Publications by authors named "Ruta Gupta"

112 Publications

Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study.

Oral Oncol 2021 Feb 19;116:105210. Epub 2021 Feb 19.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Camperdown, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, University of Sydney, Sydney, NSW, Australia; Royal Prince Alfred Institute of Academic Medicine, Sydney Local Health District, NSW, Australia.

Background: In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables.

Methods: Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes.

Results: 3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years.

Conclusions: Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105210DOI Listing
February 2021

Young age is not a predictor of disease specific survival in oral cancer: A multi-institutional study.

Oral Oncol 2021 Feb 3;115:105162. Epub 2021 Feb 3.

Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia; Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, NSW, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, NSW, Australia. Electronic address:

Background: Over the last few decades evidence has accumulated for increasing incidence of oral cavity squamous cell carcinoma (OSCC) in a younger cohort. Prior studies examining the effect of age at diagnosis on prognosis have produced conflicting data.

Methods: A multi-institutional cohort study was performed across 6 different sites in Australia, Canada, India and Singapore. Disease-free (DFS), overall (OS) and disease-specific (DSS) survival were analysed. The association of the number of adverse features with survival outcomes was investigated.

Results: From 3179 patients, age was a significant predictor of OS with patients older than 45 years having a 66% increased risk of death (HR 1.66, 95%CI 1.33 - 2.07, p < 0.001). The number of adverse features was a significant predictor of OS with 3 or more adverse features having a 199% increased risk (HR 2.99, 95%CI 2.61-3.43. p < 0.001). The estimate effect was greater in patients ≤ 45 years (HR 3.49 vs HR 2.81). Age was not a significant predictor of DSS with similar rates of death from OSCC in multivariable models. The number of adverse features was a significant predictor of DFS with ≥ 3 adverse features having a 140% increased risk of death. The number of adverse features was a significant predictor of DSS with ≥ 3 adverse features having a 230% increased risk of disease specific death.

Conclusions: Age is not an independent predictor of disease specific mortality in OSCC. Differences in outcomes are due to the confounding effect of adverse clinicopathological features and the ability to tolerate surgery and adjuvant therapy.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105162DOI Listing
February 2021

Validation of the American Joint Committee on Cancer Staging in Squamous Cell Carcinoma of the Vermilion Lip.

Ann Surg Oncol 2021 Jan 2. Epub 2021 Jan 2.

Institute of Academic Surgery at RPA Hospital, Sydney, NSW, Australia.

Background: The vermilion lip is a unique anatomical junction between cutaneous and mucosal surfaces. Squamous cell carcinoma (SCC) of the vermilion lip (vlSCC) was previously classified as oral SCC (oSCC) under the American Joint Committee on Cancer (AJCC) 7th edition (AJCC7), but has been recategorized as a cutaneous SCC of the head and neck (HNcSCC) in the AJCC 8th edition (AJCC8). We investigated the locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for the various pathological T categories and disease stages of vlSCC as per AJCC8.

Methods: We performed a retrospective cohort study of 297 patients diagnosed with vlSCC between January 2004 and February 2019. For this study, vlSCC cases were staged according to both AJCC7 and AJCC8. Kaplan-Meier survival curves and Cox regression models were used to analyze differences in LRC, DFS, and OS between each pT category and disease stage, and log-rank tests were performed for subgroup analysis.

Results: Restaging of vlSCC using the AJCC8 resulted in 19% of patients being upstaged to pT3, and 16% being upstaged to stage III. No patients were downstaged in pT stage or overall stage.

Conclusions: Our study shows that when the AJCC8 HNcSCC staging system is applied to vlSCC, there are important aberrations leading to unwarranted upstaging of pT1 and redundancy of pT2. Understanding of these limitations are important in considering treatment escalation.
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http://dx.doi.org/10.1245/s10434-020-09431-4DOI Listing
January 2021

Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation.

Pathology 2021 Feb 30;53(2):141-156. Epub 2020 Dec 30.

