Oral Oncology 2022-05-28

Natural “epidrugs” and the need of basket trials in the treatment of oral cancer in India

A.S. Smiline Girija

Publication date 28-05-2022


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Rapid physical and emotional palliation from QUAD shot radiotherapy to a frail elderly patient with stage IV parotid gland cancer-associated facial paralysis and pain when no other palliative intervention was available during COVID-19 pandemic

Whoon Jong Kil

Publication date 27-05-2022


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Cecal mass: An unusual site of metastasis from HPV-associated oropharyngeal cancer

Soon Khai Low, Clay T. Reed, Corina Millo, Evrim B. Turkbey, Jonathan Hernandez, Charalampos S. Floudas

Publication date 24-05-2022


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Plasma circulating tumor DNA as a molecular marker for oral cancer

Arumugam Paramasivam

Publication date 22-05-2022


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Development and tumorigenic potential of TP53: A therapeutic target for head and neck squamous cell carcinoma

Jayaraman Selvaraj, Dinesh Yasothkumar, Veeraraghavan Vishnu Priya, A. Thirumal Raj, Somasundaram Dinesh Babu, Shankargouda Patil

Publication date 22-05-2022


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The implications of gene mutations in salivary DNA for noninvasive diagnosis of head and neck cancer with a focus on oral cancer

Xi Yang, Hao Song, Tong Ji, Guanhuan Du, Wei Liu

Publication date 21-05-2022


DNA-based liquid biopsy as a diagnostic strategy of head and neck squamous cell carcinoma (HNSCC) has emergingly gained momentum. In this letter, we identified 6 studies contained 274 patients with HNSCC focused on gene mutations in salivary DNA. We observe that the incidence of DNA mutations with at least one gene mutated ranges from 63% to 95.9%, and the most frequently examined gene mutations are TP53, CDKN2A, PIK3CA, FAT1, and NOTCH1. Meanwhile, studies have demonstrated that saliva had a greater sensitivity and much higher quantitative values than plasma in both tumor DNA count and variant allele frequency. Interestingly, more tumor-derived mutations were detected in salivary DNA among patients with tumors arising in oral cavity compared to in oropharynx, larynx, and hypopharynx. Collectively, it is feasibility to identify somatic mutations in driver genes using saliva samples to noninvasively diagnose HNSCC, especially in oral cavity cancer and even at early stages of the disease. Larger well-designed studies are needed to consolidate the evidence.

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Oral submucous fibrosis induced by graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Binjie Liu, Jingwen Cai, Wenjie Li, Gui Liu, Jun Chen

Publication date 21-05-2022


Graft-versus-host disease (GVHD) is one of the most common and serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). About 45%∼83% of patients develop GVHD in the oral cavity. There has no medical records of oral submucous fibrosis (OSF) induced by GVHD after allo-HSCT, which should be brought to the attention of dentists.

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Anti-PD-1 plus anti-HER2 and chemotherapy showed superior and durable clinical benefit in a patient with advanced salivary duct carcinoma

Pei Ma, Hao-Yang Shen, Dong-Sheng Chen, Zhong-Yu Lu, Wen Gao, Yong-Qian Shu

Publication date 21-05-2022


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Cerenkov luminescence imaging: A future nuclear imaging modality of head and neck oncology patients in low-income countries?

Ullas Mony, Vishnu Priya Veeraraghavan

Publication date 20-05-2022


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Types of endoscopic surgical approaches for benign parapharyngeal space tumors

Ru Tang, Song Mao, Shixian Liu, Zhipeng Li, Huaming Zhu, Weitian Zhang

Publication date 17-05-2022


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Early detection of oral malignancies may involve the development of tele-expertise in dentistry

Emmanuelle Vigarios, Saman Warnakulasuriya, Antoine Piau, Nicolas Giraudeau, Delphine Maret

Publication date 14-05-2022


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Targeting cancer associated fibroblasts – A TGF-β based immunotherapy for head and neck squamous cell carcinoma

Jayanthi Pazhani, Selvaraj Jayaraman, Vishnu Priya Veeraraghavan, Dinesh Babu Somasundaram, A. Thirumal Raj, Shankargouda Patil

Publication date 14-05-2022


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Comment on: The prognostic value of radiologic extranodal extension in nasopharyngeal carcinoma: Systematic review and meta-analysis

Yan Jiang, Shaohua Yang, Yinhui Qi

Publication date 14-05-2022


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Intraosseous rhabdomyosarcoma of the maxilla with TFCP2 fusion: A rare aggressive subtype with predilection for the gnathic bones

John Lennon Silva Cunha, Israel Leal Cavalcante, Caio César da Silva Barros, Pollianna Muniz Alves, Cassiano Francisco Weege Nonaka, Assis Filipe Medeiros Albuquerque, Oslei Paes de Almeida, Bruno Augusto Benevenuto de Andrade, Roberta Barroso Cavalcante

