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Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

ABSTRACT: To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions.Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglottic carcinoma specimens using in situ hybridization. Survival analysis was performed by Kaplan-Meier analysis, factors were compared using log-rank test, and prognostic factors were determined using Cox proportional hazards model. The relationship between subregions and clinicopathologic factors was analyzed using Chi-square tests.HPV prevalence differed between patients with aryepiglottic fold carcinoma and ventricle carcinoma (P < .05). The local-regional control rates, overall survival rates or cancer specific survival rates were significantly different between different subregions. Univariate analysis indicated that pTNM classification, pN spread, and subregion were associated with prognosis (P < .05). Multivariate analysis indicated that pTNM classification and subregion were associated with supraglottic carcinoma prognosis. The survival rate was better for patients with carcinoma of the epiglottis or ventricular bands compared to those with carcinoma in the aryepiglottic fold or ventricle (P = .012).Subregion may be a new prognostic factor for supraglottic squamous cell carcinoma. Different supraglottic carcinoma subregions have distinct clinical features such as HPV expression, lymph node metastasis rate, local-regional control and prognosis. Therefore, it is necessary to subdivide supraglottic squamous cell carcinomas into several subregion groups to individualize therapy.

SUBMITTER: Ding W

PROVIDER: S-EPMC5695779 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

Ding Weiquan W Liu Tianrun T Liang Jiangang J Hu Tingbao T Cui Shaoyun S Zou Guorong G Cai Weiwei W Yang Ankui A

PloS one 20171120 11

<h4>Objective</h4>To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions.<h4>Methods</h4>Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglo ...[more]

PMID: 29155864

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Project description:Mutations in the tumor suppressor CYLD, known to be causative of cylindromas, were recently described in a subset of high-risk (hr) HPV-positive head and neck squamous cell carcinomas (HNSCC). Pathologic and genetic characterization of these CYLD-mutant carcinomas, however, remains limited. Here, we investigated whether CYLD mutations characterize a histopathologically and genomically distinct subset of hrHPV-positive HNSCC. Comprehensive genomic profiling via hybrid capture-based DNA sequencing was performed on 703 consecutive head and neck carcinomas with hrHPV sequences, identifying 148 unique cases (21%) harboring CYLD mutations. Clinical data, pathology reports, and histopathology were reviewed. CYLD mutations included homozygous deletions (n = 61/148; 41%), truncations (n = 52; 35%), missense (n = 26; 18%) and splice-site (n = 9; 6%) mutations, and in-frame deletion (n = 1; 1%). Among hrHPV-positive HNSCC, the CYLD-mutant cohort showed substantially lower tumor mutational burden than CYLD-wildtype cases (n = 555) (median 2.6 vs. 4.4 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (11% vs. 34%, p < 0.0001), KMT2D (1% vs. 16%, p < 0.0001), and FBXW7 (3% vs. 11%, p = 0.0018). Male predominance (94% vs. 87%), median age (58 vs. 60 years), and detection of HPV16 (95% vs. 89%) were similar. On available histopathology, 70% of CYLD-mutant HNSCC (98/141 cases) contained hyalinized material, consistent with basement membrane inclusions, within crowded aggregates of tumor cells. Only 7% of CYLD-wildtype cases demonstrated this distinctive pattern (p < 0.0001). Histopathologic patterns of CYLD-mutant HNSCC lacking basement membrane inclusions included nonkeratinizing (n = 22, 16%), predominantly nonkeratinizing (nonkeratinizing SCC with focal maturation; n = 10, 7%), and keratinizing (n = 11, 8%) patterns. The latter two groups showed significantly higher frequency of PTEN alterations compared with other CYLD-mutant cases (38% [8/21] vs. 7% [8/120], p = 0.0004). Within our cohort of hrHPV-positive HNSCCs, CYLD mutations were frequent (21%) and demonstrated distinctive clinical, histopathologic, and genomic features that may inform future study of prognosis and treatment.

Project description:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing. Disease stage and smoking history are often used in current clinical trials to select patients for deintensification therapy, but these features lack sufficient accuracy for predicting disease relapse. Our purpose was to develop an imaging signature to assess early response and predict outcomes of OPSCC. Methods: We retrospectively analyzed 162 OPSCC patients treated with concurrent chemoradiotherapy, equally divided into separate training and validation cohorts with similar clinical characteristics. A robust consensus clustering approach was used to spatially partition the primary tumor and involved lymph nodes into subregions (i.e., habitats) based on 18F-FDG PET and contrast CT imaging. We proposed quantitative image features to characterize the temporal volumetric change of the habitats and peritumoral/nodal tissue between baseline and midtreatment. The reproducibility of these features was evaluated. We developed an imaging signature to predict progression-free survival (PFS) by fitting an L1-regularized Cox regression model. Results: We identified 3 phenotypically distinct intratumoral habitats: metabolically active and heterogeneous, enhancing and heterogeneous, and metabolically inactive and homogeneous. The final Cox model consisted of 4 habitat evolution-based features. In both cohorts, this imaging signature significantly outperformed traditional imaging metrics, including midtreatment metabolic tumor volume for predicting PFS, with a C-index of 0.72 versus 0.67 (training) and 0.66 versus 0.56 (validation). The imaging signature stratified patients into high-risk versus low-risk groups with 2-y PFS rates of 59.1% versus 89.4% (hazard ratio, 4.4; 95% confidence interval, 1.4-13.4 [training]) and 61.4% versus 87.8% (hazard ratio, 4.6; 95% confidence interval, 1.7-12.1 [validation]). The imaging signature remained an independent predictor of PFS in multivariable analysis adjusting for stage, human papillomavirus status, and smoking history. Conclusion: The proposed imaging signature allows more accurate prediction of disease progression and, if prospectively validated, may refine OPSCC patient selection for risk-adaptive therapy.