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia; The University of Sydney, Sydney, NSW, Australia. Electronic address:

Immunotherapy with checkpoint inhibitors is well established as an effective treatment for non-small cell lung cancer and melanoma. The list of approved indications for treatment with PD-1/PD-L1 checkpoint inhibitors is growing rapidly as clinical trials continue to show their efficacy in patients with a wide range of solid tumours. Clinical trials have used a variety of PD-L1 immunohistochemical assays to evaluate PD-L1 expression on tumour cells, immune cells or both as a potential biomarker to predict response to immunotherapy. Requests to pathologists for PD-L1 testing to guide choice of therapy are rapidly becoming commonplace. Thus, pathologists need to be aware of the different PD-L1 assays, methods of evaluation in different tumour types and the impact of the results on therapeutic decisions. This review discusses the key practical issues relating to the implementation of PD-L1 testing for solid tumours in a pathology laboratory, including evidence for PD-L1 testing, different assay types, the potential interchangeability of PD-L1 antibody clones and staining platforms, scoring criteria for PD-L1, validation, quality assurance, and pitfalls in PD-L1 assessment. This review also explores PD-L1 IHC in solid tumours including non-small cell lung carcinoma, head and neck carcinoma, triple negative breast carcinoma, melanoma, renal cell carcinoma, urothelial carcinoma, gastric and gastroesophageal carcinoma, colorectal carcinoma, hepatocellular carcinoma, and endometrial carcinoma. The review aims to provide pathologists with a practical guide to the implementation and interpretation of PD-L1 testing by immunohistochemistry.
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http://dx.doi.org/10.1016/j.pathol.2020.10.007DOI Listing
February 2021

Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities.

Int J Mol Sci 2020 Dec 15;21(24). Epub 2020 Dec 15.

Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2-5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC metastases of the head and neck (designated UW-CSCC1 and UW-CSCC2). The cell lines genotypically and phenotypically resembled the original patient tumor and were tumorogenic in mice. Differences in cancer-related gene expression between the tumor and cell lines after various culturing conditions could be largely reversed by xenografting and reculturing. The novel drug susceptibilities of UW-CSCC1 and an irradiated subclone UW-CSCC1-R to drugs targeting cell cycle, PI3K/AKT/mTOR, and DNA damage pathways were observed using high-throughput anti-cancer and kinase-inhibitor compound libraries, which correlate with either copy number variations, targetable mutations and/or the upregulation of gene expression. A secondary screen of top hits in all three cell lines including -targeting drugs supports the utility of targeting the PI3K/AKT/mTOR pathway in this disease. UW-CSCC cell lines are thus useful preclinical models for determining targetable pathways and candidate therapeutics.
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http://dx.doi.org/10.3390/ijms21249536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765308PMC
December 2020

Thyroid gland metastasis from renal cell carcinoma: a case series and literature review.

ANZ J Surg 2020 Dec 14. Epub 2020 Dec 14.

Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.

Background: Renal cell carcinoma (RCC) is the most common malignancy that metastasises to the thyroid. This study aims to better understand the clinical characteristics of patients with thyroid metastasis from RCC.

Methods: A retrospective case series of patients with thyroid metastasis from RCC between 2008 and 2020 from two tertiary centres were examined. MEDLINE and PubMed database searches were performed to retrieve the relevant literature.

Results: Fifteen patients (eight males) were identified, with a median age of 57.0 (interquartile range (IQR) 51.0-63.0) at time of RCC diagnosis. Median time to thyroid metastasis was 92.0 months (IQR 40.0-156.0), with 12 (80.0%) patients undergoing thyroidectomy within 2 months of diagnosis. No patients developed post-operative complications or local thyroid recurrence. The two most common non-thyroid metastatic sites in this case series are lungs and bone (five patients, respectively; 33.3%) and pancreas (four patients; 26.7%). Ten (66.6%) patients underwent systemic chemotherapy, and five (33.4%) patients underwent radiotherapy for other sites of metastasis. Median survival following thyroid metastasis was 54.0 months (IQR 15.0-100.0). The literature review was conducted through MEDLINE and PubMed database searches, and 30 papers were considered relevant to this review. Results from our study are comparable to those reported in the literature.

Conclusion: Thyroid metastases can occur long after nephrectomy and portends a better prognosis. To prevent development of central neck disease, thyroidectomy should be considered.
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http://dx.doi.org/10.1111/ans.16482DOI Listing
December 2020

ALK alterations in salivary gland carcinomas.

Virchows Arch 2020 Nov 25. Epub 2020 Nov 25.

Department of Pathomorphology, Medical University of Gdańsk, ul. Smoluchowskiego, 17 80-211, Gdańsk, Poland.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.
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http://dx.doi.org/10.1007/s00428-020-02971-wDOI Listing
November 2020

Invitro and Invivo Study of PCL-Hydrogel Scaffold to Advance Bioprinting Translation in Microtia Reconstruction.

J Craniofac Surg 2020 Nov 10. Epub 2020 Nov 10.

ARC Centre of Excellence for Electromaterial Science, Intelligent Polymer Research Institute, University of Wollongong, Wollongong.

