Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification.

Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV OPSCC patients.

Evaluation of an open-source machine-learning tool to quantify bone marrow plasma cells.

Aims: The objective of this study was to develop and validate an open-source digital pathology tool, QuPath, to automatically quantify CD138-positive bone marrow plasma cells (BMPCs).

Methods: We analysed CD138-scanned slides in QuPath. In the initial training phase, manual positive and negative cell counts were performed in representative areas of 10 bone marrow biopsies.

Does HPV Subtype Predict Outcomes in Head and Neck Cancers?

Background: Recently, reanalysis of The Cancer Genome Atlas study demonstrated that human papillomavirus (HPV) genotypes in head and neck cancers other than HPV-16 have inferior survival to HPV-16-positive tumors. We aimed to examine the association of HPV subtypes and survival in a large cohort of patient samples from our institution.

Methods: Fresh frozen primary site biopsy samples were collected either in clinic or at the time of surgery.

Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis.

Background: Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration.

TAM family receptors in conjunction with MAPK signalling are involved in acquired resistance to PI3Kα inhibition in head and neck squamous cell carcinoma.

Background: Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs).

Genomic and human papillomavirus profiling of an oral cancer cohort identifies TP53 as a predictor of overall survival.

Background: The genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project. We attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort.

Methods: Patient demographic data along with data from final pathology was collected.

Splenic Angiosarcoma with Bone Marrow Involvement Initially Diagnosed as Systemic Mastocytosis: A Case Report.

We describe the case of a 67-year-old female patient presenting with constitutional symptoms and rapid decline. Two bone marrow core biopsies were performed, with spindled cells identified and thought to represent marrow involvement by systemic mastocytosis on the first biopsy. A diagnosis of metastatic vascular malignancy with sarcomatoid features was favored on the second core biopsy.

Disruption of the RICTOR/mTORC2 complex enhances the response of head and neck squamous cell carcinoma cells to PI3K inhibition.

Phosphoinositide 3-kinase (PI3K) is aberrantly activated in head and neck squamous cell carcinomas (HNSCC) and plays a pivotal role in tumorigenesis by driving Akt signaling, leading to cell survival and proliferation. Phosphorylation of Akt Thr308 by PI3K-PDK1 and Akt Ser473 by mammalian target of rapamycin complex 2 (mTORC2) activates Akt. Targeted inhibition of PI3K is a major area of preclinical and clinical investigation as it reduces Akt Thr308 phosphorylation, suppressing downstream mTORC1 activity.

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed.

Isolated traumatic rupture of the gallbladder.

Gallbladder injury resulting from blunt abdominal trauma is rare, being found in only about 2% of patients who undergo laparotomy for abdominal trauma. Its small size and anatomic location-partially embedded in the liver tissue, surrounded by the omentum and intestines, and overlaid by the rib cage-provides good protection. Diagnosis can be difficult, and delay may result in the development of weight loss, nausea, vomiting, abdominal distension, jaundice, ascites, and abdominal pains.