Project description:Sinonasal papilloma is the most common type of sinonasal tumor, with the inverted variant being the most frequent subtype. This variant is known for its potential for recurrence and propensity for malignant transformation. The aim of this study is to investigate the biomarkers and regulatory pathways involved in the development of sinonasal inverted papilloma (SNIP).
Project description:To explore the expression profile, potential functions, and diagnostic and clinicopathological significance of lncRNAs in sinonasal inverted papilloma (SNIP).The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods.
Project description:OBJECTIVE: Although the malignant transformation of sinonasal inverted papilloma (SNIP) into squamous cell carcinomas (SCC) has been reported in the literature, the molecular mechanisms driving this transformation have not been elucidated. This study compares genome-wide DNA methylation between SNIP and SCC arising in SNIP and further validates the expression of aberrantly methylated genes. Methots:We used a comprehensive methylation profiling technique to investigate DNA methylation in CpG islands and promoters in six SNIP samples and seven SCC arising in SNIP samples. A total of 11,201 nominally differentially methylated sites were observed, between SNIP and SCC arising in SNIP. This study is the first to compare the differences in global DNA methylation between SNIP and SCC arising in SNIP.
Project description:Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.
Project description:Inverted sinonasal papilloma (ISP) is a locally aggressive neoplasm associated with sinonasal squamous cell carcinoma (SNSCC) in 10% to 25% of cases. To date, no recurrent mutations have been identified in ISP or SNSCC. Using targeted next-generation sequencing and Sanger sequencing, we identified activating EGFR mutations in 88% of ISP and 77% of ISP-associated SNSCC. Identical EGFR genotypes were found in matched pairs of ISP and associated SNSCC, providing the first genetic evidence of a biologic link between these tumors. EGFR mutations were not identified in exophytic or oncocytic papillomas or non-ISP-associated SNSCC, suggesting that the ISP/SNSCC spectrum is biologically distinct among sinonasal squamous tumors. Patients with ISP harboring EGFR mutations also exhibited an increased progression-free survival compared with those with wild-type EGFR. Finally, treatment of ISP-associated carcinoma cells with irreversible EGFR inhibitors resulted in inactivation of EGFR signaling and growth inhibition. These findings implicate a prominent role for activating EGFR mutations in the pathogenesis of ISP and associated SNSCC and rationalize consideration of irreversible EGFR inhibitors in the therapy of these tumors.
Project description:Objective We review our institution's experience with the treatment of inverted papilloma (IP) with emphasis on the implications of surgical margins for disease control. Design Retrospective chart review of patients with IP treated at the University of Michigan from 1996 to 2011. Setting Tertiary care center. Participants Patients undergoing surgical resection with curative intent for IP. Main Outcome Measures Overall survival, disease-specific survival, and locoregional control were used as main outcome measures. Results We studied 129 patients including 19 with carcinoma arising from IP. Disease-free rates at 2, 3, and 5 years were 79.7%, 77.9%, and 61%, respectively. Overall, 10 of 18 recurrences were detected > 2 years from follow-up, with recurrences detected up to 8 years from surgery. For benign disease, obtaining tissue margins outside of the primary specimen for margin control did not affect disease control rates. Conclusion IP is a disease that requires significant follow-up periods beyond 2 years. For IP without carcinogenesis, acquiring margins outside of the tumor specimen did not appear to affect disease control rates in this study. No clear predictors of malignancy were seen in this study, which highlights the need for further research to predict this phenomenon.
Project description:PurposeAccurate preoperative prediction of the malignant transformation of sinonasal inverted papilloma (IP) is essential for guiding biopsy, planning appropriate surgery and prognosis of patients. We aimed to investigate the value of MRI-based radiomics in discriminating IP from IP-transformed squamous cell carcinomas (IP-SCC).MethodsA total of 236 patients with IP-SCC (n=92) or IP (n=144) were enrolled and divided into a training cohort and a testing cohort. Preoperative MR images including T1-weighted, T2-weighted, and contrast enhanced T1-weighted images were collected. Radiomic features were extracted from MR images and key features were merged into a radiomic model. A morphological features model was developed based on MR morphological features assessed by radiologists. A combined model combining radiomic features and morphological features was generated using multivariable logistic regression. For comparison, two head and neck radiologists were independently invited to distinguish IP-SCC from IP. The area under the receiver operating characteristics curve (AUC) was used to assess the performance of all models.ResultsA total of 3948 radiomic features were extracted from three MR sequences. After feature selection, we saved 15 key features for modeling. The AUC, sensitivity, specificity, and accuracy on the testing cohort of the combined model based on radiomic and morphological features were respectively 0.962, 0.828, 0.94, and 0.899. The diagnostic ability of the combined model outperformed the morphological features model and also outperformed the two head and neck radiologists.ConclusionsA combined model based on MR radiomic and morphological features could serve as a potential tool to accurately predict IP-SCC, which might improve patient counseling and make more precise treatment planning.
Project description:ImportanceThe risk factors for the recurrence of sinonasal inverted papilloma are still unclear.ObjectiveTo investigate the potential association between the Krouse classification and the recurrence rates of sinonasal inverted papilloma.Data sourcesThe EMBASE and MEDLINE databases were searched for the period January 1, 1964, through September 30, 2016, using the following search strategy: (paranasal sinuses [Medical Subject Headings (MeSH) terms] OR sinonasal [all fields]) AND (inverted papilloma [MeSH terms] OR (inverted [all fields] AND papilloma [all fields]).Study selectionThe inclusion criteria were (1) studies including sinonasal inverted papilloma only and no other forms of papillomas, such as oncocytic papilloma; (2) minimum follow-up of 1 year after the surgery; and (3) clear report of cases (recurrence) and controls according to the Krouse classification system or deducible from the full-text article. Literature search was performed by 2 reviewers. Of the 625 articles retrieved in the literature, 97 full-text articles were reviewed. Observational cohort studies or randomized controlled trials were included, and the following variables were extracted from full-text articles: authors of the study, publication year, follow-up data, and number of cases (recurrence) and controls (no recurrence) in each of the 4 stages of the Krouse classification system.Data extraction and synthesisThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Odds ratios (ORs) and 95% CIs were estimated, and data of included studies were pooled using a random-effects model.Main outcomes and measuresThe main outcome was recurrence after surgical removal of sinonasal inverted papilloma according to each stage of the Krouse classification system.ResultsThirteen studies comprising 1787 patients were analyzed. A significant increased risk of recurrence (51%) was highlighted for Krouse stage T3 disease when compared with stage T2 (pooled OR, 1.51; 95% CI, 1.09-2.09). No significant difference in risk of recurrence was found between Krouse stages T1 and T2 disease (pooled OR, 1.14; 95% CI, 0.63-2.04) or between stages T3 and T4 (pooled OR, 1.27; 95% CI, 0.72-2.26).Conclusions and relevanceInverted papillomas classified as stage T3 according to the Krouse classification system presented a 51% higher likelihood of recurrence. Head and neck surgeons must be aware of this higher likelihood of recurrence when planning and performing surgery for sinonasal inverted papilloma.