International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY).Methods PurposeControversies exist in regard to surgical neck management in total laryngectomies (TL). Thus, in this review, we try to summarize the current opinions about variant genetic changes and multiple immune alterations induced by different oral cancer carcinogens and discuss the prospects of targeted immunotherapeutic strategies based on specific immune abnormalities caused by different carcinogens, as a predictive way to improve clinical outcomes of immunotherapy-treated oral cancer patients. On the other hand, immune heterogeneity of cancer patients is a huge obstacle for enhancing the clinical efficacy of tumor immunotherapy. However, more and more attention has been attracted to the influence of carcinogens on the local immune status. This phenomenon was partly explained by the genetic abnormalities traditionally induced by carcinogens. Coincidentally, initiation and development of oral cancer are attributed to many external factors, such as smoking and drinking, to a great extent. The oral cavity serves as an open local organ of the human body, exposed to multiple external factors from the outside environment. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal–epithelial transition, and structural integrity networks. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients.
To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. The Union for International Cancer Control (UICC) staging system mainly considers clinical factors such as tumor size, nodal status and distant metastasis for estimating prognosis, though only the HPV status was recently considered as a relevant biomarker in the new 8th edition of the UICC staging system (Beltz et al. Currently, the main prognostic parameters of HNSCC are the location and size of the tumor, the presence of distant metastasis and cervical lymph node metastases, which is not sufficient to evaluate the disease outcome (Ernst et al.
2012b), including potential nanomedicines Westmeier et al. 2020 Rothenberg and Ellisen 2012 Stauber et al. Survival rates for HNSCC have not improved significantly, mainly due to the late disease presentation of the patient, lack of suitable biomarkers and their mechanistic understanding, as well as corresponding drugs for (individually) targeted therapy approaches (Campbell et al.