Invasive Squamous Cell Carcinoma Research Articles

Expression of Ubiquitin C-Terminal Hydrolase-L1 in Minor Normal Salivary Gland Tissues in Perilesional Area to OSCC

Ubiquitin C-terminal hydrolase L1 (UCH-L1), is a deubiquitinating enzyme. Certain changes in ubiquitination attribute to uncontrolled growth, leading to oncogenesis. The aim of this study was to characterize UCH-L1 expression patterns in nor mal looking human minor salivary gland tissues in the perilesional area of oral squamous cell carcinoma (OSCC). A retrospective study in which UCH-L1 immunohistochemical staining performed for 27 formalin fixed paraffin embedded blocks of surgically removed primary OSCC containing perilesional minor salivary gland tissues. The expression, subcellular localization, pattern of distribution, and stain intensity were assessed. UCH-L1 was immunopositive in minor salivary gland tissues of all sections. The immunoreactivity was (70.4%) detected in the cytoplasm and (29.6%) as mixed expression (cytoplasm and nucleus). UCH-L1 was predominately expressed in the ductal system (40.7%), followed by the myoepithelial cells (33.35%), while it was weakly expressed in the acinar cells; mucous (14.9%) and serous acini (11.1%). UCH-L1 expression is detectable in minor salivary glands in a perilesional area of OSCC, Although previously approved that it was absolutely absent in normal salivary gland tissues, it may activate during the course of oncogenesis and can be classified as a marker for predicting the future invasion of OSCC to adjacent minor salivary gland tissues. This study provides evidence for additional studies on the UCH-L1 expression in normal salivary glands in patients with maxillofacial tumorigenesis.

Nivolumab for Patients With High-Risk Oral Leukoplakia

Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy. To determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL. This nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia). Patients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit. The primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response. A total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss. This immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study. ClinicalTrials.gov Identifier: NCT03692325.

Squamous Cell Carcinoma in Situ Achieves Tumor Clearance in More Mohs Stages Than Invasive Squamous Cell Carcinoma.

Squamous cell carcinoma in situ (SCCIS) has more subclinical lateral extension than invasive squamous cell carcinomas (SCC). To determine whether it takes a greater number of Mohs stages for clearance of SCCIS compared with SCC and whether the difference in final defect size and clinical size is larger in SCCIS than SCC. All Mohs micrographic surgery cases of SCCIS and SCC performed between January 2011 and December 2021 were identified. Number of Mohs stages were recorded and difference in final defect size and initial clinical size were calculated for SCCIS and SCC. 4,363 cases were included, 1,066 SCCIS and 3,297 invasive SCC. The initial clinical size, final defect size, and the size difference were similar between SCCIS and SCC groups. However, SCCIS underwent more Mohs stages to achieve tumor clearance than invasive SCCs (1.5 ± 0.7 vs 1.4 ± 0.7 respectively, p < .001). In fact, 71% of SCCs were cleared after 1 Mohs stage compared with 61.1% of SCCIS. These findings support that SCCIS has more subclinical lateral extension and therefore is appropriate for Mohs surgery.

Propofol inhibits the proliferation, invasion, migration, and angiogenesis of oral squamous cell carcinoma through circ_0008898-mediated pathway.

Propofol has been shown to inhibit oral squamous cell carcinoma (OSCC) progression. However, it is not clear whether propofol mediates OSCC progression through regulating circular RNA (circRNA) network. Quantitative real-time PCR was used to detect circ_0008898, miR-545-3p, and CT10 regulator of kinase-like protein (CRKL) expression. Cell functions were determined using CCK8 assay, Edu staining, MTT assay, transwell assay, wound healing assay, tube formation assay, and flow cytometry. Protein levels were examined by western blot analysis. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Our data showed that propofol repressed OSCC cell proliferation, invasion, migration, angiogenesis, and promoted apoptosis. circ_0008898 was highly expressed in OSCC, and its expression could be decreased by propofol. circ_0008898 silencing aggravated the suppressive effect of propofol on OSCC progression. In the mechanism, circ_0008898 could target miR-545-3p to positively regulate CRKL. MiR-545-3p inhibitor abolished the regulation of circ_0008898 silencing on propofol-mediated OSCC cell progression. MiR-545-3p inhibited the progression of propofol-treated OSCC cells, and this effect was reversed by CRKL overexpression. Also, circ_0008898 knockdown reduced OSCC tumor growth by regulating miR-545-3p/CRKL. In conclusion, propofol suppressed OSCC progression, which was achieved through regulating the circ_0008898/miR-545-3p/CRKL axis.

