Oral Cavity Squamous Cell Carcinoma Research Articles

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery. A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: midepithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, and cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing midepithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), whereas 40 of 79 p53-abnormal cases had positive lymph nodes (P < .001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; P = .008).p53-Abnormal OSCCs were significantly more likely to be associated with positive lymph node status than p53 wild-type OSCCs at the time of surgery. Further investigation with long-term follow-up is required to determine its clinical application before surgery planning.

917P Automatic characterization of spatial arrangement of tumor-infiltrating lymphocytes identifies oral cavity squamous cell carcinoma patients with poorer prognosis

917P Automatic characterization of spatial arrangement of tumor-infiltrating lymphocytes identifies oral cavity squamous cell carcinoma patients with poorer prognosis

Clinicopathological Factors Associated with Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma: A Retrospective Analysis

Abstract Background: Metastasis to regional cervical lymph nodes is an important prognostic factor for oral-cavity squamous cell carcinomas (OSCC). However, it is difficult to predict nodal metastasis in OSCC. The current study was done with an aim to find the association of various clinicopathological factors to the presence of cervical lymph node metastasis in OSCC. Materials and Methods: A retrospective analysis of hospital records from January 2020 to June 2023 was conducted in a tertiary care center. The records of 65 patients were included as per the inclusion criteria. The data were divided into two groups based on the presence or absence of neck nodal metastasis. Various factors such as tumor size, volume, depth of invasion (DOI), lymphovascular invasion, and perineural invasion were statistically compared between the study groups. Results: The oral tongue was the most common subsite (25, 38.5%), followed by buccal mucosa (18, 27.7%). The mean DOI in the group with cervical lymph node metastasis was 9.83 ± 4.83 mm, and it was significantly higher than the group without cervical lymph node metastasis (6.15 ± 4.20 mm, P = 0.004). Conclusion: DOI assessment is one of the most important preoperative assessments in the clinicoradiological assessment of OSCC cases. Further, it is recommended that in cases with DOI &gt;5 mm, the intraoperative frozen section on the nodes dissected in elective neck dissection is done for further determination of the extent of neck dissection.

A Multimodal Protocol Combining 99mTc-Tilmanocept with Indocyanine Green Fluorescence Lympho-Angiography for Sentinel Lymph Node Biopsy in Early-Stage Oral Cancer: A Case Series.

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called "shine-through radioactivity" of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining 99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with 99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical "roadmap". In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted.

Integrated Single-cell and Bulk RNA Sequencing Analysis Cross Talk between Ferroptosis-related Genes and Prognosis in Oral Cavity Squamous Cell Carcinoma.

Ferroptosis is a new type of programmed apoptosis and plays an important role in tumour inhibition and immunotherapy. In this study, we aimed to explore the potential role of ferroptosis-related genes (FRGs) and the potential therapeutic targets in oral cavity squamous cell carcinoma (OCSCC). The transcription data of OCSCC samples were obtained from the Cancer Genome Atlas (TCGA) database as a training dataset. The prognostic FRGs were extracted by univariate Cox regression analysis. Then, we constructed a prognostic model using the least absolute shrinkage and selection operator (LASSO) and Cox analysis to determine the independent prognosis FRGs. Based on this model, risk scores were calculated for the OCSCC samples. The model's capability was further evaluated by the receiver operating characteristic curve (ROC). Then, we used the GSE41613 dataset as an external validation cohort to confirm the model's predictive capability. Next, the immune infiltration and somatic mutation analysis were applied. Lastly, single-cell transcriptomic analysis was used to identify the key cells. A total of 12 prognostic FRGs were identified. Eventually, 6 FRGs were screened as independent predictors and a prognostic model was constructed in the training dataset, which significantly stratified OCSCC samples into high-risk and low-risk groups based on overall survival. The external validation of the model using the GSE41613 dataset demonstrated a satisfactory predictive capability for the prognosis of OCSCC. Further analysis revealed that patients in the highrisk group had distinct immune infiltration and somatic mutation patterns from low-risk patients. Mast cell infiltrations were identified as prognostic immune cells and played a role in OCSCC partly through ferroptosis. We successfully constructed a novel 6 FRGs model and identified a prognostic immune cell, which can serve to predict clinical prognoses for OCSCC. Ferroptosis may be a new direction for immunotherapy of OCSCC.