Background: Bioprinting has shown promise in the area of microtia reconstruction. However clinical translation has been challenged by the lack of robust techniques to control delivery of stem cells. Hybrid printing allowing multiple materials, both cell and support, to be printed together may overcome these challenges.

Objective: This study assesses the degradation behavior and tissue compatibility of hybrid scaffolds (PCL-Hydrogel) compared to single material Polycaprolactone (PCL) scaffolds in-vitro and in-vivo. Sheep demonstrate similar fascial anatomy to humans. This is the first reported study using a sheep model to study hybrid scaffolds for microtia.

Methods: PCL and PCL-Hydrogel samples of increasing porosity were subjected to an accelerated enzymatic degradation assay to study degradation behavior in-vitro. In addition, a 6-month study using Merino-Dorset sheep was conducted to compare the biological reaction of the host to PCL and PCL-hydrogel scaffolds.

Results: In-vitro degradation showed homogenous degradation of the scaffold. PCL presented the dominating influence on degradation volume compared to hydrogel. In-vivo, there was no evidence of skin irritation or infection over 6 months in both control and test, though PCL-hydrogel scaffolds showed higher levels of tissue ingrowth.

Conclusion: Homogenous degradation pattern of porous scaffolds may create less surrounding tissue irritation. Hybrid scaffolds had good biological compatibility and showed better tissue ingrowth than PCL alone.
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http://dx.doi.org/10.1097/SCS.0000000000007173DOI Listing
November 2020

Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi-institutional study.

Head Neck 2021 Feb 29;43(2):558-567. Epub 2020 Oct 29.

Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, Sydney, New South Wales, Australia.

Background: The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility.

Methods: Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions.

Results: AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease-specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS).

Conclusions: The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator.
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http://dx.doi.org/10.1002/hed.26512DOI Listing
February 2021

A prospective study of intraoperative assessment of mucosal squamous cell carcinoma margins in the head and neck.

Head Neck 2021 Feb 23;43(2):590-600. Epub 2020 Oct 23.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: In head and neck cancers, tumor margin assessment has important prognostic and therapeutic implications. Frozen section control of margins is commonly employed intraoperatively. However, this is not without limitations. The aim of this study is to determine whether intraoperative slicing of the whole specimen is feasible and what impact this may have on tumor margin assessment and the requirement for postoperative radiotherapy.

Methods: From September 2016 to August 2018, we recruited 22 patients as a pilot study looking at both the practicalities and the clinical relevance of whole margin tumor analysis intraoperatively. Our project is a prospective single arm study with historical controls.

Results: Forty-one percent of our patients required further intraoperative resection for close or involved margins. Seven of these patients who otherwise would have required adjuvant radiotherapy due to their margin status did not, after our intervention.

Conclusions: We found that although requiring resources, this process was feasible without unduly increasing operative times and with potential patient benefit including reduced incidence of adjuvant radiotherapy.
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http://dx.doi.org/10.1002/hed.26517DOI Listing
February 2021

Mismatch repair protein loss in cutaneous head and neck squamous cell carcinoma.

J Surg Oncol 2020 Dec 14;122(8):1755-1760. Epub 2020 Sep 14.

Central Clinical School, University of Sydney, Sydney, Australia.

Background: The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology-agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors.

Methods: The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively.

Results: The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes.

Conclusion: A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.
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http://dx.doi.org/10.1002/jso.26218DOI Listing
December 2020

Soft Tissue Metastases in Head and Neck Cutaneous Squamous Cell Carcinoma.

Laryngoscope 2020 Sep 14. Epub 2020 Sep 14.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

Objective: Soft tissue metastases (STM) in head and neck cutaneous squamous cell carcinoma (HNcSCC) are non-nodal based metastases to the parotid and cervical soft tissues of the head and neck. This is a unique subgroup of regional metastases amongst patients with cSCC and have been shown to be associated with poor prognosis. Detailed studies of this subgroup are lacking in the literature. A retrospective cohort analysis was performed to characterize the prognostic significance of STM in HNcSCC based on individual clinicopathological features.

Methods: Patients with HNcSCC with STM were identified from the Sydney Head and Neck Cancer Institute database. Clinicopathological characteristics were extracted from the histopathological reports. Recurrence and follow-up data were analyzed to determine disease-free and overall survival using the Kaplan-Meier method and Cox proportional hazards models.