Development of Multiple Facial Lipomas During Immunotherapy for Metastatic Squamous Cell Carcinoma

An 85-year-old Caucasian male on immunotherapy for metastatic squamous cell carcinoma presented with enlarging lipomas in the area of his previous invasive squamous cell carcinoma of the lower lip and chin, status post resection, reconstruction and local radiation. The development of multiple lipomas during immunotherapy is a novel association which has yet to be reported in the literature. We discuss a putative mechanism of action of pembrolizumab-induced lipomas and describe the patient's clinical course.

USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-β-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

Preoperative Prediction of Perineural Invasion in Oesophageal Squamous Cell Carcinoma Based on CT Radiomics Nomogram: A Multicenter Study

To investigate the value of computed tomography (CT) radiomics nomogram in the preoperative prediction of perineural invasion (PNI) in oesophageal squamous cell carcinoma (ESCC) through a multicenter study. We retrospectively collected postoperative pathological data of 360 ESCC patients with definite PNI status (131 PNI-positive and 229 PNI-negative) from two centres. Radiomic features were extracted from the arterial-phase CT images, and the least absolute shrinkage and selection operator and logistic regression algorithm were used to screen valuable features for identifying the PNI status and calculating the radiomics score (Rad-score). A radiomics nomogram was established by integrating the Rad-score and clinical risk factors. A receiver operating characteristic curve was used to evaluate model performance, and decision curve analysis was used to evaluate the predictive performance of the radiomics nomogram in the training, internal validation, and external validation sets. Twenty radiomics features were extracted from a full-volume tumour region of interest to construct the model, and the radiomics nomogram combined with radiomics features and clinical risk factors was superior to the clinical and radiomics models in predicting the PNI status of ESCC patients. The area under the curve values of the radiomics nomogram in the training, internal validation, and external validation sets were 0.856 (0.794-0.918), 0.832 (0.742-0.922), and 0.803 (0.709-0.898), respectively. The radiomics nomogram based on CT has excellent predictive ability; it can non-invasively predict the preoperative PNI status of ESCC patients and provide a basis for preoperative decision-making.

Development and validation of a deep learning model for improving detection of nonmelanoma skin cancers treated with Mohs micrographic surgery

BackgroundReal-time review of frozen sections underpins the quality of Mohs surgery. There is an unmet need for low-cost techniques that can improve Mohs surgery by reliably corroborating cancerous regions of interest and surgical margin proximity. ObjectiveTo test that deep learning models can identify non-melanoma skin cancer (NMSC) regions in Mohs frozen section specimens. MethodsDeep learning models were developed on archival images of focused-microscopic views (FMV) containing regions of annotated, invasive NMSC between 2015 and 2018, then validated on prospectively collected images in a temporal cohort (2019-2021). ResultsThe tile-based classification models were derived using 1,423 FMV images from 154 patients and tested on 374 images from 66 patients. The best models detected basal cell carcinomas with a median average precision of 0.966 and median area under the receiver operating curve of 0.889 at 100x magnification (0.943 and 0.922 at 40x magnification). For invasive squamous cell carcinomas, high median average precision of 0.904 was achieved at 100x magnification. LimitationsSingle institution study with limited cases of SCC and rare NMSC. ConclusionDeep learning appears highly accurate for detecting skin cancers in Mohs frozen sections, supporting its potential for enhancing surgical margin control and increasing operational efficiency.

Penile Intra-epithelial Neoplasia (PeIN) positive margin in men treated with surgery for invasive Squamous Cell Carcinoma (SCC) or PeIN: Do we need to worry?

Penile Intra-epithelial Neoplasia (PeIN) positive margin in men treated with surgery for invasive Squamous Cell Carcinoma (SCC) or PeIN: Do we need to worry?