Publication date 14-05-2022


Rhabdomyosarcomas (RMS) are malignant tumors with skeletal muscle differentiation extremely rare in intraosseous sites. We reported a rare case of an aggressive intraosseous RMS found in the maxilla of a 17-year-old female patient with five months of evolution. Computed tomography revealed a large osteolytic lesion extending from tooth 21 to 27, causing buccal and lingual cortical plate perforation. Microscopically, the lesion showed a proliferation of spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm, arranged in an interlaced fascicle pattern. The nuclei ranged from vesicular with distinct nucleoli to hyperchromatic. A focal component of plump to epithelioid cells with a moderate amount of eosinophilic cytoplasm was seen at the periphery of the tumor. The immunohistochemical analysis revealed positivity for desmin, MyoD1, and myogenin (scattered cells). S-100, SOX10, HMB45, β-catenin, and CD34 were negative. Ki-67 was positive in 30% of tumor cells. Fluorescence in situ hybridization (FISH) analysis showed the presence of a FUS-TFCP2 fusion. The diagnosis was intraosseous RMS with TFCP2 fusion. Surgical excision followed by chemo- and radiotherapy was carried out; however, the patient died of disease nine months after the treatment. Because of the rarity and non-specific signs and symptoms, the clinical diagnosis of intraosseous RMS is difficult and often overlooked. Therefore, careful histopathological evaluation, supported by immunohistochemical and molecular analysis, is essential to correct diagnosis. Early surgical excision with tumor-free margins and prolonged follow-up are strongly recommended.

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Engineered therapeutic bacteria for the treatment of oral squamous cell carcinoma

Vijayashree Priyadharsini Jayaseelan, Smiline Girija A.S, Paramasivam Arumugam

Publication date 10-05-2022


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Comment on circulatory miRNAs as therapeutic molecules for oral potentially malignant disorder and oral squamous cell carcinoma

Xi Yang, Tian Zhou, Tong Ji, Hao Jia, Wei Liu

Publication date 10-05-2022


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The role of concomitant chemoradiotherapy versus radiation alone in T1-3N0 HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

Jay C. Shiao, Douglas Holt, Colton Ladbury, Dexiang Gao, Bernard Jones, Sana D. Karam, Arya Amini

Publication date 24-05-2022


To evaluate the role of curative intent concurrent chemoradiation (CCRT) vs radiation (RT) alone for T1-T3N0 HPV-positive and HPV-negative oropharyngeal squamous cell cancer (OPSCC). The NCDB was queried for patients diagnosed between 2010 and 2017 with cT1-3N0M0 OPSCC treated with definitive RT or CCRT. Univariable analysis (UVA) and multivariable analysis (MVA) Cox regression analysis was performed with OS as the endpoint. Propensity score matching (PSM) 1:1 was performed. Interaction test to assess heterogeneity of treatment effect. A total of 2830 patients were queried. On MVA, CCRT was associated with improved OS for T3N0 tumors (HR 0.49; 95% CI 0.39-0.63) but not for T1N0 (HR 1.43; 95% CI 0.99-2.07) and T2N0 (HR 0.92; 95% CI 0.75-1.13). For T3 patients, CCRT improved OS for HPV-negative (HR 0.43; 95% CI 0.31-0.59) and HPV-positive tumors (HR 0.39; 95% CI 0.25-0.61). After PSM, CCRT was not statistically different to RT for patients with T1-2N0 HPV-negative tumors (HR 1.10; 95% CI 0.85-1.43; p = 0.48) and T1-2N0 HPV-positive tumors (HR 1.15; 95% CI 0.79-1.68; p = 0.45). After PSM, CCRT improved OS compared to RT alone for patients with T3N0 HPV-negative (HR 0.43; 95% CI 0.31-0.59; p < 0.01) and HPV-positive tumors (HR 0.39; 95 %CI 0.25-0.61; p < 0.01). CCRT is associated with improved OS in HPV-positive and HPV-negative T3N0 OPSCC. RT alone vs. CCRT demonstrated similar OS for T1-T2N0 OPSCC for both HPV negative and HPV positive tumors.