Results: After excluding all patients with lymph node metastasis with no STM, there were 200 patients identified (161 parotid, 32 cervical, and seven with concurrent parotid and cervical STM) with a 5-year overall survival of 36%. In univariable analysis, age of patients, size of the deposits, location of the deposits, and patients that were not offered adjuvant radiotherapy have worse overall survival. However, on multivariable analysis, age and the number of STM deposits were independent factors that predict for worse survival.

Conclusion: The presence of STM in patients with HNcSCC is associated with poor prognosis. Increasing number of STM deposits, as well as involved margin of the regional excision, negatively impacted on the overall prognosis.

Level Of Evidence: Level III - retrospective cohort study. Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29064DOI Listing
September 2020

The American Joint Committee on Cancer staging for metastatic head and neck cutaneous squamous cell carcinoma: A multi-institutional study of within-stage heterogeneity and impact on prognostic performance.

Head Neck 2020 Nov 25;42(11):3235-3242. Epub 2020 Aug 25.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: The American Joint Committee on Cancer (AJCC) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) stratifies risk poorly. We hypothesized that this results from prognostic heterogeneity within N and TNM groups.

Methods: Retrospective analysis of disease-specific survival (DSS) in a multicenter study of 1146 patients with nodal metastases from HNcSCC.

Results: The majority of patients were classified as pN2a or pN3b (83.1%) and TNM stage IV (90.6%). On multivariate analysis, there was statistically significant prognostic heterogeneity within these groups based on the number and size of nodal metastases, immunosuppression, and perineural invasion. When stage IV patients were categorized into low, moderate, and high-risk groups based on adverse features, there was wide variation in prognosis with 5-year DSS ranging from 90% to 60% (P < .001).

Conclusions: The AJCC staging system stratifies risk poorly in HNcSCC due to significant prognostic heterogeneity within pN2a, pN3b, and stage IV groups.
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http://dx.doi.org/10.1002/hed.26369DOI Listing
November 2020

Number of nodal metastases and the American Joint Committee on cancer staging of head and neck cutaneous squamous cell carcinoma: A multicenter study.

Oral Oncol 2020 12 21;111:104855. Epub 2020 Aug 21.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, Australia.

Objectives: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification.

Materials And Methods: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ± adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE.

Results: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage.

Conclusion: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104855DOI Listing
December 2020

Thulium oxide nanoparticles as radioenhancers for the treatment of metastatic cutaneous squamous cell carcinoma.

Phys Med Biol 2020 11 5;65(21):215018. Epub 2020 Nov 5.

Illawarra Health and Medical Research Institute (IHMRI), Wollongong, NSW 2522, Australia. School of Chemistry and Molecular Bioscience, University of Wollongong, NSW 2522, Australia. Centre for Oncology Education and Research Translation (CONCERT), NSW 2170, Australia.

Metastases from cutaneous squamous cell carcinoma (cSCC) occur in 2%-5% of cases. Surgery is the standard treatment, often combined with adjuvant radiotherapy. Concurrent carboplatin treatment with post-operative radiotherapy may be prescribed, although it has not shown benefit in recent clinical trials in high-risk cSCC patients. The novel high-Z nanoparticle thulium (III) oxide has been shown to enhance radiation dose delivery to brain tumors by specific uptake of these nanoparticles into the cancerous tissue. As the dose-enhancement capacity of thulium oxide nanoparticles following radiotherapy against metastatic cSCC cells is unknown, its efficacy as a radiosensitizer was evaluated, with and without carboplatin. Novel and validated human patient-derived cell lines of metastatic cSCC were used. The sensitivity of the cells to radiation was investigated using short-term proliferation assays as well as clonogenic survival as the radiobiological endpoint. Briefly, cells were irradiated with 125 kVp orthovoltage x-rays (0-6 Gy) with and without thulium oxide nanoparticles (99.9% trace metals basis; 50 µg ml) or low dose carboplatin pre-sensitization. Cellular uptake of the nanoparticles was first confirmed by microscopy and found to have no impact on short-term cell survival for the cSCC cells, highlighting the biocompatibility of thulium oxide nanoparticles. Clonogenic cell survival assays confirmed radio-sensitization when exposed to thulium nanoparticles, with the cell sensitivity increasing by a factor of 1.24 (calculated at the 10% survival fraction) for the irradiated cSCC cells. The combination of carboplatin with thulium oxide nanoparticles with irradiation did not result in significant further reductions in survival compared to nanoparticles alone. This is the first study to provide in vitro data demonstrating the independent radiosensitization effect of high-Z nanoparticles against metastatic cSCC with or without carboplatin. Further preclinical investigations with radiotherapy plus high-Z nanoparticles for the management of metastatic cSCC are warranted.
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http://dx.doi.org/10.1088/1361-6560/abaa5dDOI Listing
November 2020

Pathology data set for reporting parathyroid carcinoma and atypical parathyroid neoplasm: recommendations from the International Collaboration on Cancer Reporting.

