RESUMEN
BACKGROUND: Herein, we evaluated the attributable fraction (AF) of human papillomavirus (HPV)-mediated (HPV+) oropharyngeal carcinomas (OPCs) in Greece over a recent calendar period. PATIENTS AND METHODS: ORPHEAS, a retrospective, observational, multicenter, cross-sectional study with prospective recruitment, included adult patients with OPC in 2017-2022, each of them with a high-quality, treatment-naïve tumor specimen. The primary endpoint was the HPV-AF, defined as combined positivity for p16INK4a (p16) overexpression and HPV DNA presence by central laboratory testing, among included patients. Other endpoints evaluated the HPV+/HPV- patient/disease characteristics at OPC diagnosis and the HPV subtypes for HPV+ patients. RESULTS: 144/147 patients with available HPV status by central laboratory testing were analyzed [median age: 60.0 years; males: 111 (77.1%)]. The most common tumor anatomical sites were the tonsils (70/147, 48.6%) and the base of the tongue (51, 35.4%), and most patients were at the American Joint Committee on Cancer eighth edition TNM (tumor-node-metastasis) stages III (25, 22.7%) and IV (43, 39.1%). The HPV-AF was 52.1% (75/144; 95% confidence interval 43.6% to 60.5%). Most HPV+ patients were infected by an HPV type targeted by the 9-valent HPV vaccine (72/75, 96.0%), especially HPV16 (70/75, 93.3%). HPV+ compared with HPV- patients were younger (median age 58.0 versus 64.0 years; P = 0.003); more likely to have tumors in the tonsils (65.0% versus 30.4%; P < 0.001); less likely to have tumors in the base of the tongue (25.3% versus 46.4%; P = 0.008); and less frequently at TNM stage IV (20.4% versus 57.1%; overall P < 0.001). CONCLUSIONS: In Greece, we observed a high HPV-AF (52.1%) in OPC, approximating the AFs reported for some Northern European countries. HPV+ versus HPV- patients were younger, more frequently with tonsillar tumors, and less frequently at TNM stage IV. Since most patients were infected by ≥1 HPV type targeted by the 9-valent vaccine, the HPV+ OPC burden could be mitigated through a routine HPV gender-neutral vaccination program.
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BACKGROUND: The purpose of this study was to evaluate the expression of MMP-12 in patients with chronic rhinosinusitis with polyps (CRSwNP). METHODOLOGY: Tissue samples from 37 patients with CRSwNP undergoing functional endoscopic sinus surgery and healthy mucosa specimens from 12 healthy controls were obtained intraoperatively. The mRNA and protein expression levels of MMP-12 were quantified by real-time polymerase chain reaction and Western blotting, respectively. RESULTS: mRNA levels of MMP-12 were significantly elevated in the CRSwNP tissue samples compared to those in control ones. The protein levels of MMP-12 showed a trend of increasing but with no statistical significance. CONCLUSIONS: Elevation of MMP-12 in patients with CRSwNP suggests its potential implication in the pathogenesis of the disease. The difference in the expression profile observed between mRNA and protein levels could be due to post-translational gene expression regulation. Our findings provide evidence that MMP-12 along with other MMPs may serve as a biomarker and therapeutic target in the management of the disease.
Asunto(s)
Pólipos Nasales , Rinitis , Enfermedad Crónica , Humanos , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasales/cirugía , Rinitis/patologíaRESUMEN
BACKGROUND: The expression of metalloproteinases (MMPs) in chronic rhinosinusitis with nasal polyposis (CRSwNP) was reviewed in order to investigate their possible use as therapeutical targets and/or biomarkers. METHODOLOGY: The differences between CRSwNP and normal controls or CRS without NP, as well as the effects of various treatments on MMPs, tissue inhibitors of MMPs (TIMPs) and MMP/TIMP ratios were considered as primary outcomes. Additional factors reported to affect MMP expression levels were noted as secondary outcomes. Data regarding inflammatory subtypes, patientsâ™ clinical characteristics, controls, laboratory method(s) and origin of samples were also pooled. Studies on 10 or fewer patients or on specimens other than nasal and serum were excluded. RESULTS: Forty-three studies were included. Tissue sample origin, allergic rhinitis, smoking, infection, medication intake and primary or recurrent disease should be considered as confounding factors for MMP levels. MMP-1 and -7 were consistently found to be significantly higher in CRSwNP patients than controls. CRSwNP endotypes with distinctly different inflammation patterns seem to present similar MMP-related remodelling patterns. CONCLUSIONS: The existing literature has revealed several population and methodology related confounding factors and remains inconclusive regarding the roles of MMPs in CRSwNP pathophysiology and their possible clinical usefulness as biomarkers and therapeutical targets.