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Enhanced recovery after surgery (ERAS) in head and neck oncologic surgery: Impact on return to intended oncologic therapy (RIOT) and survival

Kimberley L. Kiong, Amy Moreno, Catherine N. Vu, Gang Zheng, David I. Rosenthal, Randal S. Weber, Carol M. Lewis

Publication date 21-05-2022


Enhanced Recovery After Surgery (ERAS) pathways in head and neck cancer (HNC) have shown to improve perioperative outcomes and reduce complications. The longer term implications on adjuvant treatment and survival have not been studied. We hereby report the first study on the impact of an ERAS pathway on return to intended oncologic treatment (RIOT) and overall survival (OS) in HNC. 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between March 1, 2016 and March 31, 2019 were matched to controls over the same interval. Demographic, tumor and adjuvant therapy-related data were collected, including time to adjuvant therapy(TAT) and treatment package time(TPT). Risk factors for TAT > 42 days and TPT ≥ 85 days were assessed. OS was compared and risk factors for inferior OS determined. Baseline characteristics including co-morbidities and tumor stage were similar. Of 179 patients planned for adjuvant treatment, there was no difference in RIOT rate (89.0% vs 87.5%, p = 0.753), proportion of TAT > 42 days of surgery (55.6% vs 59.7%, p = 0.642), or TPT ≥ 85 days (48.1% vs 57.1, p = 0.258), for the ERAS and control groups, respectively. On multivariate analysis, alcohol use (OR 3.58; 95 %CI 1.11-11.52) and recurrent disease status (OR 2.88; 95 %CI 1.40-5.93) were independently associated with prolonged TAT. Three-year OS was similar between the ERAS and control groups (73% vs 76%, p = 0.521). ERAS has not shown to improve RIOT or OS in the current study. However, its benefit for perioperative outcomes is undeniable and further studies are required on longer term quality and survival outcomes.

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Pattern of cervical lymph node metastases in squamous cell carcinoma of the upper oral cavity – How to manage the neck

Christian Doll, Friedrich Mrosk, Jonas Wuester, Anna-Sophie Runge, Felix Neumann, Kerstin Rubarth, Max Heiland, Kilian Kreutzer, Jan Voss, Jan-Dirk Raguse, Steffen Koerdt

Publication date 17-05-2022


Oral squamous cell carcinoma (OSCC) arising from the upper oral cavity is rare compared to other localizations. While cervical lymph node metastasis (CLNM) can be predicted to some extent, the probability of occult CLNM remains high. The aim of this study is to determine risk factors affecting clinical decision making. A retrospective analysis of patients surgically treated between 2012 and 2017 for OSCC of the upper oral cavity was performed. A total of 66 patients were included. Of these, 25 patients (37.9%) presented with CLNM after histopathological examination (pN+/cN0: 10/44 (22.7%); pN+/cN+: 15/22 (68.2%)). Lymph vessel infiltration (p = 0.03) and grade of differentiation (p = 0.03) were associated with an increased probability for CLNM. Patients with positive nodal disease at the time of primary surgery showed higher tumor depth of invasion (DOI) than patients without CLNM (mean 10.3 mm ± 6.9 versus mean 6.1 mm ± 4.9; p = 0.02). The optimal DOI cutoff value for the prediction of CLNM was 4.5 mm. The OS was significantly higher in patients with a tumor DOI ≤ 4.5 mm (p = 0.01). Elective neck dissection should be preferably performed for OSCC of the upper oral cavity. For early-stage and clinically node-negative patients, sentinel-lymph node biopsy can be an alternative, especially in patients with a DOI ≤ 4.5 mm. Since this group had no occult CLNM below this DOI cutoff value, watch and wait might be an alternative for selected patients.

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Placement technique impacts gastrostomy tube-related complications amongst head and neck cancer patients

David Forner, Florence Mok, Neil Verma, Irene Karam, David Goldstein, Kevin Higgins, Danny Enepekides, Ashlie Nadler, Robyn Pugash, Zain Husain, Kelvin Chan, Martin Smoragiewicz, Lawrence Cohen, Jeffrey W. Hazey, Eleanor C. Fung, Stephen Y. Kang, Nolan B. Seim, Colleen Simpson, Antoine Eskander

Publication date 16-05-2022


Percutaneous endoscopic gastrostomy (PEG) placement is essential for the provision of enteral nutrition in select head and neck cancer (HNC) patients. Minimally invasive tube placement is facilitated through one of two techniques, push or pull, but there have been conflicting results regarding safety profiles of these procedures. The objectives of this study were to determine the association of PEG insertion technique with gastrostomy tube complications, including stomal metastases. A multi-institutional retrospective cohort study of patients with HNC undergoing PEG insertion by either the pull (gastroscope assisted) or push (fluoroscopy assisted) technique was performed. Tube-related complications included infection, dislodgement, deterioration, leak, and other. Adjusted analysis was performed via a multivariable logistic regression model. 1,575 patients were included across three institutions. Tube-related complications occurred in 36% of patients, the most common being peristomal leak (13%) and infection (16%). The push technique (OR 2.66, 95% CI: 1.42-4.97), and the presence of T4 disease (OR 4.62, 95% CI: 1.58-13.51), were associated with a greater risk of developing any tube-related complication. Infection rates were similar between pull and push cohorts. All detected stoma metastases occurred with the pull technique, with an overall prevalence of 0.32% amongst the cohort. The push technique is associated with a greater risk of developing any tube-related complication, but the rate of stomal metastases may be higher with the pull technique. There is potential for quality improvement measures to improve tube-related complications associated with either technique.