Project description:BackgroundIn early stage laryngeal squamous cell carcinoma (LSCC) radiotherapy with curative intent is a major treatment modality. TNM classification is used to define patients eligible for radiotherapy. Studies in early stage glottic LSCC identified several predictive biomarkers associated with local control. However, we recently reported that this predictive value could not be confirmed in supraglottic LSCC.ObjectiveTo examine whether clinical behavior and protein expression patterns of these biomarkers differ between glottic and supraglottic LSCC.Study designRetrospective cohort study.MethodsTumor tissue sections of 196 glottic and 80 supraglottic T1-T2 LSCC treated primarily with RT were assessed immunohistochemically for expression of pAKT, Ki-67 and β-Catenin. Expression data of HIF-1α, CA-IX, OPN, FADD, pFADD, Cyclin D1, Cortactin and EGFR in the same cohort of glottic and supraglottic LSCC, were retrieved from previously reported data. The relationship between glottic and supraglottic sublocalization and clinicopathological, follow-up, and immunohistochemical staining characteristics were evaluated using logistic regression and Cox regression analyses.ResultsGlottic LSCC were correlated with male gender (P = .001), hoarseness as a primary symptom (P < .001), T1 tumor stage (P < .001), negative lymph node status (P < .001), and an older age at presentation (P = .004). Supraglottic LSCC patients developed more post-treatment distant metastasis when adjusted for gender, age, and T-status. While supraglottic LSCC was associated with higher expression of HIF-1α (P = .001), Cortactin (P < .001), EGFR (P < .001), and Ki-67 (P = .027), glottic LSCC demonstrated higher expression of CA-IX (P = .005) and Cyclin D1 (P = .001).ConclusionDifferences in clinicopathological and immunohistochemical staining characteristics suggest that T1-T2 glottic and supraglottic LSCC should be considered as different entities.Level of evidenceN/A. Laryngoscope, 2020.

Project description:PurposeThere is a lack of biomarkers for accurately prognosticating outcome in both human papillomavirus-related (HPV+) and tobacco- and alcohol-related (HPV-) oropharyngeal squamous cell carcinoma (OPSCC). The aims of this study were to i) develop and evaluate radiomic features within (intratumoral) and around tumor (peritumoral) on CT scans to predict HPV status; ii) investigate the prognostic value of the radiomic features for both HPV- and HPV+ patients, including within individual AJCC eighth edition-defined stage groups; and iii) develop and evaluate a clinicopathologic imaging nomogram involving radiomic, clinical, and pathologic factors for disease-free survival (DFS) prediction for HPV+ patients.Experimental designThis retrospective study included 582 OPSCC patients, of which 462 were obtained from The Cancer Imaging Archive (TCIA) with available tumor segmentation and 120 were from Cleveland Clinic Foundation (CCF, denoted as SCCF) with HPV+ OPSCC. We subdivided the TCIA cohort into training (ST, 180 patients) and validation (SV, 282 patients) based on an approximately 3:5 ratio for HPV status prediction. The top 15 radiomic features that were associated with HPV status were selected by the minimum redundancy-maximum relevance (MRMR) using ST and evaluated on SV. Using 3 of these 15 top HPV status-associated features, we created radiomic risk scores for both HPV+ (RRSHPV+) and HPV- patients (RRSHPV-) through a Cox regression model to predict DFS. RRSHPV+ was further externally validated on SCCF. Nomograms for the HPV+ population (Mp+RRS) were constructed. Both RRSHPV+ and Mp+RRS were used to prognosticate DFS for the AJCC eighth edition-defined stage I, stage II, and stage III patients separately.ResultsRRSHPV+ was prognostic for DFS for i) the whole HPV+ population [hazard ratio (HR) = 1.97, 95% confidence interval (CI): 1.35-2.88, p < 0.001], ii) the AJCC eighth stage I population (HR = 1.99, 95% CI: 1.04-3.83, p = 0.039), and iii) the AJCC eighth stage II population (HR = 3.61, 95% CI: 1.71-7.62, p < 0.001). HPV+ nomogram Mp+RRS (C-index, 0.59; 95% CI: 0.54-0.65) was also prognostic of DFS (HR = 1.86, 95% CI: 1.27-2.71, p = 0.001).ConclusionCT-based radiomic signatures are associated with both HPV status and DFS in OPSCC patients. With additional validation, the radiomic signature and its corresponding nomogram could potentially be used for identifying HPV+ OPSCC patients who might be candidates for therapy deintensification.

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Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

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Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

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