Squamous Cell Carcinoma Presenting as Pericoronitis: Implications of Delayed Diagnosis

Swallowing outcomes following primary surgical resection and primary free flap reconstruction for oral and oropharyngeal squamous cell carcinomas: a systematic review protocol

MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma in tissue and plasma

PurposeThe aim of the study is to investigate the immunohistochemical expression of both Alpha smooth muscle actin and Transforming Growth Factor beta and compare their expression in oral papillary squamous cell carcinoma with their expression in different histological grades of oral squamous cell carcinoma. A correlation between these immuno-histochemical expressions and histological findings will then be performed. The research question is “Do the percentages of α-SMA and TGF-β immune-expression in OPSCC differ from that in the conventional OSCC?”.MethodsThis will be achieved by collecting archival blocks of oral papillary squamous cell carcinoma and different grades of oral squamous cell carcinoma, staining the specimens with Transforming Growth Factor beta and alpha smooth muscle actin, then measuring the mean staining index of expression in each group and the area percent of both markers.ResultsResults revealed that transforming growth factor beta expression in the epithelium was high in all cases of well-differentiated squamous cell carcinoma, most oral papillary squamous cell carcinoma, and poorly differentiated oral squamous cell carcinoma. On the other hand, different grades of oral squamous cell carcinoma showed a high staining index of alpha smooth muscle actin expression in the stroma. While cases of oral papillary squamous cell carcinoma were either moderate or low-staining.ConclusionsOral papillary squamous cell carcinoma has a favourable prognosis compared to different histological grades, and the prognosis does not depend only on histological grade but also on other prognostic factors.

Simple SummaryThe treatment of oral squamous cell carcinoma (OSCC) represents a significant problem worldwide. Among cancers with the highest incidence, OSCC renders one of the worst prognoses. Therefore, novel prognostic biomarkers and therapeutic tools to tackle OSCC are urgently needed. Somatostatin-analogues (SSA) are an invaluable therapeutic option in the treatment of several cancers. We aimed to determine the expression levels of all somatostatin-receptors (SSTs) in OSCC, compared to adjacent healthy control tissues, to analyze the relationship of SSTs expression with key clinical and histopathological data, and to explore the direct in vitro effect of different SSAs on OSCC cancer cells. Our findings highlight a potential role of SST2 as a good prognostic biomarker for recurrence and metastasis in OSCC and unveil that SSA exerts antitumoral effects on OSCC cells, providing a relevant clinical conclusion, which should be soon tested for their use in humans.Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.

Background:Oral mucositis is a serious complication radiation therapy for cancer. This is a major complication during radiation therapy of the head and neck tumors in approximately all patients. Therefore, this study was conducted to evaluate the effect of Mucosamin on treatment of radiation induced oral mucositis during and after radiotherapy amongst patients with oral cavity squamous cell carcinoma. Materials and Methods:In this prospective clinical trial, eligible patients who referred to radiation oncology department of Namazi Hospital, Shiraz, Iran from Jan 2018 till Jan 2019 were evaluated. The cases with confirmed pathologic diagnosis of squamous cell carcinoma of the oral cavity underwent 6,000 cGy radiation therapy and were randomly divided into two groups: 1- Intervention group; Mucosamin spray for 3-4 times a day (n = 40); 2 - Control group; standard medications (3 times a day) (n = 40). Oral mucositis was evaluated weekly based on RTOG scoring scale. Grade of mucositis was recorded during treatment and after radiation therapy. Results:A total of 80 patients were divided in two groups of Mucosamin and control. From week 3 until the end of radiotherapy (week 6) and after radiotherapy (week 8), there was a significant difference in the severity of oral mucositis between the Mucosamin and the control groups (P <0.05). Conclusion:The results of this study showed that Mucosamin spray was able to significantly improved radiation-induced oral mucositis in patients with oral squamous cell carcinoma.