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Salvage total glossectomy and total glosso-laryngectomy: Are they worth it? A GETTEC French multicenter study

Paul Mazerolle, Carine Fuchsmann, Philippe Schultz, Nadia Benmoussa, Olivier Malard, Alexandre Bozec, Sophie Deneuve, Mireille Folia, Marion Perréard, Audrey Lasne-Cardon, Emilien Chabrillac, Sébastien Vergez, Léonor Chaltiel, Agnès Dupret-Bories

Publication date 15-05-2022


Salvage total glossectomy (TG) or total glosso-laryngectomy (TGL) remain controversial, as highly morbid procedures. The objective was to describe oncological and functional outcomes after salvage TG or TGL. We performed a multicenter retrospective study, including patients with previous neck irradiation undergoing TG or TGL for squamous cell carcinoma involving the base of tongue.
We included 42 patients: 27 in the TG group and 15 in the TGL group. For the entire cohort, median OS and DFS were estimated at 19 months (95% IC [14-44]) and 10 months (95% IC [7-13]) respectively, with no difference between the two groups. After a median follow-up of 90 months, 10 patients (24%) were alive and free of disease. Att he end of follow-up, we noted a gastrostomy dependency of 89% and 87 %respectively in the TG and TGL group, and 48% of patients in the TG group had a tracheotomy. Although local control is difficult to achieve after salvage TG or TGL, these procedures are associated with acceptable survival and chance of cure for a last-resort situation. TG and TGL can be proposed in selected motivated patients after careful shared decision-making.

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Outcomes with culture-directed antibiotics following microvascular free tissue reconstruction for osteonecrosis of the jaw

Riddhima Agarwal, Taylor E. Freeman, Michael M. Li, Akash N. Naik, Ramez W. Philips, Stephen Y. Kang, Enver Ozer, Amit Agrawal, Ricardo L. Carrau, James W. Rocco, Matthew O. Old, Nolan B. Seim

Publication date 10-05-2022


Radiation (ORNJ) and bisphosphonate-related (BRONJ) osteonecrosis of the jaw represent challenging entities to treat, with many patients requiring segmental resection and reconstruction with microvascular free tissue transfer (MFTT) in the setting of failed conservative therapy. Microvascular reconstruction is associated with higher post-operative complication rates when performed for advanced osteonecrosis versus oncologic defects. We hypothesize that basing antibiotic therapy on cultures obtained from the healthy bone marrow following resection during MFTT for ORNJ or BRONJ reduces rates of post-operative wound and surgical complications. In a retrospective cohort study spanning January 2016 to October 2018, 44 patients undergoing MFTT for ORNJ or BRONJ were identified.
Patients were categorized into two cohorts: residual healthy marrow culture (n = 11; RHM), treated with antibiotics guided by cultures from healthy appearing mandible, and all others (n = 33; AO), treated with antibiotics guided by cultures from resected necrotic bone or purulent drainage. Patient, reconstruction, and outcome variables were compared via appropriate statistical tools. 81.8% of the RHM cohort versus 24.2% of the AO cohort received long-term IV antibiotics. Rates of post-operative wound complications, including those necessitating operative management, were significantly lower in the RHM cohort. Rates of flap failure were similar across both groups. Administration of long-term IV antibiotics directed by native mandible cultures may decrease complication rates following MFTT for ORNJ or BRONJ by treating residual, smoldering infection. Concurrently, transplantation of well-vascularized free tissue likely improves antibiotic delivery. Findings are crucial for the development of a standardized treatment algorithm following microvascular reconstruction for advanced osteonecrosis.

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Non-invasive imaging of oral potentially malignant and malignant lesions: A systematic review and meta-analysis

Pramila Mendonca, Sumsum P Sunny, Uma Mohan, Praveen Birur N, Amritha Suresh, Moni A Kuriakose