Patterns of lymph node involvement for oral cavity squamous cell carcinoma

AimWhereas the prevalence of lymph node level (LNL) involvement in oral cavity squamous cell carcinomas (OCSCC) has been reported, the details of lymphatic progression patterns are insufficiently quantified. We investigate how the risk of metastases in each LNL depends on the involvement of adjacent LNLs, T-category, subsite, primary tumor lateralization, and other risk factors. MethodsWe retrospectively analyzed patients with newly diagnosed OCSCC from two institutions, totaling 348 patients. Involvement of LNLs I-V was recorded individually based on pathology after neck dissection with clinicopathological factors. The dataset is publicly available in a previously developed web-app, which allows querying patients with specific combinations of co-involved LNLs and tumor characteristics. ResultsIpsilateral involvement prevalence of levels I-III was higher for advanced T-category (T3/T4) patients (32 %, 38 %, 14 %) compared to early (T1/T2) patients (14 %, 23 %, 11 %). Involvement of level I increased the involvement probability in levels II and III. Similarly, involvement of level II increased the involvement probability in levels I and III. However, there was significant isolated involvement of level I or II. Advanced nodal involvement (>1 LNL involved) was more frequent for patients with extracapsular extension. Overall contralateral involvement in levels I-III was 7 %, 4 %, 3 % and more frequent for more advanced ipsilateral involvement and for midline-crossing tumors. Involvement of levels IV and V was rare: 3 % ipsilateral and 1 % contralateral in both levels. ConclusionsDetailed quantification of LNL involvement in OCSCC depending on involvement of adjacent LNLs and clinicopathological factors may allow further personalizing guidelines on elective nodal treatment.

The Role of the Pre-surgical Biopsy of Oral Cavity Squamous Cell Carcinoma

The Role of the Pre-surgical Biopsy of Oral Cavity Squamous Cell Carcinoma

199 Comparing survival and recurrence patterns in locally advanced oral cavity squamous cell carcinoma

199 Comparing survival and recurrence patterns in locally advanced oral cavity squamous cell carcinoma

Loss of Independence in Older Adults With Operable Oral Cavity Cancer: A Retrospective Cohort Study.

To ascertain the effect of curative-intent surgery on loss of independence (LOI) in patients with oral cavity squamous cell carcinoma (OCSCC). Retrospective observational study of patients diagnosed from 2014 to 2021. Single tertiary care academic center. Patients having undergone curative-intent surgical treatment for OCSCC from 2014 to 2021 in the cancer registry. LOI as the primary outcome was measured based on a combination of decrease in activities of daily living (ADLs) and/or decline in mobility during treatment. Descriptive statistics were used to compare baseline demographics and multivariable logistic regression was used to assess the association between LOI and perioperative variables of interest. Of the 180 patients included in this study, 139 (79%) were fully independent in ADLs/instrumental ADLs prior to surgery. The average age of the cohort was 74 with 49% males. Thirty-seven(21%) experienced a decline in mobility or increased care needs following surgery, and 18 (10%) experienced an independent decline in functional status. Increasing age, osseous flap reconstruction, high Charlson Comorbidity Index, and major postoperative adverse events were associated with LOI. Fifty-five percentof patients with LOI had recovered to baseline within 7 months from surgery. LOI was associated with poor treatment tolerance (odds ratio: 4.77, 95% confidence interval: 1.87-12.2) while adjusting for multiple confounders. LOI is common in older adults undergoing curative-intent surgery for OCSCC and associated with poor treatment tolerance.

Is Dental Specialty Referral Associated With Earlier Presentation of Oral Cavity Squamous Cell Carcinoma?

