the Surveillance, Epidemiology, and End Results (SEER) program database.We collected data of resected stage IV TSCC patients from the SEER database, and divided them into the training set and validation set by 7:3 randomly. Kaplan-Meier analysis and Cox regression analysis were adopted to distinguish independent risk factors for OS and CSS. Clinical nomograms were constructed to predict the 3-year and 5-year probabilities of OS and CSS for individual patients. Calibration curves and Harrell C-indices were used for internal and external validation.A total of 1550 patients with resected stage IV TSCC were identified. No statistical differences were detected between the training and validation sets. Age, race, marital status, tumor site, AJCC T/N/M status, and radiotherapy were recognized as independent prognostic factors associated with OS as well as CSS. Then nomograms were developed based on these variables. The calibration curves displayed a good agreement between the predicted and actual values of 3-year and 5-year probabilities for OS and CSS. The C-indices predicting OS were corrected as 0.705 in the training set, and 0.664 in the validation set. As for CSS, corrected C-indices were 0.708 in the training set and 0.663 in the validation set.The established nomograms in this study exhibited good accuracy and effectiveness to predict 3-year and 5-year probabilities of OS and CSS in resected stage IV TSCC patients. They are useful tools to evaluate survival outcomes and helped choose appropriate treatment strategies.

Lu T, Liang WZ, Hao LJ, et al.
Action of chlorzoxazone on Ca
Chin J Physiol. 2019 May-Jun; 62(3):123-130 [PubMed] Related Publications
Chlorzoxazone is a skeletal muscle relaxant. However, the effect of chlorzoxazone on intracellular Ca

Imai A, Mochizuki D, Misawa Y, et al.
DNA Cell Biol. 2019; 38(7):678-687 [PubMed] Related Publications
Staging and pathological grading systems are convenient, but imperfect predictors of recurrence of head and neck squamous cell carcinoma. Therefore, to identify potential alternative prognostic markers, we investigated the methylation status of the promoter of Sal-like protein 2 (

Israel Y, Rachmiel A, Gourevich K, Nagler R
Kaplan-Meier analysis of salivary gland tumors: prognosis and long-term survival.
J Cancer Res Clin Oncol. 2019; 145(8):2123-2130 [PubMed] Related Publications
PURPOSE: We evaluated the impact of various tumor related parameters on survival probability in a cohort of patients with malignant salivary tumors, using the Kaplan-Meier analysis.
METHODS: We measured patients up to 15 years following therapy, looking at T N M stage, grade perineural invasion and extra-parenchymal spread.
RESULTS: Of 101 patients diagnosed with various salivary malignant tumors in our medical center, 79 patients survived while 22 died with disease (DWD). The impact of distant metastasis (M+) was devastating (survival probability at 60 months and at 180 months dropped from 0.93 (M-) to 0.40 (M+) and from 0.67 to 0.40, respectively, p = 0.0001), the impact of perineural invasion was severe (at 180 months the probability of survival dropped from 0.75 to 0.21, p = 0.002). Higher stage tumor also decreased survival (from 0.82 to 0.53 at 180 months, p = 0.002) as did poor histological grade (from 0.85 to 0.48 at 180 months, p = 0.019). Neck metastasis (N+) impact was quite moderate (at 180 months the probability of survival dropped from 0.69 to 0.58, p = 0.044) while neither tumor size (T) nor extra-parenchymal spread significantly affected survival.
CONCLUSIONS: Salivary tumor location and its potential to infiltrate nerves and blood vessels and to metastasize is the most telling parameter. Systemic therapy aimed at halting distant metastatic spread is the most effective therapeutic goal. Dissection of N0 neck metastasis is not necessarily a valuable treatment.

