Objective Literature analysis on the prognostic factor of the nodal yield (NY) in neck dissections (NDs), which in general surgical oncology is a strong prognosticator and quality‐of‐care marker. Methods We performed a systematic review of all PubMed and Embase publications until June 30, 2018 screening for data on NY as prognosticator and overall survival (OS) as outcome in patients with head and neck squamous cell carcinoma (HNSCC). Risk for bias was asserted by application of the Quality In Prognosis Studies tool. Results Of the 823 screened publications, 15 were included in this analysis. Five out of seven that compared NY ≥18 vs <18 as prognosticator, showed significantly improved survival if NY ≥18. Six studies used other cutoffs and three reported improved survival with each additionally harvested lymph node. Conclusion Increased NY in ND specimen for HNSCC, most commonly described as ≥18 lymph nodes, is associated with improved OS and could be used as a prognosticator and quality‐of‐care marker.

Background Understanding molecular pathogenesis of head and neck squamous cell carcinomas (HNSCC) has considerably improved in the last decades. As a result, novel therapeutic strategies have evolved, amongst which are epidermal growth factor receptor (EGFR)-targeted therapies. With the exception of cetuximab, targeted therapies for HNSCC have not yet been introduced into clinical practice. One important aspect of new treatment regimes in clinical practice is presence of robust biomarkers predictive for therapy response. Methods We performed a systematic search in PubMed, Embase and the Cochrane library. Articles were included if they investigated a biomarker for targeted therapy in the EGFR-PI3K-AKT-mTOR-pathway. Results Of 83 included articles, 52 were preclinical and 33 were clinical studies (two studies contained both a preclinical and a clinical part). We classified EGFR pathway inhibitor types and investigated the type of biomarker (biomarker on epigenetic, DNA, mRNA or protein level). Conclusion Several EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers have been researched for HNSCC but few of the investigated biomarkers have been adequately confirmed in clinical trials. A more systematic approach is needed to discover proper biomarkers as stratifying patients is essential to prevent unnecessary costs and side effects. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-021-00518-6.

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Background Oral squamous cell carcinoma (OSCC) frequently invades the jaw. The exact mechanism of bone invasion remains unclear. This study investigates the role of osteoclasts and RANKL/OPG/RANK in the development of bone invasion in OSCC. Methods OSCC-patients treated with resection were included and divided in three groups; Non-invasion (NI-group), erosion (E-group) and bone invasion (I-group). Tissue-sections were stained with Cathepsin K (for counting osteoclasts), RANKL, OPG and RANK. Staining intensity was scored in tumor-front, tumor-center, tumor-backside and normal mucosa. Immunohistochemistry and qPCR for RANKL/OPG/RANK was performed in five head-and-neck SCC organoids to correlate protein and mRNA-expression levels. Results The mean number of osteoclasts in Cathepsin K stained sections in the NI-group was 3.09 (1.12-5.05; 95%CI), in the E-group 6.15 (4.04–8.25; 95%CI) and in the I-group 10.58 (5.81–15.34; 95%CI). Compared to normal mucosa, the expression in all tumor regions was higher for RANKL, in most tumor regions for OPG and not higher for RANK. RANKL-expression in tumor-front was higher than expression in tumor-backside (I-group). RANK-expression in the tumor-front and the tumor-center was higher than expression in tumor-backside in all groups. qPCR showed a 20-43x higher RANKL-mRNA expression in 3/5 tumor organoid samples compared to a normal squamous cell organoid line and no higher mRNA-expression of OPG and RANK. There was no correlation between protein and mRNA expression in the HNSCC organoids. Conclusion The number of osteoclasts and their regulating proteins RANKL/OPG/RANK differ between OSCC patients with and without bone invasion. Bone invasive OSCCs have more osteoclasts and express more RANKL in tumor-front, which suggest that OSCC’s induce bone invasion by stimulating osteoclast activation by regulating the production of RANKL/OPG/RANK proteins.