Hum Pathol 2020 Jul 17. Epub 2020 Jul 17.

University of Sydney, Sydney, New South Wales, 2006, Australia; Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, 2065, Australia.

Standardized pathologic reporting for cancers improves patient care and prognostic determination. However, access in many countries is limited. To address this issue, the International Collaboration on Cancer Reporting (ICCR), a not-for-profit organization, has the mission to develop and disseminate standardized data sets for global use. Within endocrine organs, the parathyroid gland has rarely been included in formal pathologic data sets. Utilizing an expert international panel of eleven members, an evidence-based data set was developed for parathyroid carcinoma and atypical parathyroid neoplasms. This data set consists of sixteen core (required) elements viewed as essential for documentation of these conditions. Characterizing parathyroid carcinomas and atypical neoplasms begins with correlative clinical information, the operative procedure, specimens submitted, and site of the disease. The pathologic features essential to document include parathyroid weight, size, classification, and, when a carcinoma, the tumor grade. Histologic grade of parathyroid carcinoma incorporates other core elements including necrosis, mitotic count, perineural invasion, and lymphovascular invasion. Documenting the extent of disease locally into adjacent organs, regionally, and distally is critical for staging. Pathologic staging is now included as part of the American Joint Committee on Cancer 8th edition and is included in this data set. Ancillary studies should be recorded when performed as noncore elements. Standardized pathologic data sets for endocrine organs including the parathyroid gland are now available through the ICCR website. These essential resources enhance international standardization for documenting these rare tumors for both patient care and future guidelines.
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http://dx.doi.org/10.1016/j.humpath.2020.07.008DOI Listing
July 2020

The incidence of squamous cell carcinoma of the oral tongue is rising in young non-smoking women: An international multi-institutional analysis.

Oral Oncol 2020 11 1;110:104875. Epub 2020 Jul 1.

Central Clinical School, University of Sydney, Parramatta Road, Camperdown, NSW 2050, Australia; Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW 2050, Australia. Electronic address:

Purpose: Increasing evidence is accumulating for an alarming rising incidence of oral tongue SCC in a younger cohort, particularly in developed countries. The aim of this study is to analyse the change in incidence of OSCC in patients under the age of 45 in developed nations in the Asia-Pacific region.

Patients And Methods: Population data was extracted from the Australian Cancer Incidence and Mortality 2017 database and National Registry of Diseases Office, Singapore to allow calculation of the incidence in the Australian and Singaporean populations. This was compared to multi-institutional data from four tertiary Australian institutions. The inclusion criteria were as follows: a) diagnosis of primary SCC of the mobile tongue; b) treatment with curative intent; c) complete histopathologic data; d) complete adjuvant treatment data; e) follow up data.

Results: Analysis of ACIM data demonstrated that there was a significant increase in the incidence of tongue SCC in those under the age of 45 in the Australian and Singaporean populations (p < 0.001). When analysed for gender, the incidence of tongue SCC increased at a significantly higher rate in females than males (p < 0.001). Similarly, in the multi-institutional analysis including 1814 patients, the number of females under the age of 45 with tongue SCC significantly increased over time (p < 0.001), with the proportion of smokers in this cohort decreasing over time.

Conclusion: The incidence of tongue SCC is rising in young females in developed nations in the Asia Pacific region, in keeping with observed epidemiological trends worldwide.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104875DOI Listing
November 2020

Trends in parotidectomy over 30 years in an Australian tertiary care center.

Head Neck 2020 Oct 3;42(10):2905-2911. Epub 2020 Jul 3.

Head and Neck Oncology, Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Background: Nomenclature, classification, and management of parotid tumors are constantly evolving; this study was performed to identify temporal trends in histology and facial nerve sacrifice in parotidectomy during a 30-year period (1987-2018).

Methods: Retrospective analysis of patients treated in a single tertiary-care institution during this time period was performed with analysis of temporal trends.

Results: Two thousand eight hundred and fifty-seven parotidectomies were performed; pleomorphic adenoma was the most common histology (34.3%), followed by skin cancer metastases (32.3%). Significant trends noted were increasing age (P < .001), fewer parotidectomies for inflammatory lesions (P < .001), reduced incidence of mucoepidermoid carcinoma (P = .048), increasing incidence of parotidectomy for cutaneous malignancies (P < .001), and reduced facial nerve sacrifice (P = .034).