Publication date 27-05-2022


Non-invasive (NI) imaging techniques have been developed to overcome the limitations of invasive biopsy procedures, which is the gold standard in diagnosis of oral dysplasia and Oral Squamous Cell Carcinoma (OSCC). This systematic review and meta- analysis was carried out with an aim to investigate the efficacy of the NI-imaging techniques in the detection of dysplastic oral potentially malignant disorders (OPMDs) and OSCC. Records concerned in the detection of OPMDs, Oral Cancer were identified through search in Pub Med, Science direct, Cochrane Library electronic database (January 2000 to October 2020) and additional manual searches. Out of 529 articles evaluated for eligibility, 56 satisfied the pre-determined inclusion criteria, including 13 varying NI-imaging techniques. Meta-analysis consisted 44 articles, wherein majority of the studies reported Autofluorescence (AFI-38.6%) followed by Chemiluminescence (CHEM), Narrow Band Imaging (NBI) (CHEM, NBI-15.9%), Fluorescence Spectroscopy (FS), Diffuse Reflectance Spectroscopy (DRS), (FS, DRS-13.6%) and 5aminolevulinic acid induced protoporphyrin IX fluorescence (5ALA induced PPIX- 6.8%). Higher sensitivities (Sen) and specificities (Spe) were obtained using FS (Sen:74%, Spe:96%, SAUC=0.98), DRS (Sen:79%, Spe:86%, SAUC = 0.91) and 5 ALA induced PPIX (Sen:91%, Spe:78%, SAUC = 0.98) in the detection of dysplastic OPMDs from non-dysplastic lesions(NDLs). AFI, FS, DRS, NBI showed higher sensitivities and SAUC (>90%) in differentiating OSCC from NDLs. Analysed NI-imaging techniques suggests the higher accuracy levels in the diagnosis of OSCC when compared to dysplastic OPMDs. 5 ALA induced PPIX, DRS and FS showed evidence of superior accuracy levels in differentiation of dysplastic OPMDs from NDLs, however results need to be validated in a larger number of studies.

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Corrigendum to “The impact of frailty on mortality in non-surgical head and neck cancer treatment: Shifting the clinical paradigm” Oral Oncol. 126 (2022) 105766

Leila J. Mady, Khalil Baddour, Jacob C. Hodges, Linda C. Magaña, Hannah L. Schwarzbach, Jeffrey D. Borrebach, Marci L. Nilsen, Jonas T. Johnson, Daniel E. Hall

Publication date 07-05-2022


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Quantitative malignant index diagnosis system (qMIDS) for effective diagnosis of oral premalignant lesions

J. Vijayashree Priyadharsini, P. Anitha

Publication date 09-05-2022


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Myxoid liposarcoma metastatic to the mandible: First case report and review of the literature

Kyu-Young Oh, Seong-Doo Hong

Publication date 08-05-2022


Unlike other soft tissue sarcomas, myxoid liposarcoma tends to metastasize to bone even before developing lung metastases. In this report, we present a unique case of myxoid liposarcoma metastatic to the mandible. A 40-year-old male who had a history of myxoid liposarcoma in the buttock presented with paresthesia in the left lower face and mandible. Radiographic examination revealed an ill-defined radiolucent lesion with cortical destruction in the left mandibular body and ramus. Histopathological examination showed a mixture of small lipoblasts and round primitive mesenchymal cells in a myxoid stroma. Hypercellular areas comprising high-grade round cells were frequently found. The final diagnosis of metastatic myxoid liposarcoma was made. Despite postoperative chemoradiotherapy, further metastases occurred in the lungs and liver, and the patient died of the tumor 23 months after the treatment of the mandibular lesion. This is the first report of myxoid liposarcoma metastatic to the jaw, which may help in the differential diagnosis of intraosseous myxoid tumors of the jaws and highlights unfavorable clinical outcome of metastatic high-grade myxoid liposarcoma.

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GLI1 amplified/fused mesenchymal tumor: A case report and review of the literature

Yuanyuan Liu, Jin Huang, Jingjing Sun, Mingqin Su, Dong Yang, Min Zhao, Qing Huang

Publication date 06-05-2022


Glioma-associated oncogene homologue 1 (GLI1) is an important transcription factor downstream of Hedgehog (HH) signaling pathway, and can be used as a marker of HH signaling pathway activation. GLI1 gene translocations have been reported in several tumor types, including those associated with t(7;12) translocated dermatocytoma, plexus fibromyxoma, and gastroblastoma and other types of malignant soft tissue tumors, whereas GLI1 amplification is actually very rare in tumors. In this case report, we describe for the first time a tumor in the right mandibular gingiva, which is consistent with GLI1 amplified/fused mesenchymal tumor. The tumor cells are elliptic, polygonal and spindle tumor cells growing into nests and segments, lobulated and occasionally mitotic. The identification of these pathological features can help guide pathologists to make appropriate diagnosis and, if necessary, follow-up molecular tests. Our case has been treated with surgical resection. To date, no recurrence or metastasis has occurred and the prognosis is good.

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Mitophagy: A therapeutic target for oral squamous cell carcinoma

Kannan Balachander, Arumugam Paramasivam

Publication date 04-05-2022


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Strengthening koilocyte as a biomarker of HPV infection: A need of the hour

Sachin C. Sarode, Gargi S. Sarode, Namrata Sengupta

Publication date 04-05-2022


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Base of tongue neuroendocrine carcinoma: A case report

Rebecca Paquin, Brittany Gill, Elizabeth Martin, J. Kenneth Byrd

Publication date 02-05-2022


Neuroendocrine tumors are rare entities in the head and neck and an even more rare entity in the tongue. In this case report, we describe a calcified neuroendocrine tumor of the base of tongue that was presumed to be benign and was electively excised with pathology demonstrating low-grade carcinoma with focal neuroendocrine features and extensive ossification. We then discuss the histopathology and management.

