Uncovering the WWTR1::NCOA2 Gene fusion in low-grade myoepithelial-rich neoplasm with HMGA2 expression: A case report.

We describe a case of a pleomorphic adenoma (PA) arising from the para-tracheal accessory salivary gland in a 44-year-old male harboring a novel WWTR1::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in salivary gland tumors. The patient presented with hoarseness of voice. The radiological exam revealed a mass in the upper third of the trachea involving the larynx. Histologically, the tumor consisted of bland-looking monocellular eosinophilic epithelial cells arranged in cords and sheets separated by thin fibrous stroma, focally forming a pseudo-tubular pattern. In immunohistochemistry, the tumor cells demonstrated positivity for CK7, PS100, SOX10, and HMGA2; and negativity for CK5/6, p40 p63, and PLAG1. In addition, the clustering analysis clearly demonstrates a clustering of tumors within the PA group. In addition to reporting this novel fusion in the PA spectrum, we discuss the relevant differential diagnoses and briefly review of NCOA2 and WWTR1 gene functions in normal and neoplastic contexts.

Investigating oral somatosensory perception and oral symptoms of head and neck cancer patients: insights on eating behaviour.

PURPOSE: Sensory alterations and oral manifestations are prevalent among head and neck cancer (HNC) patients. While taste and smell alterations have been thoroughly investigated, studies on their oral somatosensory perception remain limited. Building upon our previous publication that primarily focused on objective somatosensory measurements, the present work examined self-reported sensory perception, including somatosensation and oral symptoms, in HNC patients and evaluated their link with eating behaviour. METHODS: A cross-sectional study was conducted using self-reported questionnaires on sensory perception, oral symptoms, sensory-related food preference, and eating behaviour among HNC patients (n = 30). Hierarchical clustering analysis was performed to categorise patients based on their sensory perception. Correlations between oral symptoms score, sensory perception, sensory-related food preference, and eating behaviour were explored. RESULTS: Two distinct sensory profiles of patients were identified: no alteration (n = 14) and alteration (n = 16) group. The alteration group showed decreased preference towards several sensory modalities, especially the somatosensory. Concerning eating behaviour, more patients in the alteration group agreed to negatively connotated statements (e.g. having food aversion and eating smaller portions), demonstrating greater eating difficulties. In addition, several oral symptoms related to salivary dysfunction were reported. These oral symptoms were correlated with sensory perception, sensory-related food preference, and eating behaviour. CONCLUSION: This study presented evidence demonstrating that sensory alterations in HNC patients are not limited to taste and smell but cover somatosensory perception and are linked to various aspects of eating. Moreover, patients reported experiencing several oral symptoms. Those with sensory alterations and oral symptoms experienced more eating difficulties.

Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2.

AIMS: Salivary gland neoplasms (SGN) exhibiting the HMGA2::WIF1 fusion are recognized by their resemblance to histology found in canalicular adenoma. Recently, ~20% of cases among 28 HMGA2::WIF1-rearranged-SGN showed malignancy and adverse outcomes (recurrence, distant metastasis, and disease-specific mortality). Among them, MDM2/CDK4 amplifications were identified in one case. This outcome suggests that the MDM2/CDK4 amplifications could be useful to predict an aggressive course of carcinoma ex-pleomorphic adenoma (CEPA). METHODS AND RESULTS: We investigated the correlation between HMGA2 fusion and MDM2 amplification in four salivary gland neoplasms, providing detailed clinicopathological features and outcomes. Cases were selected from different institutions. Histological examination, immunohistochemistry, fluorescence in situ hybridization (FISH), RNA sequencing, and whole-exome capture were performed. The cohort included four CEPA cases, all female, aged between 32 and 89 years. Tumours arose from the parotid gland with an average size of 24.5 mm. None exhibited recurrence or distant metastases during the 4-5 months of follow-up. Pathologically, all cases displayed a peculiar atypical nuclei with 'gear-like appearance'. Immunohistochemically, tumours exhibited a biphasic pattern with myoepithelial and ductal differentiation markers. All cases showed HMGA2 overexpression and MDM2 amplification by FISH and RNA sequencing. In a control cohort of MDM2 nonamplified CEPA cases, not exhibiting the peculiar nuclear atypia. CONCLUSIONS: Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Carcinomas of the external auditory canal: Management and results: A multicenter REFCOR propensity score matching study.

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.

Functional or radical surgical treatment of laryngeal chondrosarcoma, analysis of survival and prognostic factors: A REFCOR and NetSarc-ResOs multicenter study of 74 cases.

INTRODUCTION: Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL. MATERIALS AND METHODS: A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients. RESULTS: 74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI [57.5-83.4]) and the 5-year TLFS was 61.7 % (95 % CI [50.4-75.5]). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % [1.61-7.92] p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % [1.64-15.67] p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % [1.17-23.6] p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % [1.04-6.45] p = 0.03). CONCLUSION: These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.

Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Transoral Laser Microsurgery versus Robot-Assisted Surgery for Squamous Cell Carcinoma of the Tongue Base (Oncological and Functional Results)-A Retrospective GETTEC Multicenter Study.