Conclusion: In this contemporary series of parotid pathology, metastatic cutaneous malignancies accounted for a third of cases. Despite reducing facial nerve sacrifice in parotid disease, it is still required in approximately 15% of malignancy and needs to be discussed with all patients preoperatively.
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http://dx.doi.org/10.1002/hed.26335DOI Listing
October 2020

Molecular patterns in salivary duct carcinoma identify prognostic subgroups.

Mod Pathol 2020 10 26;33(10):1896-1909. Epub 2020 May 26.

Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia.

Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions. Androgen receptor (AR) was assessed by immunohistochemistry, and the Illumina TruSight 170 gene panel was used for DNA sequencing. Male gender, lympho-vascular invasion, lymph node metastasis, and smoking were significant predictors of disease-free survival. AR was present in 79%. Frequently encountered alterations were mutations in TP53 (51%), PIK3CA (32%) and HRAS (22%), as well as amplifications of CDK4/6 (22%), ERBB2 (21%), MYC (16%), and deletions of CDKN2A (13%). TP53 mutation and MYC amplifications were associated with decreased disease-free survival. Analysis of cancer pathways revealed that the PI3K pathway was most commonly affected. Alterations in the cell cycle pathway were associated with impaired disease-free survival (HR 2.6, P = 0.038). Three subgroups based on AR and ERBB2 status were identified, which featured distinct molecular patterns and outcome. Among AR positive SDCa, HRAS mutations were restricted to AR positive tumors without ERBB2 amplification and HRAS mutations featured high co-occurrence with PIK3CA alterations, which seems specific to SDCa. AR negative SDCa were associated with poor disease-free survival in multivariate analysis (HR 4.5, P = 0.010) and none of these tumors exhibited ERBB2 amplification or HRAS mutations. AR and ERBB2 status in SDCa thus classifies tumors with distinct molecular profiles relevant to future targeted therapy. Furthermore, clinical factors such as smoking and molecular features such as MYC amplification may serve as markers of poor prognosis of SDCa.
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http://dx.doi.org/10.1038/s41379-020-0576-2DOI Listing
October 2020

Regional Metastasis in Head and Neck Cutaneous Squamous Cell Carcinoma: An Update on the Significance of Extra-Nodal Extension and Soft Tissue Metastasis.

Ann Surg Oncol 2020 Aug 18;27(8):2840-2845. Epub 2020 Feb 18.

Sydney Head and Neck Cancer Institute, The Chris O'Brien Lifehouse, Camperdown, NSW, Australia.

Background: Soft tissue metastases (STMs) are reported to predict worse prognosis than extra-nodal extension (ENE) in metastatic head and neck cutaneous squamous cell carcinoma. This study aimed to update the authors' previous analysis of STM in a larger series.

Methods: The study analyzed 535 cases of consecutive cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007. A Cox proportional hazard model was used to determine the effect of STM, with adjustment for other relevant prognostic factors. Overall survival (OS) and disease-specific survival (DSS) were the primary end points.

Results: Of the 535 patients, 275 (51.4%) had STM. After adjustment for the effects of age, tumor location, number of metastatic deposits, and adjuvant radiotherapy, both STM (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.08-2.22; p = 0.018) and ENE (HR, 1.56; 95% CI 1.10-2.22; p = 0.013) were shown to be independent predictors of reduced OS, with similar size of effect.

Conclusion: In metastatic cSCC of the head and neck, STM is an independent predictor of reduced survival and has an impact on survival similar to that of ENE.
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http://dx.doi.org/10.1245/s10434-020-08252-9DOI Listing
August 2020

Development and validation of a multivariable prediction model for the identification of occult lymph node metastasis in oral squamous cell carcinoma.

Head Neck 2020 08 14;42(8):1811-1820. Epub 2020 Feb 14.

Department of Otolaryngology - Head and Neck Surgery, Geneva University Hospital and Faculty of Medecine of the University of Geneva, Geneva, Switzerland.

Background: There have been few recent advances in the identification of occult lymph node metastases (OLNM) in oral squamous cell carcinoma (OSCC). This study aimed to develop, compare, and validate several machine learning models to predict OLNM in clinically N0 (cN0) OSCC.

Methods: The biomarkers CD31 and PROX1 were combined with relevant histological parameters and evaluated on a training cohort (n = 56) using four different state-of-the-art machine learning models. Next, the optimized models were tested on an external validation cohort (n = 112) of early-stage (T1-2 N0) OSCC.

