scholarly journals Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study)

2021 ◽  
Author(s):  
Marc Oliva ◽  
Pierre H. H. Schneeberger ◽  
Victor Rey ◽  
Matthew Cho ◽  
Rachel Taylor ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Taxonomic Composition ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Oral Microbiome ◽  
Metagenomic Sequencing ◽  
Α Diversity ◽  
16S Rna ◽  
The Impact

Abstract Background Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT). Methods Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity. Results A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use. Conclusions Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.

Prognostic Impact of High-Risk Pathologic Features in HPV-Related Oropharyngeal Squamous Cell Carcinoma and Tobacco Use

2018 ◽  
Vol 160 (5) ◽  
pp. 855-861 ◽  
Author(s):  
Anvesh R. Kompelli ◽  
Patrick Morgan ◽  
Hong Li ◽  
William Harris ◽  
Terry A. Day ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tobacco Use ◽  
Squamous Cell ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Prognostic Impact ◽  
Pathologic Features ◽  
Eighth Edition ◽  
The Impact ◽  
Heavy Smokers

Objectives To assess the impact of pathologic features and chronic tobacco use on human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC). Study Design Case series with chart review. Setting Single tertiary care referral center. Subject and Methods A total of 301 patients were treated for OPSCC from 2008 to 2016. Clinical and pathologic T and N stage, American Joint Committee on Cancer (AJCC) stage (seventh and eighth edition staging manuals), cigarette pack years, alcohol use, and presence of extranodal extension (ENE), perineural invasion (PNI), or lymphovascular invasion (LVI) were assessed. Patients were stratified into HPV negative, HPV-positive heavy smokers (≥20 pack years), and HPV-positive nonsmokers. Five-year survival by Kaplan-Meier method was assessed. Results Of the HPV-positive patients, 97 were nonsmokers and 73 were heavy smokers. HPV-positive heavy smokers had significantly decreased survival compared to their nonsmoking counterparts ( P = .02). The presence of ENE was associated with a significantly decreased 5-year survival ( P = .02) in heavy smokers relative to nonsmokers in HPV-positive patients. Furthermore, for the AJCC eighth edition, clinically stage 1 HPV-positive heavy smokers had significantly decreased survival relative to nonsmokers ( P = .01). Conclusions This series highlights the potential need for more aggressive therapy for HPV-positive patients with extensive tobacco use under the new staging system.

scholarly journals Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Manolito G. Torralba ◽  
Gajender Aleti ◽  
Weizhong Li ◽  
Kelvin Jens Moncera ◽  
Yi-Han Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Virulence Factors ◽  
Squamous Cell ◽  
Tumor Tissue ◽  
Oral Microbiome ◽  
Metagenomic Sequencing ◽  
Factors Associated

AbstractThe human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.

scholarly journals Differential Activation of ERK Signaling in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 584 ◽  
Author(s):  
Chao Rong ◽  
Marie Muller ◽  
Christa Flechtenmacher ◽  
Dana Holzinger ◽  
Gerhard Dyckhoff ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Outcome ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Erk Signaling ◽  
Primary Tumors ◽  
The Impact

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) forms a distinct tumor entity with better survival clinical outcome. Numerous underlying molecular mechanisms have been postulated for differences in treatment response, but the impact of MEK/ERK signaling, a main driver of carcinogenesis in various cancers including OPSCC and key player mediating therapy resistance remains elusive. In a retrospective experimental cohort study, primary tumor samples from OPSCC patients (n = 124) were available on tissue microarrays (TMAs) and expression levels of phosphorylated ERK1/2 (pERK1/2) were detected by immunohistochemical staining. Correlations of pERK1/2 expression patterns with clinicopathological features and clinical outcome were evaluated by statistical analysis. A low pERK1/2 expression was strongly associated with HPV-related OPSCC, while primary tumors with high pERK1/2 staining showed a distinctly worse survival outcome and were associated with higher cellular differentiation. Co-activation of both ERK1/2 and AKT was a common event and was associated with unfavorable prognosis in our cohort. However, the combinatorial analysis of pAKT (Ser473) and pERK1/2 did not strengthen the predictive power of pERK1/2, suggesting that pERK1/2 plays a more significant function in OPSCC. In summary, our data provide a compelling experimental and statistical evidence that low levels of tumor cell intrinsic ERK1/2 activation contribute at least in part to the favorable outcome of HPV-related OPSCC. On the other hand, presented findings indicate that non-HPV-related OPSCC with elevated ERK phosphorylation are at high risk for treatment failure and might benefit from targeted therapy of MEK/ERK signaling.

scholarly journals Analysis of Salivary Mycobiome in a Cohort of Oral Squamous Cell Carcinoma Patients From Sudan Identifies Higher Salivary Carriage of Malassezia as an Independent and Favorable Predictor of Overall Survival

2021 ◽  
Vol 11 ◽  
Author(s):  
Nazar Mohamed ◽  
Jorunn Litlekalsøy ◽  
Israa Abdulrahman Ahmed ◽  
Einar Marius Hjellestad Martinsen ◽  
Jessica Furriol ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Oral Microbiome ◽  
Its2 Region ◽  
Kaplan Meier ◽  
Compositional Patterns ◽  
The Impact

BackgroundMicrobial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the “rare biosphere” of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS).Materials and MethodsUnstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic–mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan–Meier and Cox regression survival analyses (SPPS).ResultsSixteen genera were identified exclusively in the saliva of OSCC patients. Candida, Malassezia, Saccharomyces, Aspergillus, and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan–Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16–0.93, p = 0.03).ConclusionThe fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC.

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