Background: Somatic TP53 mutations are frequent in head and neck squamous cell carcinoma (HNSCC) and are important pathogenic factors. Objective: To study TP53 mutations relative to the presence of human papillomavirus (HPV) in tumors in HNSCC patients. Methods: Using a custom-made next-generation sequencing (NGS) panel on formalin-fixed, paraffin-embedded tumor tissue, we analyzed somatic TP53 mutations and the TP53 single-nucleotide polymorphism (SNP) codon 72 (P72R; rs1042522) (proline → arginine) from 104 patients with HNSCC. Results: Only 2 of 44 patients with HPV-positive (HPV(+)) HNSCC had a TP53 somatic mutation, as opposed to 42/60 HPV-negative (HPV(−)) HNSCC patients (p < 0.001). Forty-five different TP53 somatic mutations were detected. Furthermore, in HPV(−) patients, we determined an 80% prevalence of somatic TP53 mutations in the TP53 R72 polymorphism cohort versus 40% in the TP53 P72 cohort (p = 0.001). A higher percentage of patients with oral cavity SCC had TP53 mutations than HPV(−) oropharyngeal (OP) SCC patients (p = 0.012). Furthermore, 39/44 HPV(+) tumor patients harbored the TP53 R72 polymorphism in contrast to 42/60 patients in the HPV(−) group (p = 0.024). Conclusions: Our observations show that TP53 R72 polymorphism is associated with a tumor being HPV(+). We also report a higher percentage of somatic TP53 mutations with R72 than P72 in HPV(−) HNSCC patients.

Background: Norepinephrine is commonly used during acute burn resuscitation to maintain adequate perfusion pressure. However, its effects, together with the burn-induced catecholamine surge, on arterial α₁-adrenergic receptors (α₁-AR) remain unclear. This study examined whether burn injury and continuous norepinephrine infusion alter arterial α₁-AR subtype expression at the transcriptional and protein levels. Methods: Sprague–Dawley rats were randomized to full-thickness scald burn involving 25% total body surface area with continuous intravenous norepinephrine or sodium chloride (NaCl) infusion, sham injury with norepinephrine infusion, or untreated controls. Mean arterial pressure (MAP) was measured at baseline and before euthanasia (six or 24 h). Aorta, carotid, and renal arteries were collected for analysis of α₁-AR subtypes (Adra1a, Adra1b, and Adra1d) using quantitative PCR (qPCR) and immunohistochemistry (IHC). Results: Norepinephrine efficiently increased MAP in sham animals. In burned animals with norepinephrine, MAP increased at six hours (+10.6 mmHg) but fell below baseline at 24 h (−6.4 mmHg). Burned animals given NaCl had persistently lower MAP than those given norepinephrine, at six hours (−19.1 mmHg) and 24 h (−21.1 mmHg). qPCR demonstrated significant downregulation of Adra1b in the renal artery across all groups compared to control (7.8–16.4-fold, p < 0.001). Overall, changes in protein expression across different vascular beds and receptor subtypes were inconsistent. Conclusions: Norepinephrine increased MAP in both sham and burned animals, confirming the drug’s efficacy. Burn injury and sustained norepinephrine exposure were associated with early, vessel-specific alterations in α₁-AR mRNA expression. The absence of consistent protein-level changes within 24 h suggests a delay in receptor expression on protein level.