Environmental exposure to carcinogens causes mucosal damage in the upper aerodigestive tract, which can lead to cancers. The genetic basis of head and neck cancer is controversial. To identify susceptibility genes in head and neck cancers, we enrolled patients with early-onset disease in Taiwan. This case-control study included 54 young male patients with oral squamous cell carcinoma (OSCC) who were treated between March 1996 and December 2016, as well as 2,400 healthy controls. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OSCC. Sequencing-based typing (TBG Biotechnology Corp., Taipei, Taiwan) was used to determine the HLA-DQB1 genotype in another cohort of 147 OSCC patients. We analyzed the allele frequencies of 664,994 autosomal SNPs in the 54 OSCC cases. In a genome-wide association analysis, four SNPs within loci on chromosomes 6, 7, 9, and 12 were significantly different between OSCC patients and controls (corrected P &amp;lt; 1.0 × 10−6). HLA-DQB1 was closest to rs28451423 on chromosome 6. HLA-DQB1*05:02 in OSCC (18.5%) was significantly different from normal population (7.0%) (P = 0.009). The influence of disease onset was independently significant after adjusting cigarette smoking, alcohol drinking and areca-quid chewing (P = 0.015, OR: 3.922, 95% confidence interval: 1.311 - 11.734). Furthermore, HLA-DQB1*05:02 was associated with early-onset OSCC (P = 0.004). HLA-DQB1*05:02 is associated with OSCC independent of environmental exposures. HLA-DQB1*05:02 is also related with early onset of OSCC. It provides evidence of a genetic basis for OSCC. Citation Format: Shiang-Fu Huang, Huei-Tzu Chien, Chi-Kuan Young, Yun-Shien Lee, Chun-Ta Liao, Kai-Lun Cho, Ching-Han Chen. HLA-DQB1*05:02: An independent genetic marker for oral cavity squamous cell carcinoma susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB379.

Nerve Growth Factor and Tyrosine Kinase A Receptor in Oral Squamous Cell Carcinoma: Is There an Association With Perineural Invasion?

This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.

Oral squamous cell carcinoma positive for p16/human papilloma virus in post allogeneic stem cell transplantation: 2 cases and review of the literature

The specific function of phosphatidylserine (PS) in the context of the development of a hypercoagulable state among individuals with oral squamous cell carcinoma (OSCC) is uncertain. The goal of this study was therefore to assess the exposure of PS on microparticles (MPs) as well as on endothelial and blood cells and to assess procoagulant activity (PCA) as a function of the stage of OSCC progression. We recruited patients with OSCC (n = 63) as well as healthy controls (n = 26) to participate in this study. PS exposure was then assessed via confocal microscopy and flow cytometry, revealing that patients with stage III/IV OSCC exhibited higher frequencies of PS-exposing blood cells, MPs, and serum-cultured endothelial cells (ECs) than did patients with stage I/II OSCC or healthy controls. When we conducted functional coagulation assays, we discovered that PS+ blood cells, MPs, and serum-cultured ECs from patients with stage III/IV OSCC mediated more rapid coagulation and more substantial production of FXa, thrombin, and fibrin as compared with controls. When samples were treated with the PS antagonist lactadherin, this resulted in an 80% disruption of PCA. Strikingly, when pre- and postoperative samples were compared from patients with stage III/IV OSCC undergoing resective surgery, PCA was significantly reduced in the postoperative samples. After stimulating ECs with inflammatory cytokines, we found by confocal microscopy that they expose PS on their cell membranes, thus generating FVa and FXa binding sites and mediating the formation of fibrin. Together our findings provide evidence that PS+ blood cells and MPs are important mediators of the development of a hypercoagulable and prothrombotic state among individuals afflicted by advanced-stage OSCC. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

