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• This is an analysis of stage III-IV oral cancer patients, comparing TNM 8 to TNM 7. • TNM 8 is a better prognosticator for OS, DFS and early disease recurrence. • On MVA, TNM 8 stage, margin status and performance status affect overall survival. • Patients aged < 60 years who smoked less were more likely to recur within 12 months. To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients. [ABSTRACT FROM AUTHOR]

• High content image analysis allows single-cell evaluation of HPV + OpSCC H&E slides. • Established and novel prognostic features have been identified. • Neural network model can predict patient outcomes with promising accuracy. • Automated H&E analysis is prognostic without additional diagnostic tests. Routine haematoxylin and eosin (H&E) photomicrographs from human papillomavirus-associated oropharyngeal squamous cell carcinomas (HPV + OpSCC) contain a wealth of prognostic information. In this study, we developed a high content image analysis (HCIA) workflow to quantify features of H&E images from HPV + OpSCC patients to identify prognostic features and predict patient outcomes. First, we have developed an open-source HCIA tool for single-cell segmentation and classification of H&E images. Subsequently, we have used our HCIA tool to analyse a set of 889 images from diagnostic H&E slides in a retrospective cohort of HPV + OpSCC patients with favourable (FO, n = 60) or unfavourable (UO, n = 30) outcomes. We have identified and measured 31 prognostic features which were quantified in each sample and used to train a neural network (NN) model to predict patient outcomes. Univariate and multivariate statistical analyses revealed significant differences between FO and UO patients in 31 and 17 variables, respectively (P < 0.05). At the single-image level, the NN model had an overall accuracy of 72.5% and 71.2% in recognising FO and UO patients when applied to test or validation sets, respectively. When considering 10 images per patient, the accuracy of the NN model increased to 86.7% in the test set. Our open-source H&E analysis workflow and predictive models confirm previously reported prognostic features and identifies novel factors which predict HPV + OpSCC outcomes with promising accuracy. Our work supports the use of machine learning in digital pathology to exploit clinically relevant features in routine diagnostic pathology without additional biomarkers. [ABSTRACT FROM AUTHOR]

Cancers, such as squamous cell carcinoma, frequently invade as multicellular units. However, these invading units can be organised in a variety of ways, ranging from thin discontinuous strands to thick 'pushing' collectives. Here we employ an integrated experimental and computational approach to identify the factors that determine the mode of collective cancer cell invasion. We find that matrix proteolysis is linked to the formation of wide strands but has little effect on the maximum extent of invasion. Cell-cell junctions also favour wide strands, but our analysis also reveals a requirement for cell-cell junctions for efficient invasion in response to uniform directional cues. Unexpectedly, the ability to generate wide invasive strands is coupled to the ability to grow effectively when surrounded by extracellular matrix in three-dimensional assays. Combinatorial perturbation of both matrix proteolysis and cell-cell adhesion demonstrates that the most aggressive cancer behaviour, both in terms of invasion and growth, is achieved at high levels of cell-cell adhesion and high levels of proteolysis. Contrary to expectation, cells with canonical mesenchymal traits - no cell-cell junctions and high proteolysis - exhibit reduced growth and lymph node metastasis. Thus, we conclude that the ability of squamous cell carcinoma cells to invade effectively is also linked to their ability to generate space for proliferation in confined contexts. These data provide an explanation for the apparent advantage of retaining cell-cell junctions in squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

Objectives: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity‐modulated (chemo)radiotherapy [(C)RT]. Materials and methods: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end‐point was post‐failure survival (PFS). Results: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)‐negative; n = 16 HPV‐positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two‐year PFS for the entire population was 30.6%; 20.5% for HPV‐negative and 43.8% for HPV‐positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). Conclusion: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV‐positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy is an increasingly recognised option for accurate staging and subsequent management of the clinically negative neck in early stage oral cavity squamous cell carcinoma. However, the technique is currently underused due to several logistic constraints including increased burden on pathology services. Here, we describe the feasibility of an outsourced centralised pathology processing and reporting service for sentinel lymph node biopsies in oral cavity squamous cell carcinoma. Patients and methods: The Southeast England Consortium comprises four surgical centres utilising a central pathology service. Consecutive cases between January 2016 and February 2020 were retrospectively evaluated for survival outcomes and laboratory turnaround times. Results: Twenty‐eight per cent from a cohort of 139 patients had positive sentinel nodes. There was a trend towards greater overall, disease‐free and disease‐specific survival (OS, DFS and DSS, respectively) in sentinel node negative compared to sentinel node positive patients, but these differences were not statistically significant. The sensitivity, negative predictive value and false negative rate were 92.8%, 97.0% and 6.8%, respectively. The mean and mode laboratory TAT were 5 and 4 working days, respectively. Conclusion: An outsourced centralised pathology service is a feasible option to widen the availability of sentinel node biopsy in oral cavity squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral potentially malignant disorders (OPMDs) include a group of oral mucosal diseases with different morphological characteristics that are able to progress to oral squamous cell carcinoma (OSCC). Given OSCC's poor prognosis and high mortality, early diagnosis is a priority step in OSCC. Extrinsic and intrinsic risk factors and etiologies are involved in developing and malignant transformation of oral lesions, and different molecular alterations have been described in early lesions associated with a potential malignant behavior. This review summarizes the information about clinical, morphological and molecular features of OPMDs, with an emphasis on the early detection techniques and an overview of the surgical and systemic therapies' effectiveness. Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs' development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combination), has suffered a dramatic change in last years, especially with the introduction of immunotherapy. However, most cases are diagnosed during the advanced stage of the disease, decreasing drastically the survival rate of the patients. Hence, early diagnosis of premalignant conditions (OPMDs) is a priority in oral cancer, as well as a massive education about risk factors, the understanding of mechanisms involved in malignant progression and the development of specific and more efficient therapies. The aim of this article is to review epidemiological, clinical, morphological and molecular features of OPMDs, with the purpose to lay the foundation for an exhaustive comprehension of these lesions and their ability of malignant transformation and for the development of more effective and personalized treatments. [ABSTRACT FROM AUTHOR]