Results: The random forest (RF) model gave the best overall performance (area under the curve = 0.89 [95% CI = 0.8, 0.98]) and accuracy (0.88 [95% CI = 0.8, 0.93]) while maintaining a negative predictive value >95%.

Conclusions: We provide a new clinical decision algorithm incorporating risk stratification by an RF model that could significantly improve the management of patients with early-stage OSCC.
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http://dx.doi.org/10.1002/hed.26105DOI Listing
August 2020

Human papilloma virus related squamous cell carcinomas of the head and neck: diagnosis, clinical implications and detection of HPV.

Pathology 2020 Feb 27;52(2):179-191. Epub 2019 Dec 27.

Department of Anatomical Pathology, ACT Pathology, The Canberra Hospital, Woden, ACT, Australia; Australian National University Medical School, College of Health and Medicine, Canberra, ACT, Australia. Electronic address:

High-risk human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck is reported most commonly in the oropharynx but can also uncommonly be found in other sites such as the anterior oral cavity and sinonasal tract. While HPV positive oropharyngeal squamous cell carcinoma (HPV-OPSCC) has been shown to have a more favourable prognosis than conventional smoking- and alcohol-related anterior oral cavity squamous cell carcinoma (OSCC), HPV positive SCC arising elsewhere in the head and neck region does not carry the same favourable prognosis. HPV-OPSCC often tends to present with large cystic metastases in the cervical lymph nodes, with a clinically and radiologically occult primary. Correct diagnosis of the initial biopsy/cytology specimen is critical for directing further investigations and management. In recognition of its distinct biological behaviour, the 8th edition of the American Joint Commission on Cancer (AJCC 8) has proposed a separate clinical and pathological staging system for HPV-OPSCC compared to that for a conventional primary OSCC or neck metastasis of similar size. The new AJCC staging does not apply to other HPV positive SCC of the head and neck. This review examines the current biology of HPV positive SCC, focusing on HPV-OPSCC. The value and pitfalls of current detection methods of HPV are discussed with an emphasis on the role of the pathologist in the diagnosis and management of HPV positive SCC of the head and neck.
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http://dx.doi.org/10.1016/j.pathol.2019.10.008DOI Listing
February 2020

Development and validation of a targeted gene sequencing panel for application to disparate cancers.

Sci Rep 2019 11 19;9(1):17052. Epub 2019 Nov 19.

Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.
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http://dx.doi.org/10.1038/s41598-019-52000-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864073PMC
November 2019

Tumour mismatch repair protein loss is associated with advanced stage in oral cavity squamous cell carcinoma.

Pathology 2019 Dec 18;51(7):688-695. Epub 2019 Oct 18.

Central Clinical School, University of Sydney, Sydney, NSW, Australia; Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, NSW, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

An unexplained increase in the incidence of oral cavity squamous cell carcinoma (oSCC) has been observed despite decreasing smoking rates, particularly in younger patients. Links to defects in the DNA mismatch repair (MMR) system are well established in early onset colorectal, urothelial and gynaecological malignancies. MMR deficient patients treated with immune checkpoint inhibitors have demonstrated improved response rates. Studies exploring MMR status in head and neck squamous cell carcinoma (HNSCC) demonstrate conflicting results. This study explores the incidence of MMR protein loss and its association with clinicopathological features and outcome in oSCC. Immunohistochemical staining using tissue microarrays to assess the expression of MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed on 285 consecutive oSCC cases between 2000 and 2016. Data on smoking, alcohol and metachronous malignancies were retrospectively collected. Proportional hazards regression models were used to compare survival in MMR intact and deficient patients. MMR deficiency was seen in 21 patients (7.4%). MMR deficient tumours were associated with bone invasion (52% vs 32%, p=0.05), higher pT stage (pT4 in 57% vs 35%, p<0.001) and a higher number of metachronous malignancies (p=0.05). MMR deficiency was not associated with younger age at presentation or absence of smoking or alcohol. There was no significant association between MMR status and survival (overall survival hazard ratio 1.36; p=0.32). The incidence of MMR loss in oSCC is low and is not associated with young age at presentation. MMR deficiency in oSCC is associated with an increase in the number of metachronous malignancies and more advanced primary tumours.
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http://dx.doi.org/10.1016/j.pathol.2019.08.005DOI Listing
December 2019

Sentinel Node Biopsy in 105 High-Risk Cutaneous SCCs of the Head and Neck: Results of a Multicenter Prospective Study.