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A critical analysis of the classifications of squamous cell carcinoma of the nasal vestibule

Fabio Ferreli, Francesca Pirola, Davide Di Santo, Armando De Virgilio, Giuseppe Spriano, Giuseppe Mercante

Publication date 02-05-2022


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miR-185 and its anti-miR as a biomarker and therapeutic target for oral cancer

Durairaj Sekar, Mani Panagal, Dharmar Manimaran, Naushad Ahmad, Tentu Nageswara Rao, Suliman Yousef Alomar

Publication date 26-04-2022


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Inferior outcomes associated with emergency department presentation for head and neck cancer surgery☆

James A. Gallogly, Alizabeth K. Weber, Angela L. Mazul, Jennifer V. Brinkmeier, Sean T. Massa

Publication date 04-05-2022


Head and neck cancer (HNC) patients frequently require care through emergency departments (ED) due to lack of access or symptom acuity, however, the frequency and implications of this occurrence have not been delineated. To determine the association between emergency department admission of HNC surgery with length of stay (LOS) and total costs (TC). A cohort of 12,920 adult HNC patients admitted to acute care hospitals receiving ablative surgery during index admission was identified using the New York State Inpatient Database from 2006 to 2016. Outcomes included LOS, TC, 90-day complications, and inpatient mortality. Eight percent of the cohort was admitted through the ED, which increased over the study period from 6.52% (95% CI: 5.05-7.99) to 17.0% (95% CI: 14.9-19.1). ED admission was associated with a longer LOS (11 days longer, 95% CI 10.3-11.7) and higher mean TC ($43,197) versus non-ED admission ($19,010), with a mean difference of $24,191 (95% CI 20,713-27,669). After controlling for covariates, ED admission was associated with an 81.6% (95% CI 76.8-86.5) and 80.4% (95% CI 70.5-90.8) increase in LOS and TC, respectively, and decreased survival with a hazard ratio of 1.97 (95% CI 1.60-2.42). Rates of ED admission for HNC diagnoses requiring surgical intervention during index admission are rising and associated with longer LOS higher TC, more postoperative complications, and increased inpatient mortality after accounting for patient and facility differences. Striving for high-quality HNC cancer care demands addressing barriers to care that contribute to patients relying on the ED for access.

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The impact of physician’s characteristics on decision-making in head and neck oncology: Results of a national survey

Emilien Chabrillac, Sébastien Lamy, Pascale Grosclaude, Fanny Cros, Benjamin Vairel, Jérôme Sarini, Sébastien Vergez, Antoine Nebout, Pierre Bories, Agnès Dupret-Bories

Publication date 03-05-2022


The aim of this study was to identify the socio-professional and behavioral factors influencing decision-making between surgical and non-surgical treatment in Upper Aero Digestive Tract (UADT) oncology among surgeons and oncologists. We conducted a nationwide online survey among surgeons and medical or radiation oncologists treating head and neck cancer patients in France. The questionnaire collected physicians' demographics, type of practice, individual behavioral characteristics (attitudes toward risk and uncertainty) and data on decision-making via clinical case scenarios. In total, 197 questionnaires were usable. Clinical case scenarios were grouped into three categories according to the prognostic and functional impact of the choice between surgical or non-surgical treatment. For clinical case scenarios where evidence-based medicine considered surgery as the best option, surgeons were significantly more likely to offer surgery in multivariable analysis. When surgery and non-surgical treatment were equivalent, multivariable analysis showed that the tendency to offer surgery increased with the physician's age, and decreased as the number of patients treated per year increased. When non-surgical treatment was the best option because of very high surgical morbidity, multivariable analysis showed a higher propensity to opt for surgery for the age group 40 - 59 versus 25 - 39, and a lower likelihood of choosing surgery among oncologists. This study sheds light on the physicians' socio-professional and behavioral factors influencing decision-making in UADT oncology. These mechanisms, poorly studied and probably underestimated, partly explain the variability of the decisions taken when confronted with clinical situations that are subject to debate.
gov ID: NCT03663985.