Background: Metastasis of aerodigestive tract cancers to cervical lymph nodes is one of the otolaryngologists’ concerns that relies on a variety of factors such as the size of the primary tumor and its spread. We aimed to study the prevalence of occult cervical metastases in patients with clinical N0 neck in oral cavity squamous cell carcinoma. Methods: In this cross-sectional analytic study, the researchers referred to the archive of Emam Reza Hospital and studied medical files of patients with a definite diagnosis of oral cavity squamous cell carcinoma admitted from April 2011 to April 2016 while collecting relevant data such as age, gender, size of the primary mass, place of the lesion, clinical and pathological nodal involvement. The data was analyzed employing SPSS 19 whereas the statistical significance level in all exams was set at 0.05. Results: Average age of participants was 61.67 ± 14.02, and they were mostly male. Forty-five percent of participants had a clinical N0 neck and the majority of them didn’t have metastasis in the pathological study. The prevalence of metastatic lymph nodes in patients with clinical N0 was 30%. No significant relationship was observed between the number of lymph nodes containing occult metastasis and T of the tumor (P = .578). Conclusion: In squamous cell carcinoma of oral cavity, the prevalence of metastatic lymph nodes in the neck is 30% and is significantly related to the location of the lesion while no significant relationship to T of the tumor is observed.

This study assessed the efficacy of using oral liquid-based brush cytology and cell block immunocytochemistry in the diagnosis of oral leukoplakia as minimally invasive diagnostic adjuncts. Seventy-two patients diagnosed clinically with either oral leukoplakia (OLK) or oral squamous cell carcinoma were included. Oral brush samples using Orcellex® brushes were obtained from all participants directly before undergoing surgical biopsy. Cell blocks were prepared for all samples and assessed for cytomorphology and immunocytochemistry of DNA mismatch repair proteins (MSH-6, MSH-2, MLH-1 and PMS-2). A combined index score of immunocytochemistry expression and cytology grading was compared against the gold standard (histopathological diagnosis). A significant association was observed between the cytological assessments of oral liquid-based brush cytology samples and the histopathological diagnosis (P<.005). In addition, there was a significant inverse correlation between the grade of oral epithelial dysplasia and the cumulative score of the studied DNA mismatch repair proteins (P<.005). Grading criteria for both oral liquid-based brush cytology and immunocytochemistry cumulative index scores are proposed based on the analysis of receiver operating characteristic curve coordinates. The diagnostic accuracy of this approach was outstanding in terms of discrimination between the presence or absence of oral epithelial dysplasia (0.961) and squamous cell carcinoma (0.977) separately. Oral liquid-based brush cytology cell block immunocytochemistry provides a reliable strategy to investigate oral mucosal epithelial disorders. This approach presents a minimally invasive, highly accurate and non-technically demanding method for the surveillance of oral potentially malignant disorders and squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers

The prognosis of human malignancies has been shown to depend on immunological parameters, such as macrophage polarization (M1 and M2). In this study, we identify the phenotype of macrophages, and investigate an involvement of infiltrated T cells that participate in the polarization of macrophages, in oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC). Immunohistochemical method was used to examine the number of CD68+ , CD163+ (M2), iNOS+ (M1) macrophages, and CD4+ , CD8+ , CCR4+ (Th2), CCR5+ (Th1) cells in 102 cases of OSCC: without metastases-OSCC M(-) (n = 54), and with metastases-OSCC M(+) (n = 48), 23 cases of OLK, and 18 control cases. The mean number of CD68+ , CD163+ , iNOS+ , CD4+ , CCR4+ , CCR5+ cells was significantly increased in OSCC M(+) group compared with OLK, OSCC M(-) and control group. We found positive correlations between the number of CD4+ T cells and CD163+ and iNOS+ macrophages as well as CCR4+ and CCR5+ cells in both OSCC groups. The mean number of CD8+ cells was significantly increased in OSCC M(-) and OLK compared with OSCC M(+) and control group. In OSCC M(+) and OSCC M(-) groups, a negative correlation between the number of CD8+ cells and CD163+ and iNOS+ macrophages was found. The number and co-localization of lymphocytes and macrophages in OLK and OSCC may indicate that infiltrating cells influence the early and subsequent stage of oral carcinogenesis.