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“Background: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach.
Methods: Twenty HPV+ and 20 HPV-laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry
were used selleck to further validate findings.
Results: HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification
occurs in the majority of HPV- tumors.
Conclusion: These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR Ferroptosis inhibitor inhibitors in HNSCC.”
“OBJECTIVES: While neoadjuvant chemoradiation followed by surgery has been shown to improve the survival of patients with locally advanced oesophageal cancer, it is not known whether neoadjuvant chemoradiation has a beneficial or harmful effect on the non-responders. We aimed to compare the outcomes among neoadjuvant chemoradiation responders, non-responders and patients receiving primary oesophagectomies for resectable locally advanced oesophageal squamous cell carcinoma.
METHODS: Eighty-four non-T1-2N0 oesophageal squamous cell carcinoma patients were included. Thirty-eight patients received primary resection and 46 patients received SNX-5422 supplier neoadjuvant
chemoradiation. The overall survival of chemoradiation responders (< 50% residual tumour), non-responders (> 50% residual tumour and those who shifted to definitive chemoradiation instead of surgery due to tumour progression) and patients receiving primary resection were compared. Clinical parameters were also compared between responders and non-responders.
RESULTS: There was no overall difference in survival between neoadjuvant chemoradiation and primary resection groups (2-year overall survival rates: 45.6 vs 54.3%, P = 0.442). In patients receiving neoadjuvant chemoradiation followed by surgery, pathological responders had significantly higher 2-year overall survival rates than non-responders (64.5 vs 38.9%, P = 0.043).