BackgroundOral cavity squamous cell carcinoma (OSCC) may mimic other more common odontogenic processes such as infection, trauma, and benign pathology. Delays in diagnosis and treatment are known to result in poorer survival outcomes. PurposeThe study purpose was to measure the association between referral type and OSCC stage at time of presentation.Study design, setting, sample: This was a retrospective cohort study composed of newly diagnosed OSCC patients treated with surgical resection from 2014 to 2023 at Roswell Park Comprehensive Cancer Center (RPCCC). Patients who presented with self-referrals or had surgical treatment outside of RPCCC were excluded. PredictorThe primary predictor was referral source (dental versus medical specialty). Main outcome variableThe primary outcome was pathological T stage (pT). The secondary outcome was overall survival (OS). CovariatesCovariates included demographic data and cancer-related variables (symptomatology, subsite, and risk factors). AnalysesA multivariate logistical regression model for pT stage was constructed using all significant covariates as well as preoperative patient and tumor characteristics. For OS, Kaplan-Meier survival curves were constructed and compared with the log-rank test. A p<0.05 was considered statistically significant. ResultsA total of 215 subjects were included in the study sample. The majority were referred by a dental provider (n=132, 62.3%). Dental referrals presented with significantly earlier T stage disease (RRpT3/T4 0.65, p<0.01) and had lower rates of cervical nodal positivity (RRpN1-N3 0.62, p=0.01). Dental referral independently increased the odds of early pT stage presentation (OR 5.10, p<0.01) after controlling for age, sex, oral pain symptoms, social history (smoking and drinking), head neck cancer history, and tumor subsite. Dental referrals had significantly improved OS (p=0.03) and were also associated with lower rates of oral pain symptoms (RRoral pain 0.80, p=0.02), LVI (RRLVI 0.50 ; p=0.04), and PNI (RRPNI 0.63, p=0.04). ConclusionsAmong subjects with similar risk factors, those referred from dental providers were found to have earlier stage disease. Unfortunately, over half of dental referrals still presented with pain symptoms and more than a third presented with locally advanced disease. Dental providers appear to be positioned to detect earlier OSCC, however there is room for improvement.

355 Evaluation of Extent of ENE AND PNI on Survival Outcomes in Oral Cavity SCC Treated with Adjuvant RT

355 Evaluation of Extent of ENE AND PNI on Survival Outcomes in Oral Cavity SCC Treated with Adjuvant RT

Prognostic value of pretreatment temporal muscle thickness after curative surgery for oral cavity squamous cell carcinoma.

Sarcopenia is a poor prognostic factor in various diseases. Temporal muscle thickness (TMT) has been reported to be associated with sarcopenia. We investigated the prognostic value of TMT in patients with oral squamous cell carcinoma. This study included 61 patients with oral squamous cell carcinoma. Two board-certified otolaryngologists measured TMT based on pre-treatment CT. The following sex-specific TMT cut-off values were used in accordance with previous reports: ≤ 6.3mm in men, and ≤ 5.2mm in women. We classified patients into normal TMT group and low TMT group according to the cutoff values. The correlation between the TMT measurements of the two readers was tested using the interclass correlation coefficient (ICC). Cox regression models were used to verify the association between TMT and prognostic factors. The low TMT group had a significantly lower BMI than the normal TMT group. Patients with low TMT at baseline had a significantly higher risk of death than those with normal TMT (hazard ratio 4.51; 95% confidence interval [CI] 1.49-13.61; p = 0.0076). There were no significant differences in disease-specific survival between the two groups. The correlation between the two evaluators' TMT measurements was excellent (ICC 0.988, 95% CI 0.981-0.933). Sex-specific TMT was associated with overall survival in patients with oral squamous cell carcinoma. TMT is easy to assess and its measurement is consistent between evaluators.

Immune cell topography of head and neck cancer

BackgroundApproximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are treatment options for recurrent/metastatic HNSCC; however, less than 20% of...

Soluble CD44 in oral rinses for the early detection of cancer: a prospective cohort study in high-risk individuals

BackgroundThere are 54,000 new cases of oral cavity and oropharyngeal cancer in the United States and more than 476,000 worldwide each year. Oral cavity and oropharyngeal squamous cell carcinoma make up most tumors with five-year survival rates of 50% due to prevalence of late-stage diagnoses. Improved methods of early detection in high-risk individuals are urgently needed. We aimed to assess the tumorigenic biomarkers soluble CD44 (solCD44) and total protein (TP) measured using oral rinses as affordable convenient screening tools for cancer detection.MethodsIn this prospective cohort study, we recruited 150 healthy current or former smokers through a community screening program. Baseline and four annual visits were conducted from March 2011-January 2016 with records followed until August 2020. Participants provided oral rinses, received head and neck exams, and completed questionnaires. SolCD44 and TP levels were measured and compared across groups and time. Participants were placed in the cancer group if malignancy developed in the study period, the suspicious group if physical exams were concerning for premalignant disease or cancer in the head and neck, and the healthy group if there were no suspicious findings. This analysis used two-sample t-test for comparison of means and two-sample Wilcoxon Test for comparison of medians. For subjects with follow-ups, estimated means of biomarkers were obtained from a fitted Repeated Measures Analysis of Variance (RANOVA) model including group, visit, and their interaction. Pairwise comparisons of mean solCD44 were made, including intergroup and intragroup comparison of values at different years.ResultsMost participants were males (58.7%), < 60 years of age. (90.7%), and Black (100%). Baseline mean solCD44 was elevated (2.781 ng/ml) in the cancer group compared to the suspicious group (1.849 ng/ml) and healthy group (1.779 ng/ml).ConclusionThis study supports the feasibility of a CD44-based oral rinse test as an affordable and convenient adjunctive tool for early detection of aerodigestive tract and other cancers in high-risk populations.