Ann Surg Oncol 2019 Dec 3;26(13):4481-4488. Epub 2019 Oct 3.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

Background: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC.

Methods: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years.

Results: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI.

Conclusion: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.
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http://dx.doi.org/10.1245/s10434-019-07865-zDOI Listing
December 2019

Association of PD-L1 expression in oral squamous cell carcinoma with smoking, sex, and p53 expression.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Dec 1;128(6):631-638. Epub 2019 Aug 1.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Central Clinical School, University of Sydney, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Objectives: The aim of this study was to investigate the association between oral cavity squamous cell carcinoma (OSCC) and PD-L1 expression, and smoking, and p53 expression.

Study Design: Histologic review of archival slides of patients with OSCC, obtained from the Sydney Head and Neck Cancer Institute database from 1995 to 2015, was undertaken with tissue microarray construction and immunohistochemistry to identify PD-L1 and p53 expression.

Results: Of the 255 patients identified, PD-L1 expression was observed in 70 (27.5%) and more commonly in females (odds ratio [OR] = 2.19; P = .005). PD-L1 expression of 1% or greater was associated with p53 expression (P = .019) and associated with absence of smoking (P = .06). PD-L1 expression, at 1%, was not significantly associated with overall survival (P = .482), disease-specific survival (P = .864), and disease-free survival (P = .731).

Conclusions: Our data demonstrate that PD-L1 expression of 1% or greater is more frequent in OSCC in females, nonsmokers, and in patients with p53-positive OSCC. These findings have important implications for immune therapy for OSCC.
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http://dx.doi.org/10.1016/j.oooo.2019.07.008DOI Listing
December 2019

Multifocal perineural invasion is a better prognosticator than depth of invasion in oral squamous cell carcinoma.

Head Neck 2019 11 5;41(11):3992-3999. Epub 2019 Sep 5.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Objectives: Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE).

Materials And Methods: Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1995 and 2018 were performed, with local failure (LF) and disease-specific mortality (DSS) as the primary endpoints.

Results: After adjusting for other adverse histopathological factors and adjuvant therapy, multifocal PNI was associated with a greater risk of LF (P = .01) and DSS (P = 0.02) compared to DOI. The effect of multifocal PNI was comparable to the effect of nodal metastases without ENE (P = 0.02). LF and DSS were not improved by the administration of adjuvant radiotherapy within unifocal or multifocal PNI groups.

Conclusion: Multifocal PNI is associated with a greater risk of death in OSCC than DOI. Its effect is comparable to that of nodal metastases (without ENE).
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http://dx.doi.org/10.1002/hed.25940DOI Listing
November 2019

Positive survival trend in metastatic head and neck cutaneous squamous cell carcinoma over four-decades: Multicenter study.

Head Neck 2019 11 12;41(11):3826-3832. Epub 2019 Aug 12.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: This study assessed changes over time of survival of head and neck cutaneous squamous cell carcinoma (HNcSCC) with lymph node metastases.

Methods: A multicenter analysis of 1301 patients with metastatic HNcSCC treated between 1980 and 2017. Differences in disease-specific survival (DSS) and overall survival (OS) by decade were assessed using multivariate Cox regression.

Results: Over the study period, we noted an increase in the proportion of patients aged over 80 years (3.9%-31.7%; P < .001) and immunosuppression (1.9%-9.9%; P = .03). After adjusting for number and size of metastatic nodes, extranodal extension, perineural invasion, immunosuppression, treatment, and institution, there was a reduction in risk of cancer-related mortality from 0.47 in 1990-1999 (P = .04) to 0.30 in 2000-2009 (P < .001) when compared to 1980-1989. This remained stable at 0.30 in 2010-2017 (P = .001). OS remained stable after 1990.

Conclusion: Despite an aging and more frequently immunosuppressed population, fewer patients are dying from metastatic HNcSCC.
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http://dx.doi.org/10.1002/hed.25912DOI Listing
November 2019

Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted therapies?

J Clin Pathol 2020 Jan 12;73(1):17-22. Epub 2019 Jul 12.

Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

Objective: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management.

Methods: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed.

Results: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance ( S821F, T670I, mutations at codons 12 and 13).

Conclusion: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
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http://dx.doi.org/10.1136/jclinpath-2019-206038DOI Listing
January 2020

Mammary-type myofibroblastoma in the head and neck region.

Pathology 2019 Aug 17;51(5):544-547. Epub 2019 Jun 17.

Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, The University of Sydney, NSW, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.pathol.2019.01.015DOI Listing
August 2019