Defining the Longitudinal Risk of CIN 3+ for

To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and <CIN2 histology, stratified by biopsy result. The authors linked administrative databases including cytology, pathology, cancer registries, and physician billing history to identify participants referred to colposcopy between January 2012 and December 2013 with high-grade cytology (atypical squamous cells [ASC]-H, high-grade squamous intraepithelial lesion [HSIL], invasive squamous cell carcinoma, adenocarcinoma, atypical glandular cells [AGC], adenocarcinoma in situ) and had <CIN2 (with and without biopsy confirmation) at colposcopy. Three- and 5-year risks of CIN3 and invasive cervical cancer were generated using Kaplan-Meier survival analysis. Among 4,168 women referred to colposcopy for ASC-H, HSIL, squamous cell carcinoma, or adenocarcinoma, the 3- and 5-year CIN3 incidence rates were 17.7%/20.0% no biopsy, 13.0%/15.1% negative biopsy, and 18.9%/20.0% low-grade squamous intraepithelial lesion (LSIL) biopsies. The 3- and 5-year incidences of invasive cancer were: 1.25%/1.68% no biopsy, 0.78%/1.04% negative biopsy, and 0%/0% LSIL biopsy. When the initial cytology was AGC/adenocarcinoma in situ (n = 944), the 3- and 5-year rates of CIN3 were 7.42%/8.39% no biopsy, 7.41%/9.26% negative biopsy, and 7.69%/7.69% LSIL biopsy. The invasive cancer rates were 1.12%/1.54% no biopsy, 0.46%/0.46% negative biopsy, and 0.0%/0.0% LSIL biopsy. By screening cytology, participants referred for HSIL had the highest 3- and 5-year rates of CIN3 (18.9% and 21%) compared with AGC (7.22%/8.28%) and ASC-H (15.5%/18%). The 3- and 5-year invasive cancer rates were 1.38%/1.75% HSIL, 0.85%/1.17% AGC, and 0.91%/1.36% ASC-H. In participants referred for high-grade cytology where colposcopy shows <CIN2, the subsequent risk of invasive cancer at 5 years is sufficiently elevated to warrant close surveillance in colposcopy.

The Expression of PTTG1 as a Biomarker and Impact on Invasion and Growth of Oral Squamous Cell Carcinoma

The Expression of PTTG1 as a Biomarker and Impact on Invasion and Growth of Oral Squamous Cell Carcinoma

Role of Colposcopy in Diagnosing and Differentiating Types of Cervical Intraepithelial Neoplasia

Background: Preventing cervical cancer hinges on accurately detecting and treating high-grade cervical intraepithelial neoplasia (CIN2+) in individuals referred due to abnormal cervical cytology. While colposcopy has been a cornerstone in this process, concerns have arisen regarding its accuracy in CIN detection and differentiation. This study aims to assess the role of colposcopy in diagnosing and distinguishing various grades of CIN in clinically suspected patients. Methods: A descriptive cross-sectional study was conducted in the Department of Obstetrics &amp; Gynaecology at Rajshahi Medical College Hospital, Rajshahi, over 12 months from February 2019 to February 2020. The study involved 110 women aged 20-70 years who presented with clinical symptoms indicative of precancerous cervical lesions. Initial evaluations included visual inspection with 5% acetic acid (VIA) and Reid colposcopy. Biopsy samples were collected from the identified lesions using the colposcope, and these samples underwent histopathological examination. The study compared the diagnostic accuracy of colposcopy, including sensitivity, specificity, positive predictive value, and negative predictive value. Results: Colposcopic evaluations revealed that 80% of the participants exhibited positive lesions (CIN), while 20% displayed negative lesions (normal cervix or cervicitis). Among the colposcopically positive lesions, 50% were graded as CIN-1, 29.5% as CIN-2, and 20.5% as CIN-3. Subsequent histopathological examination of the colposcopy-directed biopsies confirmed CIN or dysplasia in 44.5% of cases. Within this group, 36.7% had CIN-1, 34.7% had CIN-2, 12.2% had CIN-3, 10.2% had invasive squamous cell carcinoma, and 6.2% had carcinoma in situ. Colposcopy demonstrated a sensitivity of 83.7% in diagnosing CIN, with a specificity of 23%, resulting in an overall diagnostic accuracy of 55%. However, when differentiating high-grade CIN from low-grade lesions, colposcopy exhibited a high sensitivity of 92.3% and moderate specificity of 67.7%, with an overall diagnostic accuracy of 75%. Conclusion: This study concludes that colposcopy is highly sensitive in diagnosing CIN but has limited specificity in excluding patients with normal cervix or cervicitis. Nevertheless, it exhibits optimal sensitivity in differentiating CIN2+ and carcinoma in situ from low-grade lesions and maintains moderate specificity in excluding low-grade CIN. Colposcopy remains a valuable tool in preventing and managing cervical cancer, particularly in identifying high-risk lesions.