Zhang D, Liao X, Tang Y, et al.
Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls.
Anticancer Res. 2019; 39(6):3213-3217 [PubMed] Related Publications
BACKGROUND: Warthin-like mucoepidermoid carcinoma is a newly recognized rare entity and could be misdiagnosed as a benign Warthin tumor. We report such a case of a 36-year-old male who presented with a left parotid gland mass.
CASE REPORT: Fine-needle aspiration showed features suggestive of Warthin tumor. Following parotidectomy, grossly there was a 1.6 cm well-circumscribed multilobular mass with focal areas of cystic change. Microscopically, at low magnification it had histological features resembling Warthin tumor, while lining with squamoid cells with scattered mucocytes demonstrating mild cytologic atypia was observed at high magnification. Immunohistochemically, the tumor cells were positive for p40, p63, cytokeratin 5/6, cytokeratin 7, and cancer antigen 125, but negative for discovered on GIST-1 (DOG1). Mucicarmine stain highlighted intracellular mucin within mucocytes. Rearrangement of mastermind like transcriptional coactivator 2 (MAML2) (11q21) gene was shown to be present in tumor cells by fluorescence in situ hybridization, supporting the diagnosis of a low-grade Warthin-like mucoepidermoid carcinoma. The patient was disease-free 12 months after surgery.
CONCLUSION: Warthin-like mucoepidermoid carcinoma has not been widely recognized and can be misdiagnosed as Warthin tumor. Testing for MAML2 rearrangement provides essential support for diagnosis in difficult cases.

Takahashi H, Sakakura K, Arisaka Y, et al.
Clinical and Biological Significance of PD-L1 Expression Within the Tumor Microenvironment of Oral Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(6):3039-3046 [PubMed] Related Publications
BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1) expression in tumor cells is regulated by a close interrelation between tumor and stromal cells within the tumor microenvironment. Our aim was to evaluate the clinical and biological significance of PD-L1 expression in oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS: PD-L1, cluster of differentiation (CD)4, CD8, and forkhead box P3 (FOXP3) expression in tumor tissues obtained from 77 patients with OSCC was evaluated by immunohistochemical staining, and then analyzed for associations with clinical and biological factors.
RESULTS: Among the clinicopathological factors tested, only vascular invasion showed a trend toward lower PD-L1 expression (p=0.05). Metabolic tumor volume (MTV), and total lesion glycolysis (TLG) significantly positively correlated with PD-L1 expression (MTV, p=0.04; TLG, p=0.03). In patients with OSCC with high PD-L1 expression, those whose tumors had abundant infiltrating CD4
CONCLUSION: As regulation of PD-L1 expression is complex, its evaluation combined with other markers may be useful to determine clinical applications of PD-L1 expression.

Huang SJ, Tseng YK, Lo YH, et al.
Association of
Anticancer Res. 2019; 39(6):2891-2902 [PubMed] Related Publications
BACKGROUND/AIM: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC.
MATERIALS AND METHODS: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method.
RESULTS: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype.
CONCLUSION: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

Liu C, Jiang YH, Zhao ZL, et al.
Knockdown of Histone Methyltransferase WHSC1 Induces Apoptosis and Inhibits Cell Proliferation and Tumorigenesis in Salivary Adenoid Cystic Carcinoma.
Anticancer Res. 2019; 39(6):2729-2737 [PubMed] Related Publications
BACKGROUND/AIM: Salivary adenoid cystic carcinoma (SACC) is the most common malignancy of the salivary gland with a poor prognosis and survival. The present study aimed to investigate the role of histone methyltransferase WHSC1 in SACC.
MATERIALS AND METHODS: Human SACC specimens were evaluated for WHSC1 expression by RT-PCR and immunohistochemistry. The effects of WHSC1 knockdown on SACC cells proliferation, cell cycle, clone and tumorsphere formation, and apoptosis as well as on the expression of related genes were examined. A xenograft mouse model of SACC was used to evaluate the in vivo effects of WHSC1 knockdown on SACC tumorigenesis.
RESULTS: WHSC1 expression was up-regulated in human SACC tissues (p<0.01). WHSC1 knockdown in SACC cells significantly inhibited cell proliferation, clone and tumorsphere formation (p<0.05). Cell distribution at the S and G
CONCLUSION: Knockdown of WHSC1 inhibited cell proliferation, induced apoptosis and affected tumorigenesis in SACC.

Rini MS, Zerbo S, Ventura Spagnolo E, et al.
Oral cancer and treatment information involved in therapeutic decision-making.
Clin Ter. 2019 May-Jun; 170(3):e216-e222 [PubMed] Related Publications
BACKGROUND: Early detection of oral cancer improves survival after treatment and the quality of life. The adoption of standardized methodological protocols of screening has increased the possibilities for early identification and appropriate treatment. The informed consent must be obtained by patients before any treatment and/or surgical procedure. The clinical and surgical details must be discussed with the patient, as well as potential risks and benefits. Consent must be documented in the medical record and consent forms may serve to document the physician's discussion with the patient.
OBJECTIVES: all dentists are trained to detect the early signs of oral cancer. The health professional have a key role in identify the early signs of oral cancer in order to plan the treatment and management of the disease. The work aims to provide simple practical information to collect the patient's consent and encouraging him to improve healthy behaviors.
MATERIALS AND METHODS: are analyzed the critical issues of clinical practice in order to improve the management of oral cancer.
RESULTS AND CONCLUSIONS: Identify effective information approaches documented in the medical record as a tool of close communication between the patient and the physician.