The base of the tongue (BOT) is the second most common site for squamous cell carcinoma (SCC) in the oropharynx. There are currently no clear guidelines for the management of BOT SCC. Our main objective was to compare the oncological outcomes of two minimally invasive approaches, transoral laser microsurgery (TLM) and transoral robot-assisted surgery (TORS). This was a retrospective French GETTEC (Groupe d'Études des Tumeurs de la Tête et du Cou) multicenter study of patients with BOT SCC removed surgically either by TLM or TORS between 2005 and 2021. The study group included 16 patients treated by TLM and 38 by TORS, with median follow-up times of 14.4 and 37.2 months, respectively. The overall survival (OS) rates at 2 and 3 years were 67% in the TLM group and 90% at 2 years and 86% at 3 years in the TORS group (p = 0.42, p = 0.20). There was no significant difference in recurrence-free survival (RFS) between the two techniques after 2 and 3 years. The tumors removed by TORS were significantly larger. Operative times were significantly shorter in the TLM group. There were no differences in feeding resumption; none of the patients in the TLM group required a tracheotomy. Postoperative hemorrhagic complication rates were similar in the two groups (12% for TLM and 13% for TORS). Both TORS and TLM showed encouraging oncological, functional, and safety results in BOT SCC even in recurrence or second primary cancer patients, without a technique being found superior in terms of OS or RFS. Tumors removed by TORS were larger without an increase in postoperative bleeding, extending the possibilities of transoral treatment.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients.

BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.

A New Animal Model of Laryngeal Transplantation.

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

Resection and reconstruction of the carotid artery for head and neck squamous cell carcinoma: a GETTEC study.

OBJECTIVES: Main: To describe 1-year overall survival (OS) after primary or salvage management of head and neck squamous cell carcinoma (HNSCC) invading the common or internal carotid artery (CCA/ICA). Secondary: To assess disease control rate, treatment morbidity, and radio-anatomopathologic correlation. METHODS: Retrospective study of 67 patients, treated between 1999 and 2020 for N3bM0 HNSCC invading the CCA/ICA as identified by CT-scan. Tumors that could not have been resected with a complete en-bloc resection sacrificing and reconstructing the CCA/ICA were excluded. Patients were separated into two groups (primary or salvage treatment) and studied according to the type of treatment they received: radiotherapy/radiochemotherapy (RT/RCT), surgery, or systemic therapy (ST). RESULTS: For newly treated patients, the 1-year OS was significantly better after RT/RCT (73%) than after surgery (40%, p < 0.0001). In the salvage setting, the 1-year OS after surgery (40%) was better than after ST (14%, statistically suggestive difference with p = 0.0241). Surgery improved cervical control, but distant metastases occurred in more than 50% of cases regardless of treatment. No neurological complication occurred after carotid reconstruction. Perioperative mortality was 7% (1/15). The carotid invasion was confirmed by pathological examination in all five patients with an arterial deformation on CT-scan, in seven among eight patients with CCA/ICA encasement greater than 270°, and in four out of seven patients with CCA/ICA encasement between 180° and 270°. CONCLUSION: Neck dissection with carotid resection and reconstruction is technically feasible with acceptable neurovascular morbidity. For newly treated patients, survival is better after RT/RCT. For salvage treatment, surgery could be proposed to selected patients.

Circulating Tumor Cell Detection during Neoadjuvant Chemotherapy to Predict Early Response in Locally Advanced Oropharyngeal Cancers: A Prospective Pilot Study.

Patients with locally advanced oropharyngeal carcinoma treated with neoadjuvant chemotherapy are reassessed both radiologically and clinically to adapt their treatment after the first cycle. However, some responders show early tumor progression after adjuvant radiotherapy. This cohort study evaluated circulating tumor cells (CTCs) from a population of locally advanced oropharyngeal carcinoma patients treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) induction chemotherapy or DCF with a modified dose and fractioned administration. The counts and phenotypes of CTCs were assessed at baseline and at day 21 of treatment, after isolation using the RosetteSepTM technique based on negative enrichment. At baseline, 6 out of 21 patients had CTCs (28.6%). On day 21, 5 out of 11 patients had CTCs (41.6%). There was no significant difference in the overall and progression-free survival between patients with or without CTCs at baseline (p = 0.44 and 0.78) or day 21 (p = 0.88 and 0.5). Out of the 11 patients tested at day 21, 4 had a positive variation of CTCs (33%). Patients with a positive variation of CTCs display a lower overall survival. Our findings suggest that the variation in the number of CTCs would be a better guide to the management of treatment, with possible early changes in treatment strategy.

CD44, γ-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma.

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

Functional outcomes of soft palate free flap reconstruction following oropharyngeal cancer surgery.

