Unraveling most abundant mutational signatures in head and neck cancer.

Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO-HNC (Heidelberg Center for Personalized Oncology-head and neck cancer) (n = 83) and TCGA-HNSC (The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma) (n = 506) cohorts revealed five common mutational signatures (Catalogue of Somatic Mutations in Cancer [COSMIC] Signatures 1, 2, 3, 13 and 16) and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16). Unsupervised hierarchical clustering identified four clusters (A, B, C1 and C2) of which Subcluster C2 was enriched for cases with a higher frequency of signature 16 mutations. Tumors of Subcluster C2 had significantly lower p16INK4A expression accompanied by homozygous CDKN2A deletion in almost one half of cases. Survival analysis revealed an unfavorable prognosis for patients with tumors characterized by a higher mutation burden attributed to signature 16 as well as cases in Subcluster C2. Finally, a LASSO-Cox regression model was applied to prioritize clinically relevant signatures and to establish a prognostic risk score for head and neck squamous cell carcinoma patients. In conclusion, our study provides a proof of concept that computational analysis of somatic mutational signatures is not only a powerful tool to decipher environmental and intrinsic processes in the pathogenesis of HNC, but could also pave the way to establish reliable prognostic patterns.

Ceramic anterior veneer restorations in periodontally compromised patients: A retrospective study.

BACKGROUND: Successful periodontal therapy can lead to poor esthetic results, especially in the anterior region, for which there are treatment options such as direct composite or indirect veneer restorations. Until now, there are no data describing the long-term results of veneer restorations in periodontally treated patients. The aim of this retrospective study was to evaluate the outcome of anterior porcelain veneer restorations in periodontally compromised and noncompromised patients. METHODS: Periodontally healthy and periodontally compromised patients, who had received anterior veneer restorations at least 5 years ago, were invited to a follow-up examination. Groups were divided according to their periodontal diagnosis (periodontally healthy, stage I/II, stage III/IV). Tooth loss, veneer loss, biologic parameters, and complication rates were examined. Also, veneers were evaluated according to modified United States Public Health Service criteria. RESULTS: A total of 68 patients with 312 veneers were examined with a mean follow-up time of 8 years. Veneered teeth in patients with periodontitis stage III/IV showed no difference regarding tooth-specific, overall, and functional veneer survival when compared to periodontally healthy patients (Kaplan-Meier analyses). In Cox regression analysis, follow-up time had an impact on complications and veneer loss, whereas periodontal diagnosis showed no significant influence on the survival of restorations. Comparative tests showed that patients with severe periodontitis at baseline have slightly lower veneer survival rates after 8 years and slightly higher complication rates after 13 years. CONCLUSION: Long-term results and complication rates of veneer restorations in periodontally compromised patients are comparable to periodontally healthy patients over a mean follow-up of 8 years.