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Introduction: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours., Methods: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors., Results: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis., Conclusion: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PS is a member of HTG Diagnostics Scientific Advisory Board and receives research grants from HTG Diagnostics, Inivata, ArcherDx, Bristol-Myers Squibb, Roche Molecular Diagnostics, Roche, AstraZeneca, Novartis, Bristol-Myers Squibb Foundation and Illumina; JF reports grants, personal fees and non-financial support from Bristol-Myers Squibb, personal fees and non-financial support from MSD, personal fees from Merck, personal fees and non-financial support from Astrazeneca, personal fees from Rakuten, personal fees from Biogen and personal fees from Innate Pharma; SL received advisory board honoraria from AbbVie, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp and Dohme, Takeda, Roche/Genentech; FG reports personal grants consultancy for Roche, AstraZeneca, and payments for development of educational presentations for Roche, Servier, Amgen, Merck. All remaining authors have declared no conflicts of interest., (© 2022 The Authors.)

A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Many neoplasms remain unclassified after histopathological examination, which requires further molecular analysis. To this regard, mesenchymal neoplasms are particularly challenging due to the combination of their rarity and the large number of subtypes, and many entities still lack robust diagnostic hallmarks. RNA transcriptomic profiles have proven to be a reliable basis for the classification of previously unclassified tumors and notably for mesenchymal neoplasms. Using exome-based RNA capture sequencing on more than 5000 samples of archival material (formalin-fixed, paraffin-embedded), the combination of expression profiles analyzes (including several clustering methods), fusion genes, and small nucleotide variations has been developed at the Centre Léon Bérard (CLB) in Lyon for the molecular diagnosis of challenging neoplasms and the discovery of new entities. The molecular basis of the technique, the protocol, and the bioinformatics algorithms used are described herein, as well as its advantages and limitations., (© 2022 Wiley Periodicals LLC.)

Background: Programmed death-ligand 1 (PD-L1) is the most validated predictive biomarker used for the treatment of head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (ICI). Several gene expression-based signatures surrogate of the activation of IFN-gamma pathway and of the presence of tertiary lymphoid structures (TLS) have also been proposed as potential biomarkers. While they may have a potential therapeutic implication, the longitudinal changes of either PD-L1 or gene expression profiles between the initial and recurrent HNSCC lesions is unknown., Methods: PD-L1 immunohistochemistry (IHC) and targeted RNA-sequencing of 2,549 transcripts were analyzed on paired specimens from the initial diagnosis and recurrent HNSCC. PD-L1 status was defined using the combined positive score (CPS). PD-L1 mRNA levels were compared with protein expression levels by IHC. Enrichment scores of surrogate signatures for TLS and IFN-gamma (IFN-γ) pathway activation were computed using the single sample gene set enrichment analysis (ssGSEA)., Results: PD-L1 status was 64% (21/33) concordant between the initial and recurrent lesions using a CPS 1 threshold and 67% (22/33) concordant using a CPS 20 threshold. CPS score was associated with PD-L1 gene expression levels. There was a 43% (15/35) and 66% (23/35) concordance for the IFN-γ and TLS signature scores, respectively., Conclusion: Our study reveals temporal heterogeneity of PD-L1 status and TLS/IFN-γ gene expression surrogates in HNSCC that need to be considered when interpreting biomarker studies., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hyperprogressive disease (HPD) rate in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI) was determined using tumor growth kinetics (TGK) and compared with rapidly progressive screen-failure (SF) patients. The impact of TGK on outcomes with salvage chemotherapy (SCT) was also evaluated. Results: HPD was found in 22/120 (18%) patients. Median TGK before the onset of immunotherapy (TGK pre ) was 2.7 for SF patients and 4.8 for HPD patients, with no significant difference ( p = 0.17). Disease control rate after initial progressive disease on ICI was 86% with SCT in case of tumor growth deceleration vs 39% in case of tumor growth acceleration. Conclusions: HPD was frequent, but TGK of HPD patients treated with ICI did not differ from SF patients, suggesting that there is no relevant causal relationship between HPD and ICI. After initial PD with ICI, tumor growth deceleration was associated with better outcomes, indicating that TGK R might be useful to detect late responders, meriting prospective investigations. Materials and Methods: TGK ratio (TGK R ) was defined as the ratio of TGK on ICI (TGK post ) to TGK pre . HPD was defined as TGK R ≥ 2. TGK R >1 indicated tumor growth acceleration, while 0 < TGK R < 1 indicated tumor deceleration., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest., (Copyright: © 2020 Karabajakian et al.)

Background: We compared the outcome of postoperative unilateral cervical nodes radiotherapy (UL-RT) vs bilateral cervical nodes plus total mucosal irradiation (COMP-RT) in the management of head and neck carcinoma of unknown primary (HNCUP)., Methods: HNCUP, defined by the absence of primary despite a PET-CT combined with a panendoscopy, were treated with curative intent by initial ipsilateral neck dissection. Sixty-nine patients with unilateral HNCUP were included: 23 received UL-RT while 46 received COMP-RT. Carcinologic outcomes and long-term quality of life (QOL) according to the QOL Questionnaire for Head and Neck 35 were assessed., Results: Within 6.3 years of median follow-up, there was no significant difference in primary tumor emergence rate (P = .68), cervical node recurrence rate (P = .34), or overall survival (P = .33) between UL-RT and COMP-RT groups. A trend toward QOL improvement was observed in the UL-RT group., Conclusion: UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP management., (© 2019 Wiley Periodicals, Inc.)

Keratocystic odontogenic tumors (KCOT) are exceptional in children and adolescents as they usually occur in the third decade. The present study reports the case of a 15 years old girl who was diagnosed with a KCOT that underwent malignant transformation. KCOT diagnostic was based on clinical, radiological, histopathological and immunohistochemical findings. A conservative treatment by enucleation was performed. Histopathological analysis of the surgical specimen concluded to a KCOT, with an infra-centimetric focus of well-differentiated squamous cell carcinoma. Owing to the well-differentiated character of the squamous cell carcinoma, a single clinical and MRI surveillance every 3 months was decided, without complementary treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The paraganglioma is a rare tumour that can sometimes develop near to the pancreatic gland and can occasionally mimic an intra pancreatic mass. Invasive investigations with puncture or primary surgical resection must be avoided because of the risk of vital complications., Exegesis: We report on the case of a 41 years old woman presenting with a mass apparently affecting the pancreatic gland. She also presented with malaises. Paraganglioma was suspected because of the malaises and the blood pressure crises. The diagnosis was permitted by the findings of high urinary metanephrine levels. So the tumour was resected without previous fine needle aspiration and with specific anaesthetic measures. No complication was observed., Conclusion: When a patient presents with a pancreatic mass, physician must carefully take into account the possibility of a paraganglioma particularly when malaises are present.

The authors report two new cases of inflammatory pseudotumours, sited in the pharynx and neck--sites in which no previous cases have so far been reported in the literature. The aetiology and clinical course of these rare benign tumours remain little understood even today. Their treatment is also not clearly described. This is most often surgical, although medical treatment is often very effective, and is sometimes appropriate. The authors begin by describing these two clinical cases, and then use the literature to give an account of the clinical course and treatment of inflammatory pseudotumours.