INTRODUCTION: The objective of this study was to assess the impact of surgical resection and free flap reconstruction of soft palate cancer on speech, swallowing and quality of life, and to identify the factors influencing functional outcomes and quality of life. MATERIAL AND METHODS: Patients treated with surgical resection of squamous cell carcinoma and free-flap reconstruction of the soft palate were reviewed at least 12 months after surgery. Speech was assessed using the Hirose intelligibility scoring system, nasalance scoring, GRBAS scoring and the Voice Handicap Index 30 (VHI30) questionnaire. Swallowing was assessed by fiberoptic endoscopy and the Deglutition Handicap Index (DHI). Quality of life was assessed using EORTC QLQ-C30 and QLQ-H&N35 questionnaires. RESULTS: 29 patients were included. Speech outcomes were satisfactory, demonstrating normal or slightly below normal speech intelligibility in 75.9% of the patients, moderate or no rhinolalia in 72.4% of the patients and mean overall VHI30 scores indicative of slight or no handicap in 86.2% of the patients. Swallowing outcomes were satisfactory, with mean overall DHI scores indicative of slight or no handicap in 82.8% of the patients. Patient quality of life was preserved as demonstrated by mean quality of life and functioning scales scores all superior to 80%. CONCLUSION: The sequelae arising from surgical resection and free-flap reconstruction of soft palate cancer are tolerable, involving slight handicap in terms of speech and swallowing and relatively little impact on quality of life.

History of tonsillectomy and risk of oropharyngeal cancer.

OBJECTIVE: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). MATERIALS AND METHODS: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference. RESULTS: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results. CONCLUSION: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.

Influence of postoperative radiotherapy target volumes in unilateral head and neck carcinoma of unknown primary: A multicentric study using propensity score.

OBJECTIVE: To compare the impact of two radiation modalities on loco-regional control, survival and tumour emergence, after node dissection for an unilateral head and neck carcinoma of unknown primary (HNCUP). MATERIALS AND METHODS: This is a multicentric retrospective study of 138 patients with unilateral HNCUP treated between 2002 and 2017. The absence of primary tumour was assessed by a systematic panendoscopy and positron emission tomography. Neck dissection was initially performed for all patients. Radiation Therapy was delivered on ipsilateral lymph node areas in 62 cases (44%: UL-RT group) and on bilateral lymph node areas and the entire pharyngeal mucosa in 77 cases (56%: COMP-RT group). Impact of radiation modalities on locoregional control and overall survival was assessed using propensity score matching method in order to balance baseline characteristics between the two groups. RESULTS: The population included 80.4% men, 80.4% smokers, 32.6% P16 positive tumours and 71.0% extracapsular extension. After a median follow-up of 5 years, the locoregional control rate was 80.3% in the UL-RT group and 75.3% in the COMP-RT group (p = 0.688). The corresponding rate of contralateral lymph node recurrence was 0% versus 2.6% (p = 0.503) and the rate of tumour emergence was 11.5% versus 9.1% (p = 0.778). No significant difference was observed between the UL-RT and the COMP-RT groups for overall survival (p = 0.9516), specific survival (p = 0.4837) or tumour emergence (p = 0.9034). CONCLUSION: UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP post-operative management.

Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status.

AIMS: Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5-20% of p16-positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC-related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV-driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC. METHODS AND RESULTS: A total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16-positive or p16-negative/wild-type patterns-p53 (WT-p53) cases (n = 63), DNA in-situ hybridisation for high-risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (n = 19). A significant association between TP53 mutation and pattern of p53 expression was found (WT-p53, seven of 16, P < 0.001). The p16-positive/WT-p53 was significantly associated with HPV+ tumour status (p16-positive/WT-p53, 50 of 110, P < 0.001). Interestingly, a subset of p16-positive OPSCC was unrelated to HPV (13.5%, eight of 59), and showed mutant-type staining of p53 expression. CONCLUSIONS: The p16 protein immunopositivity in conjunction with the mutant-type pattern of p53 staining helped to reclassify a subset of p16-positive OPSCC as OPSCC-unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.

Impact of the First Wave of the COVID-19 Pandemic on the Lyon University Hospital Cancer Institute (IC-HCL).

This article presents the protective measures put in place at the "Institut de Cancérologie des Hospices de Lyon" (IC-HCL) during the first wave of the COVID-19 pandemic in France (spring 2020) and how they impacted IC-HCL clinical activity. Spring 2020 activities were compared to winter 2019-2020. Results showed a decrease of activity of 9% for treatment dispensations, 17% for multidisciplinary team meetings, 20% for head and neck and thoracic surgeries, and 58% for new patient enrolment in clinical trials. Characteristics of patients treated for solid cancer and hospitalized for COVID-19 during spring 2020 were collected in a retrospective study. Mortality was attributed to COVID-19 for half of the cases, 82% being patients above 70 and 73% being stage IV. This is in concordance with current findings concluding that the risk of developing severe or critical symptoms of COVID-19 is correlated with factors co-occurring in cancer patients and not to the cancer condition per se. While a number of routines and treatment regimens were changed, there was no major decline in numbers of treatments conducted at the IC-HCL during the first wave of the COVID-19 pandemic that hit France between March and May 2020, except for clinical trials and some surgery activities.