The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade.

BACKGROUND: Never-smokers and never-drinkers patients (NSND) suffering from oral squamous cell carcinoma (OSCC) are epidemiologically different from smokers drinkers (SD). We therefore hypothesized that they harbored distinct targetable molecular alterations. PATIENTS AND METHODS: Data from The Cancer Genome Atlas (TCGA) (discovery set), Gene Expression Omnibus and Centre Léon Bérard (CLB) (three validation sets) with available gene expression profiles of HPV-negative OSCC from NSND and SD were mined. Protein expression profiles and genomic alterations were also analyzed from TCGA, and a functional pathway enrichment analysis was carried out. Formalin-fixed paraffin-embedded samples from 44 OSCC including 20 NSND and 24 SD treated at CLB were retrospectively collected to perform targeted-sequencing of 2559 transcripts (HTG EdgeSeq system), and CD3, CD4, CD8, IDO1, and PD-L1 expression analyses by immunohistochemistry (IHC). Enrichment of a six-gene interferon-γ signature of clinical response to pembrozulimab (PD-1 inhibitor) was evaluated in each sample from all cohorts, using the single sample gene set enrichment analysis method. RESULTS: A total of 854 genes and 29 proteins were found to be differentially expressed between NSND and SD in TCGA. Functional pathway analysis highlighted an overall enrichment for immune-related pathways in OSCC from NSND, especially involving T-cell activation. Interferon-γ response and PD1 signaling were strongly enriched in NSND. IDO1 and PD-L1 were overexpressed and the score of response to pembrolizumab was higher in NSND than in SD, although the mutational load was lower in NSND. IHC analyses in the CLB cohort evidenced IDO1 and PD-L1 overexpression in tumor cells that was associated with a higher rate of tumor-infiltrating T-cells in NSND compared with SD. CONCLUSION: The main biological and actionable difference between OSCC from NSND and SD lies in the immune microenvironment, suggesting a higher clinical benefit of PD-L1 and IDO1 inhibition in OSCC from NSND.

[Harvesting technique of chimeric multiple paddles fibular flap for wide oromandibular defects]. / Technique de prélèvement du lambeau de fibula chimérique multipalettes pour la reconstruction des larges defects oromandibulaires.

Carcinological head and neck reconstruction still remains a challenge due to the volume and varied tissues needed. Large and wide oromandibular defects require, not just the bone but also soft tissues for the pelvilingual reconstruction and therefore, a second free flap may become necessary in addition to a fibular flap. The option of an unique chimeric flap based on the fibular artery and its branches is less known whereas it offers the advantage of a unique flap with bone, muscle and multiple skin paddles, independent of each other. The aim of this technical note is to present step by step the surgical procedure of this chimeric flap and share this method that avoids a second free flap.

Modification of the pedicled osteomuscular dorsal scapula flap to include a skin paddle.

This article describes a reliable surgical alternative for the repair of wide oromandibular defects that require bone and soft tissues, which was applied in two patient cases. While microvascular free flap transfer, especially the fibula flap, is the gold standard for mandibular reconstruction, this reconstruction is challenging in patients with a vessel-depleted neck and/or severe arteriosclerosis. The pedicled osteomuscular dorsal scapular (OMDS) flap is a surgical alternative to free flap transfer in this clinical setting. The technique described involves harvesting of the OMDS flap to include a skin paddle, which is often required to close wide oral mucosal defects.

The promising impact of molecular profiling on treatment strategies in oral cancers.

Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality. Although OSCC may develop from easily accessible oral preneoplastic lesions (OPLs), no intervention has been reported so far that reduces the rate of malignant transformation. A comprehensive molecular characterization of oral carcinogenesis may help refining treatment strategies both in patients with OPLs and OSCC. Herein, we review main molecular alterations occurring at different steps during oral carcinogenesis and show how molecularly-based medicine and surgery may impact the outcome of OSCC in the future.

'Canalization' of the frontal sinus: a functional approach for the management of post-traumatic sinusitis with lateral bony septa. Report of two cases and long-term follow-up.

The patency of the naso-frontal duct is a key issue in the surgical management of chronic frontal sinusitis. Most of the current operative techniques only provide access to the paramedian portions of the frontal sinus. A canalization approach that allows a functional frontal sinus to be maintained while providing good access to the most lateral areas of the sinus is described herein. Two cases of severe post-traumatic frontal sinusitis, operated on successfully by canalization method based on the conservation of the frontal sinus and the maintenance of the patency of the naso-frontal duct, using both open and endonasal approaches, are reported. One patient was followed-up for 8 years and the other for 7 months. Canalization requires validation in a larger series. This approach provides an alternative to both cranialization and strictly endoscopic methods in lateralized frontal sinus retentions and allows mucocele to be avoided.