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Pembrolizumab with or without chemotherapy versus cetuximab plus chemotherapy to treat recurrent or metastatic head and neck squamous cell carcinoma: An updated KEYNOTE-048 based cost-effectiveness analysis

Longjiang She, Kun Tian, Jiaqi Han, Weihan Zuo, Zhu Wang, Ning Zhang

Publication date 29-04-2022


Recently, updated data from KEYNOTE-048 revealed that pembrolizumab with or without chemotherapy could improve progression-free survival (PFS)2 compared with cetuximab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). A Markov structure was conducted to evaluate the cost and effectiveness of pembrolizumab monotherapy or pembrolizumab plus chemotherapy vs. cetuximab plus chemotherapy in the first-line treatment of recurrent or metastatic HNSCC from the United States payer's perspective. Total cost, health outcomes, and incremental cost-effective ratios (ICERs) were estimated. Additional analyses were conducted in the total population and in two different programmed cell death 1 ligand 1 (PD-L1) combined positive scores (CPSs) (≥1 and ≥ 20) population. Sensitivity analysis were used to test the stability of the model. When compared with cetuximab plus chemotherapy, the pembrolizumab monotherapy strategy was dominated by lower cost and better efficacy in all three populations. The incremental costs and quality adjusted life years (QALYs) yielded by pembrolizumab plus chemotherapy compared with cetuximab plus chemotherapy were $16016.88 and 0.11 in the total population, and $24467.47 and 0.18 and $30448.46 and 0.20 in the populations with a PD-L1 CPS ≥ 1 and CPS ≥ 20, respectively, leading to ICERs of $147876.14, $134237.84, and $153660.78 per QALY, respectively. First-line treatment with pembrolizumab or pembrolizumab plus chemotherapy are cost-effective strategies compared with cetuximab plus chemotherapy when the value of willingness-to-pay (WTP) was $150000 per QALY for the total and PD-L1 CPS ≥ 1 populations with recurrent or metastatic HNSCC.

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Discrepancy between subjective and objective postoperative oral dysfunction assessment after oral cancer treatment: A single-center cross-sectional study

Akira Kato, Yuhei Matsuda, Reon Morioka, Tatsuo Okui, Satoe Okuma, Hiroto Tatsumi, Takahiro Kanno

Publication date 29-04-2022


It has been reported that in many cancer types, the evaluation of complications and side effects of treatment differs between subjective and objective evaluations. The purpose of this study is to verify whether the evaluation of postoperative oral dysfunction following oral cancer treatment was consistent subjective and objective evaluations. This cross-sectional study collected background data and evaluated the oral function (microorganisms, oral dryness, occlusal force, tongue pressure, masticatory function and eating assessment tool [EAT-10]) of 75 patients from September 2019 to December 2021. The postoperative oral dysfunction-10 (POD-10) was used for the subjective assessment of dysfunction in oral cancer patients. Also, Matsuda-Kanno classification was used for the objective assessment. The kappa coefficient between POD-10 and oral dysfunction was calculated for the degree of agreement. The relationship between oral function measurements and POD-10 was examined by multiple regression analysis. The patients' median age was 72.0 (25-75 percentile: 64.0-78.0) and 69.3% were male. The kappa coefficients indicating the degree of agreement with POD-10 were 0.41 (P < 0.01) for occlusal force, 0.27 (P = 0.01) for masticatory function, and 0.59 (P < 0.01) for EAT-10. Multiple regression analysis showed a significant association of occlusal force (β = -0.33, P = 0.03) and EAT-10 (β = 0.80, P < 0.01) with POD-10. For postoperative oral dysfunction type III (occlusal type), the evaluations of subjective and objective evaluations tended to be consistent. However, for type I (transport type) and II (oral hygiene type), these evaluations may be prone to overestimation or underestimation by either the medical professional or the patient.

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Engineering a single-chain variable fragment of cetuximab for CAR T-cell therapy against head and neck squamous cell carcinomas

Corinna Haist, Zoe Poschinski, Arthur Bister, Michèle J. Hoffmann, Camilla M. Grunewald, Alexandra Hamacher, Matthias Kassack, Constanze Wiek, Kathrin Scheckenbach, Helmut Hanenberg

Publication date 26-04-2022


The monoclonal antibody cetuximab recognizes domain III of the epithelial growth factor receptor (EGFR) with high-affinity and is an important element in the treatment of several malignancies that overexpress non-mutated wild-type EGFR. In order to create an EGFR recognizing chimeric antigen receptor (CAR) for cellular immunotherapy of head and neck squamous cell carcinoma (HNSCC), we rationally designed single chain fragments of different lengths based on the cetuximab variable heavy and light chains. We then cloned the different cetuximab fragments into our second generation CAR construct, expressed CARs on primary human T-cells from healthy donors using mono- or biscistronic lentiviral vectors and tested the stability, functionality and specificity of the CARs. Our smallest CAR construct was most efficient with greatly improved vector production and T-cell transduction efficacy. Finally, we demonstrated that the new cetuximab CAR construct expressed on T-cells is highly reactive against EGFR-positive HNSCCs and also malignant cells from other solid cancer entities. In conclusion, we generated an optimized high-affinity EGFR CAR construct for the next steps in cancer immunotherapy, which need to focus on the development of armored CAR T-cells that will be more resistant and effective in the hostile microenvironment present in solid cancers.