Tang JY, Li LJ, Ou-Yang F, et al.
Ethyl Acetate Extract of
DNA Cell Biol. 2019; 38(8):763-772 [PubMed] Related Publications

Tabrizi R, Farahani Z, Barouj MD, et al.
What Is a Safe Distance for Preservation of the Inferior Alveolar Nerve in Lower Gingival Squamous Cell Carcinoma? A Radiographic and Histopathological Study.
J Craniofac Surg. 2019; 30(4):e327-e330 [PubMed] Related Publications
PURPOSE: Involvement of the inferior alveolar nerve (IAN) is important in the prognosis and treatment of gingival squamous cell carcinoma (SCC).
METHODS: In this cross sectional study, patients with gingival SCC (T4a), undergoing hemimandibulectomy or subtotal hemimandibulectomy, were examined. The distance between the lesion and inferior alveolar canal (IAC) was measured, using axial computed tomography scans before resection. Following that, histopathological evaluation of IAN was conducted. The receiver operating characteristic curve was plotted to determine the association of IAN involvement in histopathological evaluation with various distances between the lesion and IAC.
RESULTS: A total of 29 patients were examined in this study. The mean distance between the lesion and IAC was 9.40 ± 2.21 mm. Nerve involvement was documented in 9 (45%) out of 20 males, while 11 (55%) men showed no involvement. Thirteen (44.82%) patients showed IAN involvement. The receiver operating characteristic curve demonstrated a cut-off point of 9.75 mm for the lesion-IAN distance. The possibility of IAN involvement was 23.33 times higher in patients who reported paresthesia, compared with patients without nerve involvement (odds ratio, 23.33; 95% CL; P = 0.001) CONCLUSION:: It seems that in a CT scan view, a 9.75-mm safe margin is associated with high accuracy for preserving IAN in patients with gingival SCC. Also, neurosensory disturbance can be considered a strong predictor of IAN involvement.

Seok J, Jeong WJ, Ahn SH, Jung YH
The growth rate and the positive prediction of needle biopsy of clinically diagnosed Warthin's tumor.
Eur Arch Otorhinolaryngol. 2019; 276(7):2091-2096 [PubMed] Related Publications
PURPOSE: This study reports the clinical course, including the growth rate, of Warthin's tumor (WT) and evaluates the positive prediction of needle biopsy for WT.
METHODS: The medical records of 182 patients clinically diagnosed with WT were retrospectively reviewed. Tumor growth rates were measured in patients who underwent serial radiologic exams with minimum 6-month time intervals, and the positive prediction value (PPV) of needle biopsy was evaluated in comparison with surgical pathology in patients who underwent surgical excision of the tumors.
RESULTS: Serial radiologic exams were available for growth rate measurement in 31 tumors (size 0.7-9.1 cm) from 25 patients. Among these, 24 tumors increased in size, and 7 were stable. The median follow-up duration was 23.5 months [interquartile range (IQR) 14.8-51.9], and the tumor growth rate ranged from - 0.36 to 2.26 cm per year (median 0.26, IQR 0.07-0.44). Needle biopsy results were available for comparison with postoperative pathology specimens in 147 patients. The PPV was 97.7% for fine-needle aspiration biopsy and 100% for core-needle biopsy. There were no reports of inflammation, facial nerve paralysis, or admission event during the follow-up.
CONCLUSIONS: WT glows slowly and can be predicted by needle biopsy. Therefore, parotid masses diagnosed as Warthin's tumor can be treated or left untreated based on the patient's needs and clinical decision-making.

