Besides classic tobacco and alcohol risk factors, human papillomavirus (HPV) plays a role in the development of a subset of head and neck squamous cell carcinomas (HNSCCs), and notably oropharynx squamous cell carcinomas (OPSCCs). HPV-induced OPSCCs have a different biological behavior and a better prognosis compared to non-HPV-induced OPSCCs and the eighth-edition TNM classification now separates these two entities. Therefore, determining the HPV status of patients with OPSCC is now essential for treatment, prognosis, and development of clinical trials. In this review, after reminding essential steps of HPV implication in the cell cycle, we describe the existing tools that are currently feasible in routine practice according to facilities available in health structures, with their benefits and drawbacks: HPV PCR, E6/E7 mRNA RT-PCR, E6/E7 mRNA in situ hybridization, HPV DNA in situ hybridization, and P16 immunochemistry. Besides these traditional HPV detection tools, novel diagnostic approaches are being evaluated for HPV-induced OPSCC "ultrastaging." E6 humoral response and ddPCR-detecting HPVct DNA are two techniques performed on blood and are therefore non-invasive. Baseline E6 humoral levels could have a prognostic value, and HPVct DNA could be helpful for HPV OPSCC recurrence monitoring. At last, next-generation sequencing (NGS)-based "capture HPV" is a technique feasible on biopsies and circulating DNA material. It helps characterize HPV integration status and sites, and it could define prognostic subgroups in HPV-induced OPSCC. These novel precision detection tools could be further integrated in the care of patients with HPV-induced OPSCC.
Five to 10% of desmoid-type fibromatosis (DF) arise in the context of familial adenomatous polyposis (FAP). The beta-catenin gene (CTNNB1) exon 3 mutations are found in 90% of DF (except those associated with FAP) in two codonscodon 41 (p.T41A) and codon 45 (p.S45F and p.S45P) which are serine and threonine phosphorylation sites required for beta-catenin degradation. Mutations p.S45F are associated with a higher risk of recurrence. Among 64 patients with DF and documented CTNNB1 mutational status treated with oral weekly vinorelbine for 6 months, p.S45F or p.S45P mutations were associated with longer time to treatment failure compared to p.T41A or wild type tumors (HR : 2.78, 95%CI: 1.23-6.27), p = 0.04. The functional impact of codons 41 and 45 mutations is certainly different, since the phosphorylation of amino acid 45 targeted by casein kinase-1 serves as a priming phosphorylation for GSK-3β targeting the amino acid 41. Research.
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