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CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma

Tianyang Liu, Lin Ma, Lianhao Song, Bingqing Yan, Siwei Zhang, Bozhi Wang, Nan Zuo, Xinlei Sun, Yongqiang Deng, Qiushi Ren, Yujun Li, Jingsong Zhou, Qi Liu, Lanlan Wei

Publication date 25-04-2022


This study aims to investigate how human papillomavirus (HPV) affects the key gene in the biological behaviors of head and neck squamous cell carcinoma (HNSCC) that leads to better response to radiotherapy. The expression of key gene CENPM was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data and HPV positive and HPV negative HNSCC tumors and cells. Assays with siRNAs, CRISPR/Cas9-based models, Western blot, qRT-PCR, ChIP, etc., were used to explore how HPV affects CENPM and response to radiotherapy for HNSCC. CENPM occupies the hub in the HPV-related gene network. HPV-positive HNSCC showed higher level of CENPM expression comparing with HPV-negative HNSCC. HPV E5 has the most pronounced impact on CENPM (R = 0.44, p = 0.00081). This might result from the binding of transcription factor E2F1 to CENPM. We further found that inhibition of CENPM expression in HPV-positive HNSCC cell line SCC47 increased resistance to X-ray radiation by approximately 59% under 2 Gy irradiation, which may be resulted from a reduced proportion of mitotic cells. HPV E5 enhances CENPM expression by transcription factor E2F1 in HNSCC, which results in a radiosensitive profile in cell cycle redistribution of HNSCC. Thus, HPV infection in HNSCC provides profound evidence that underscores the magnitude of E2F1 control of CENPM expression illustrating the potential clinical benefit of CENPM examination for difficult-to-treat HPV-negative cancers.

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Head and neck radiotherapy-induced carotid toxicity: Pathophysiological concepts and clinical syndromes

Alexandre Leboucher, Sandrine Sotton, Isabelle Gambin Flandrin, Nicolas Magné

Publication date 06-05-2022


This review aims at offering a concise cross-section of head and neck radiotherapy-induced carotid toxicity for pathological concepts to emerge and become part of clinical routine. Radiation-induced carotid toxicities such as atherosclerosis, arterial stiffness and arterioradionecrosis result from radiation dose limitation. Atherosclerosis is related to lesions in the epithelial wall. Such lesions are early radiotherapy-related toxicities and depend on the radiation dose. Atherosclerosis may lead to carotid stenosis and stroke. Arterial stiffness and arterioradionecrosis are late toxicities of the connective tissue that have a low alpha/beta ratio. They are risk factors of pseudoaneurysm and carotid blowout syndrome or stroke in some cases. Because all these pathophysiological mechanisms interfere, post-radiation vascular diseases remain particularly severe and difficult to understand.

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Effectiveness of topical fluorides in prevention of radiation caries in adults: A systematic review and meta- analysis

Deepali Agarwal, Bharathi Purohit, Priyanka Ravi, Harsh Priya, Vijay Kumar

Publication date 29-04-2022


Topical fluoride is used for prevention of dental caries. However, its effectiveness and more specifically its formulation and frequency of application in patients undergoing head and neck radiotherapy are still debatable. The aim of this systematic review was to pool the evidence of effectiveness of various topical fluorides in preventing radiation caries or change in bacterial growth in adult patients of head and neck cancer. Three databases (Pub Med and Google Scholar and Cochrane) were searched for randomized controlled or uncontrolled trials or quasi randomised trials published till February 2021. Two independent reviewers screened 346 abstracts finally 14 articles were included in the current systematic review. Primary outcome evaluated was the prevention of radiation caries or change in bacterial growth in saliva. Meta-analysis was performed for the sub groups formed on the basis of fluoride formulations and adjuncts used with it. Studies included were highly heterogeneous. Majority of studies found different fluoride formulations to be effective in controlling radiation caries to a variable extent up to 70% depending upon the intervention, patient compliance, rate of attrition and follow up period. Sodium fluoride was the most commonly used caries preventive agent. Meta-analysis showed no significant difference between sodium fluoride formulations and other fluoride agents. Fluoride treatment when incorporated with re-mineralising agent had no significant effect on caries prevention CONCLUSION: Fluoride prevents radiation caries. However, to delineate its exact formulation, dosage or frequency, there is need for more well conducted randomised controlled trials.

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MicroRNA-138 and its targets: A therapeutic molecule for oral squamous cell carcinoma

Sushmaa Chandralekha Selvakumar, Preethi K.Auxzilia, Y. Dinesh, M. Senthilmurugan, Durairaj Sekar

Publication date 24-05-2022


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