TMEM16A enhances the activity of the Cdc42-NWASP signaling pathway to promote invasion and metastasis in oral squamous cell carcinoma

ObjectiveTo explore the relationship between TMEM16A and metastasis and development in oral squamous cell carcinoma (OSCC). Study DesignDatabases GEPIA and UALCAN were employed to analyze the relationship between the expression of TMEM16A and the survival of oral cancer patients. TMEM16A was knocked down and overexpressed in CAL27 and SCC-4 cells, respectively, and the malignant behavior, and the expression of key proteins were detected. The Cdc42-NWASP pathway was inhibited, and the effects of TMEM16A and Cdc42-NWASP pathway on promoting the malignant behavior of cancer cells were verified. The xenograft tumor model was constructed, and tumor growth, cell proliferation index, apoptosis and Cdc42-NWASP signal pathway activity were detected. ResultsThe expression of TMEM16A in oral cancer tissues was significantly higher than that in adjacent tissues, and the patients with high expression of TMEM16A had shorter survival time. Overexpression of TMTM16A can significantly promote the occurrence of cancer and reduce the apoptosis of cancer cells, while the activity of Cdc42 pathway was higher. Knocking down TMEM16A or inhibiting Cdc42-NWASP pathway can reverse the above results. ConclusionThe activation of Cdc42-NWASP pathway by TMEM16A high expression is closely related to OSCC, which may become a new therapeutic target to prevent OSCC metastasis.

Heparan-6-O-Endosulfatase 2 Promotes Invasiveness of Head and Neck Squamous Carcinoma Cell Lines in Co-Cultures with Cancer-Associated Fibroblasts.

Local invasiveness of head and neck squamous cell carcinoma (HNSCC) is a complex phenomenon supported by interaction of the cancer cells with the tumor microenvironment (TME). We and others have shown that cancer-associated fibroblasts (CAFs) are a component of the TME that can promote local invasion in HNSCC and other cancers. Here we report that the secretory enzyme heparan-6-O-endosulfatase 2 (Sulf-2) directly affects the CAF-supported invasion of the HNSCC cell lines SCC35 and Cal33 into Matrigel. The Sulf-2 knockout (KO) cells differ from their wild type counterparts in their spheroid growth and formation, and the Sulf-2-KO leads to decreased invasion in a spheroid co-culture model with the CAF. Next, we investigated whether a fucosylated chondroitin sulfate isolated from the sea cucumber Holothuria floridana (HfFucCS) affects the activity of the Sulf-2 enzyme. Our results show that HfFucCS not only efficiently inhibits the Sulf-2 enzymatic activity but, like the Sulf-2 knockout, inhibits Matrigel invasion of SCC35 and Cal33 cells co-cultured with primary HNSCC CAF. These findings suggest that the heparan-6-O-endosulfatases regulate local invasion and could be therapeutically targeted with the inhibitory activity of a marine glycosaminoglycan.

Research Landscape of Lymphovascular Invasion in Oral Squamous Cell Carcinoma: A Bibliometric Analysis From 1994 to 2023.