Analysis of the Ki-67 Proliferation Index in Relation to Tumor, Node, and Metastasis (TNM) Stage in Patients With Oral Cavity Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) comprises more than 90% of malignant tumors of the oral cavity, accounting for up to 40% of all malignancies in South Asia. Despite the progress made in cancer management, the five-year survival rate for SCC has remained around 50%. To improve this survival rate, it is essential to understand the tumor's biology at its core. In our study, the Ki-67 proliferation index of tumor cells was analyzed and correlated with the tumor stage, nodal stage, and tumor grade to determine the tumor's biological aggressiveness. Materials and methods The study was conducted in a tertiary care center in South Asia from 2018 to 2022. A total of 50 adult patients with biopsy-proven oral cavity SCC were taken for analysis. The Ki-67 index was assessed in tumor cells using immunohistochemistry. Results Ki-67 was classified into two subcategories: <20% and >20%. Patients with an advanced T stage (T3-T4) have a greater chance of having a higher Ki-67 index (>20%), with p = 0.047. However, there is no statistically significant association between nodal status and tumor grade. Conclusion The Ki-67 proliferation index predicts the behavior of SCC lesions regarding tumor size and invasiveness.

Architectural dysplasia in surgical margins and the risk of local relapse in oral cancer.

A major challenge in the clinical management of oral cavity squamous cell carcinoma is local relapse. Even when surgical margins are tumor-free, local relapses occur frequently, and relapse prediction by histology remains suboptimal. In leukoplakia, an oral potentially malignant disorder, the presence of architectural dysplasia is a critical risk factor for malignant transformation. This study aimed to investigate whether the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is a risk factor for local relapse. Hematoxylin and eosin-stained slides of resection margins from a consecutive cohort of surgically treated patients diagnosed with stage I-IV oral cavity squamous cell carcinoma between 2008 and 2014 were assessed for the presence of architectural dysplasia (N = 311). Five-year local relapse-free survival rates of oral cavity squamous cell carcinoma with architectural dysplasia were compared to those of oral cavity squamous cell carcinoma without architectural dysplasia. In total, 92 of 311 (29.6%) of oral cavity squamous cell carcinoma displayed architectural dysplasia in the margins. The presence of architectural dysplasia was associated with higher patient age, female sex, less pack years, lower cT-stage, and a cohesive tumor growth pattern. In oral cavity squamous cell carcinomas with architectural dysplasia, postoperative (chemo)radiotherapy was less often indicated compared with oral cavity squamous cell carcinoma without architectural dysplasia (19.5% vs. 36.1%, p = 0.009). Five-year local relapse-free survival was significantly lower in oral cavity squamous cell carcinoma with architectural dysplasia than in oral cavity squamous cell carcinoma without architectural dysplasia (83.1% vs. 94.9%, p = 0.017). Oral cavity squamous cell carcinoma arising in the background of architectural dysplasia displays relatively favorable clinical and histopathological characteristics. Nonetheless, the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is associated with a higher risk of local relapse, indicating its clinical relevance.

Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4- mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFβ signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Multicriteria optimization of radiation therapy: Towards empowerment and standardization of reverse planning for head and neck squamous cell carcinoma

PurposeThe purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers. Material and methodsWe performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method. ResultsMedian age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was −2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was −4.6Gy (P<0.001). ConclusionMulticriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

Prognostic Effectiveness of PD-L1 Tumoral Expression in Oral Cavity Squamous Cell Carcinoma

Prognostic Effectiveness of PD-L1 Tumoral Expression in Oral Cavity Squamous Cell Carcinoma

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.