Xie C, Du LY, Guo F, et al.
Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration.
Mol Cell Biochem. 2019; 458(1-2):11-26 [PubMed] Related Publications
Dysregulation of microRNAs (miRNAs) has been found to disrupt the progression of oral cancer. However, which miRNAs are most effective against oral cancer and how these miRNAs should be delivered are major unanswered problems. We aimed at investigating if human bone marrow mesenchymal stem cells (hBMSCs)-derived exosomes affect oral cancer development, and the potential regulatory mechanism associated with COL10A1 and miR-101-3p. COL10A1 was upregulated, while miR-101-3p was downregulated in oral cancer, and miR-101-3p targeted COL10A1 as verified by dual-luciferase reporter gene assay. Meanwhile, exosomes derived from hBMSCs were isolated and then co-cultured with oral cancer cells to identify the role of exosomes, and the results suggested that hBMSCs-derived exosomes overexpressing miR-101-3p inhibited oral cancer progression. Furthermore, tumorigenicity assay in nude mice further confirmed the inhibitory effects of hBMSCs-derived exosomes, loaded with miR-101-3p, on oral cancer, which provides a new theoretical basis in the treatment of oral cancer.

Kavabata NK, Caly DN, Ching TH, et al.
Predictive factors for late cervical metastasis in stage I and II squamous cell carcinoma of the lip.
Eur Arch Otorhinolaryngol. 2019; 276(7):2047-2053 [PubMed] Related Publications
PURPOSE: Many authors have described clinicopathologic parameters as factors related to cervical lymph node metastasis development in
METHODS: A multi-institutional study with 193 consecutive patients with early lip SCC treated from January 1990 to March 2006 was carried out retrospectively to determine factors predicting occult metastasis.
RESULTS: The overall late LNM rate was 13% (25/193). In the multivariate logistic regression study, tumour size and pattern of tumour invasion were factors related to the occurrence of late LNM with rates of sensitivity, specifity and accuracy for occult LNM prediction of 50%, 89.5% and 87%, respectively.
CONCLUSION: Our results indicate that patients with stage I and II SCC of the lip with tumour size greater than 18 mm and more aggressive pattern of invasion must be considered a high-risk group for LNM and an END should be performed.

Qi F, Sun Y, Lv M, et al.
Effects of palmatine hydrochloride mediated photodynamic therapy on oral squamous cell carcinoma.
Photochem Photobiol Sci. 2019; 18(6):1596-1605 [PubMed] Related Publications
Oral squamous cell carcinoma (OSCC) is a common malignant tumor, accounting for about 7% of all malignant tumors. Palmatine hydrochloride (PaH) is the alkaloid constituent of Fibraurea tinctoria Lour. The present study aims to investigate the antitumor effect of photodynamic therapy (PDT) with PaH (PaH-PDT) on human OSCC cell lines both in vitro and in vivo. The results indicate that PaH-PDT exhibited a potent phototoxic effect in cell proliferation and produced cell apoptosis. PaH-PDT increased the percentage of cells in the G0/G1 phase and decreased the CDK2 and Cyclin E1 protein level. In addition, PaH-PDT markedly increased the generation of intracellular ROS, which can be suppressed using the ROS scavenger N-acetylcysteine (NAC). Furthermore, PaH-PDT increased the expression of p53 protein in vitro and in vivo. In vivo experiments revealed that the PaH-PDT resulted in an effective inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. Moreover, no obvious signs of side effects or a drop in body weight was observed. These results suggested that PaH was a promising sensitizer that can be combined with light to produce significant anti-tumor effects in oral squamous cell carcinoma via enhanced ROS production and up-regulated expression of p53.

Li C, Chen Q, Tian Z, et al.
Expression of MIF, Beclin1, and LC3 in human salivary gland adenoid cystic carcinoma and its prognostic value.
Medicine (Baltimore). 2019; 98(20):e15402 [PubMed] Free Access to Full Article Related Publications
Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy with a poor long-term prognosis. Clinical reports show the high rates of local recurrences and distant metastases. This study aimed to investigate the expression of MIF, Beclin1, and light-chain 3 (LC3) in salivary adenoid cystic carcinoma (SACC).Tissue specimens were obtained from 48 salivary glands adenoid cystic carcinoma (SACC) patients and 15 oral squamous cell carcinoma (OSCC) patients. Immunohistochemical staining was performed to estimate the level of LC3, Beclin1, and MIF. All SACC patients were followed up. The Kaplan-Meier method was used to compare the prognosis of patients after treatment.The 3-year, 5 year-, and 10 year-survival rates of the SACC patients were 83.9%, 69.9%, and 46.6%, respectively. MIF, LC3, and Beclin1 in SACC were all obviously over-expressed. MIF showed an increased tendency in cases with advanced TNM stages, and at the same time, there was an inversely proportional relationship between MIF and LC3, Beclin1.The long-term survival of SACC patients is poor. MIF might be a risk factor for SACC patients, whereas, LC3 and Beclin1 might be an effective strategy for treatment of SACC.