The primary factor affecting tumor biology is neo-lymphangiogenesis in solid epithelial malignancies like oral squamous cell carcinoma (OSCC). Determining the impact of lymphovascular invasion is critical in order to determine OSCC's locoregional and global dissemination. Bibliometric landscapes are vital to learning about the most recent advancements in the aforementioned topic because the ongoing research in OSCC is multifaceted. This analysis can reveal the progressions that might modernize OSCC diagnosis and treatment. The present analysis has been therefore undertaken to study the relevance and effects of lymphovascular invasion in OSCC utilizing co-occurrence of keywords analysis and co-authorship analysis in the PubMed database. The keywords included "lymphovascular invasion in oral squamous cell carcinoma" using the Boolean operator (AND). A cross-sectional bibliometric analysis of full-text articles from 1994 to 2023 using VOSviewer (Version 1.6.19; Centre for Science and Technology Studies, Leiden University, The Netherlands) was performed. The data obtained was analyzed for co-occurrence and co-authorship analysis using the VOSviewer standard protocol. The query revealed 296 searches in the PubMed database. Seven clusters were found with default colors in the representation of the entire term co-occurrence network, which also displayed a total link strength of 22,262. The items were categorized into clusters based on their commonalities. The labels' weights, as determined by links and occurrences, did not depend on one another, and the co-occurrence of keywords does not imply a causal association. In the item density visualization, item labels represented individual things. The number of items from a cluster that was close to the point was represented by the weight given to its color, which was formed by combining the colors of other clusters. A network of 57 authors who matched the search parameters was discovered by the co-authorship analysis. The network visualization map displayed three clusters with a total link strength of 184. The quantity of co-authorship relationships and the number of publications did not appear to be significantly correlated. In conclusion, this investigation uncovered a sizable body of bibliometric data that emphasizes key trends and advancements in the aforementioned theme. The observed variances may be a result of the various objectives of the researchers and journals, who collaborate to provide the best possible literature dissemination.

Inhibition of TGF-β signaling, invasion, and growth of cutaneous squamous cell carcinoma by PLX8394

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. The prognosis of patients with metastatic cSCC is poor emphasizing the need for new therapies. We have previously reported that the activation of Ras/MEK/ERK1/2 and transforming growth factor β (TGF-β)/Smad2 signaling in transformed keratinocytes and cSCC cells leads to increased accumulation of laminin-332 and accelerated invasion. Here, we show that the next-generation B-Raf inhibitor PLX8394 blocks TGF-β signaling in ras-transformed metastatic epidermal keratinocytes (RT3 cells) harboring wild-type B-Raf and hyperactive Ras. PLX8394 decreased phosphorylation of TGF-β receptor II and Smad2, as well as p38 activity, MMP-1 and MMP-13 synthesis, and laminin-332 accumulation. PLX8394 significantly inhibited the growth of human cSCC tumors and in vivo collagen degradation in xenograft model. In conclusion, our data indicate that PLX8394 inhibits several serine-threonine kinases in malignantly transformed human keratinocytes and cSCC cells and inhibits cSCC invasion and tumor growth in vitro and in vivo. We identify PLX8394 as a potential therapeutic compound for advanced human cSCC.

Periocular and ocular surface nonmelanoma skin cancer

Periocular and ocular surface nonmelanoma malignancies, including basal cell carcinoma (BCC), squamous cell carcinomas (SCC), and ocular surface squamous neoplasia (OSSN), are rare, but their management requires special considerations. The most common periocular malignancy is BCC, which constitutes 80% to 96% of tumors, followed by SCC, which represents 5% to 10% of tumors. OSSN represents a spectrum of diseases that encompass dysplastic alteration to the squamous epithelium of the eye. OSSN ranges from squamous dysplasia to conjunctival intraepithelial neoplasia/carcinoma in situ to invasive SCC, which is the most common ocular malignancy. These tumors can be staged using the eighth edition of the American Joint Committee on Cancer categorization system. The standard of care for periocular malignancies is Mohs micrographic surgery, while medical management with 5-fluorouracil (5-FU), interferon alfa-2b (INF), and mitomycin C (MMC) or “no touch” surgical excision are options for OSSN. Systemic therapies, including sonic hedgehog inhibitors for BCC and epidermal growth factor inhibitors and immune-checkpoint inhibitors for SCC, can be utilized for advanced disease. Recurrence rates are higher for periorbital and ocular malignancies than their respective cutaneous counterparts. These carcinomas and their respective treatments have unique side effects and considerations in an effort to preserve visual function.