Loree JT, Popat SR, Burke MS, et al.
Sentinel lymph node biopsy for management of the N0 neck in oral cavity squamous cell carcinoma.
J Surg Oncol. 2019; 120(2):101-108 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The management of the clinically N0 (cN0) neck is controversial for early stage squamous cell carcinoma of the oral cavity (OSCC). This paper represents a single institution series analyzing the efficacy of sentinel lymph node biopsy (SNB) for early stage oral cavity cancers.
METHODS: From 2005 to 2017, 108 patients with cN0 OSCC were treated with primary resection and SNB. Patients with positive biopsy results proceeded to neck dissection with or without adjuvant chemoradiotherapy. Mean follow-up for the entire cohort was 50.8 months (range: 8-147 months). Clinically, 56 patients were T1N0, 49 patients were T2N0, and three patients were T3N0 or greater.
RESULTS: Disease-specific survival was 93% within the entire cohort. Sentinel lymph nodes were identified in 95.4% of patients. Twenty one patients had a positive biopsy. There were seven false-negative biopsies. The overall rate of nodal disease was 26%. Accuracy of node biopsy was 93%, with sensitivity of 75%, and negative predictive value of 91%. Recurrence rate was 19% (20/108), with an overall survival of 60% in this subgroup.
CONCLUSION: SNB is a safe, effective, and well tolerated method for staging cN0 OSCC.

Jehn P, Dittmann J, Zimmerer R, et al.
Survival Rates According to Tumour Location in Patients With Surgically Treated Oral and Oropharyngeal Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(5):2527-2533 [PubMed] Related Publications
BACKGROUND/AIM: We evaluated survival rates in surgically-treated oral and oropharyngeal squamous cell carcinoma patients at our clinic, and determined whether survival differed by tumour locations.
PATIENTS AND METHODS: In a retrospective study, tumour lesions in 1,486 patients were categorized into 6 groups according to tumour location. Patients' age, sex, tumour-node-metastasis classification, resection status, 5-year and disease-specific survival rates were statistically analysed between groups.
RESULTS: A significantly inferior disease-specific and lower 5-year survival rates for tumours located at the base of the tongue and oropharynx, and maxilla, due to higher T-stage and incomplete resection status were shown. Cervical lymph node metastasis and distant metastatic spread were more frequently observed with base of the tongue and oropharynx lesions.
CONCLUSION: Attentive inspection and precise clinical examinations of specific oral and oropharyngeal regions are crucial for early diagnosis and treatment. Oral and oropharyngeal tumour locations play important roles in disease prognosis.

Morikawa T, Kosugi A, Shibahara T
The Utility of Optical Instrument "ORALOOK®" in the Early Detection of High-risk Oral Mucosal Lesions.
Anticancer Res. 2019; 39(5):2519-2525 [PubMed] Related Publications
BACKGROUND/AIM: Oral cancer screening is important for early detection and early treatment, which help improve survival rates. Biopsy is invasive and painful, while fluorescence visualization is non-invasive, convenient, and real-time, and examinations can be repeated using optical instruments. The purpose of this study was to clarify the usefulness of an optical instrument in oral screening.
PATIENTS AND METHODS: A total of 201 patients, who were examined using an optical instrument in our Department between 2017 and 2018, were enrolled in this study. Fluorescence visualization images were analyzed using subjective and objective evaluations.
RESULTS: Subjective evaluations for detecting oral cancer and oral epithelial dysplasia offered 83.3% sensitivity and 75.7% specificity. Regarding the objective evaluations for detecting oral cancer and oral epithelial dysplasia, sensitivity and specificity were 47.4% and 72.4% for luminance value, 94.7% and 79.6% for luminance ratio, and 100.0% and 68.0% coefficient of variation.
CONCLUSION: Fluorescence visualization using optical instruments is useful for oral cancer screening.

Antunes DM, Rodrigues MFSD, Guimarães DM, et al.
Nonsteroidal Anti-inflammatory Drugs Modulate Gene Expression of Inflammatory Mediators in Oral Squamous Cell Carcinoma.
Anticancer Res. 2019; 39(5):2385-2394 [PubMed] Related Publications
BACKGROUND: Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines.
MATERIALS AND METHODS: Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction.
RESULTS: Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib.
CONCLUSION: Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.

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