Utilization of p53 and p16 Immunohistochemistry in the Classification of Human Papillomavirus–Associated, p53 Wild-Type, and p53 Abnormal Oral Epithelial Dysplasia

p53 immunohistochemistry (IHC) has recently been shown to be a clinically useful marker for predicting risk of progression to invasive squamous cell carcinoma in oral epithelial dysplasia (OED). The literature supports the use of p53 IHC as a marker to identify TP53 mutation in in situ and invasive vulvar lesions and as a surrogate marker for high-risk human papillomavirus (HPV) infection, but there is little documentation for similar use in OED. The purpose of this study was to determine whether p53 IHC is a reliable surrogate marker for detecting both TP53 mutation and high-risk HPV infection in OED. We studied 57 cases of OED (11 mild, 18 moderate, and 28 severe), and all were stained for p16 and p53 IHC. High-risk HPV RNA in situ hybridization (ISH) was performed in selected cases (all p16-positive cases and all OED showing abundant apoptotic cells and karyorrhectic cells; N = 27). Targeted next-generation sequencing (NGS) was performed in 33 p16-negative cases and all high-risk HPV RNA ISH–negative cases (N = 36). We identified 21 cases with p53 basal sparing patterns (mid-epithelial and markedly reduced [null-like]), 14 cases with p53 wild-type patterns (scattered basal and patchy basal/parabasal), and 22 cases with p53 abnormal patterns (18 overexpression, 3 null, and 1 novel cytoplasmic pattern). Among cases with p53 basal sparing patterns, 20 were positive for p16 (20/21, 95%), and all were positive for high-risk HPV RNA ISH (21/21, 100%). The 36 sequenced cases had IHC patterns concordant with TP53 mutation status in 92% (33/36) of lesions. This study demonstrates that p53 IHC expression patterns are sensitive and specific for detection of both high-risk HPV infection and TP53 mutation. Coupled with selective p16 IHC testing, this IHC panel can accurately subclassify OED into HPV-associated, p53 wild-type (conventional), and p53 abnormal OED.

Protocol for correlation of histological risk assessment/scoring system with a depth of invasion in oral squamous cell carcinoma

Introduction: The commonest type of cancer in the head and neck region is oral squamous cell carcinoma (OSCC) due to its high rates of occurrence and mortality. The early diagnosis of oral cancer gives better prognosis. Brandwein-Gensler criteria predict the early stage of OSCC cases with a high risk of locoregional recurrence. Objectives: To correlate Brandwein-Gensler criteria and depth of invasion of OSCC with three-year survival. Methodology: In the study, hematoxylin-eosin (HE)-stained section slides will be used to evaluate Brandwein and Gensler criteria and depth of invasion in resected tissue specimens of OSCC cases. Expected results: The present study will find the correlation between Brandwein-Gensler criteria and depth of invasion in OSCC in order to evaluate the locoregional recurrence in OSCC cases. In high-risk OSCC cases, there may be increased depth of invasion in resected tissues. Conclusions: We hypothesized that the correlation between Brandwein-Gensler criteria and depth of invasion can be used as an independent predictor for locoregional recurrence in OSCC.

Invasion of the bucco-mandibular space by oral squamous cell carcinoma: histopathological analysis of invasion pattern.

This study aimed to determine the patterns of invasion of oral squamous cell carcinoma (OSCC) into the bucco-mandibular space (BMS) using detailed histopathological analysis and to assess clinical outcomes. Patients with OSCC who underwent segmental mandibulectomy or hemi-mandibulectomy combined with resection of the BMS between 2012 and 2021 were included. The invasions of the BMS were classified into three patterns. Pattern A was defined as a horizontal invasion, Pattern B as a vertical invasion, and Pattern C as an expansive invasion. In total, 109 patients were reviewed. Of these 109 patients, the primary tumor affected the lower gingiva in 78 patients, the buccal mucosa in 18 patients, and was a primary intraosseous carcinoma of the mandible in 13 patients. Invasion of the BMS was significantly associated with a higher pathological T stage, positive/close margins, and lower disease-free survival (DFS) rates. The DFS rates were 86.7% and 66.0% in the BMS non-invasion and invasion groups, respectively. The DFS rates for each type of invasion were 82.1% for Pattern A, 67.4% for Pattern B, and 48.0% for Pattern C (P=0.277). Patients with BMS invasion have a poorer prognosis than those without invasion of the BMS. Therefore, adjuvant therapy is necessary, especially in Patterns B and C. Evaluation of preoperative BMS invasion patterns is important for predicting the prognosis of OSCC.