Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous Cell Carcinoma Samples

Carvalho, Ana Carolina de; Melendez, Matias Eliseo; Sabato, Cristina da Silva; Palmero, Edenir Inêz; Arantes, Lídia Maria Rebolho Batista; Neto, Cristovam Scapulatempo

doi:10.1007/s12253-018-0462-0

Cited by 12 publications

(13 citation statements)

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“…Those differences could be explained due to the different proportion of head and neck sub-sites, the number of samples analyzed, and the ethnicity of the patient population (USA, China, India, Taiwan, Poland, and Italy). Brazilian head and neck cancer patients are more likely to be heavy tobacco and alcohol consumers ( 3 ) than HPV + ( 46 – 48 ), which can explain the mutagenic effect on the mucosal epithelia of the upper aerodigestive tract. At Barretos Cancer Hospital, we use p16-immunohistochemistry (p16-IHC) as a surrogate marker for HPV infection, as recommended by the 8th edition of AJCC TNM staging system specifically for oropharyngeal squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

et al. 2020

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Background: Head and neck squamous cell carcinoma (HNSCC) is usually associated to tobacco and alcohol consumption. Increased telomerase activity has been consistently detected in 80-90% of malignant tumors, including HNSCC. Mutations within the promoter region of telomerase reverse transcriptase (TERT) that confer enhanced TERT promoter activity have been reported in two major hotspots, designated C228T and C250T. Objectives: To evaluate TERT promoter mutations C228T and C250T in HNSCC patients from Brazil and correlate with patients' outcome. Materials and Methods: Formalin-fixed paraffin-embedded tissues were obtained from 88 HNSCC patients and analyzed for TERT promoter mutations C228T and C250T by pyrosequencing. Results: The overall prevalence of hotspot TERT mutations in HNSCC samples was of 27.3%, with 6.8% at locus C228T and 20.5% at C250T. The majority (92%) of mutated cases were located in oral cavity, mainly at the tongue. We observed that 94.4% of the patients harboring TERT promoter mutation C250T were alcohol consumers (p = 0.032) and 66.7% of the patients harboring TERT promoter mutation C228T were not alcohol consumers (p = 0.035). The presence of C228T mutation impacted patient outcome, with a significant decrease in disease-free survival (20.0 vs. 63.0%, p =0.017) and in overall survival (16.7 vs. 45.1%, p = 0.017). Conclusion: This is the first report of a TERT promoter mutations in HNSCC patients from South America. The high prevalence of TERT mutation, as well as its association with poor disease-free survival and overall survival, particular at C228T locus might serve as a prognostic biomarker in HNSCC to help clinicians in the management of treatment.

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Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

et al. 2020

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“…Our group has previously showed the clinical relevance of DNA methylation for HNC carcinogenesis through quantitative Polymerase Chain Reaction (qPCR) in samples from different sources 14‐17 ; however, this methodology was not sensitive enough to yield consistent results on plasma samples from HNC patients, probably due to the low levels of ctDNA in plasma samples from HNC patients, as demonstrated by Reference 4. Here, we present, for the first time, the use of ddPCR to test for methylation in FFPE and plasma samples from OpSCC patients.…”

Section: Discussionmentioning

confidence: 88%

Feasibility of methylated ctDNA detection in plasma samples of oropharyngeal squamous cell carcinoma patients

et al. 2020

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Background: Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure. Objectives: To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up. Methods: Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation of CCNA1, DAPK, CDH8, and TIMP3 by droplet digital PCR (ddPCR). Results: Seventy-one percent (37/52) of the biopsies showed methylation of at least one of the evaluated genes and tumor CCNA1 methylation was associated with recurrence-free survival. Methylated circulating tumor DNA (meth-ctDNA) was detected in 11/15 (73.3%) plasma samples; conversely, plasma samples from healthy controls were all negative for DNA methylation (area under the curve = 0.867; 95% confidence interval = 0.720-1.000). Additionally, preliminary results on the detection of meth-ctDNA in plasma collected during follow-up closely matched patient outcome.

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“…Accordingly, it is well established that tobacco/alcohol-associated carcinogenesis is correlated to p53 mutations whereas in HPV-driven HNSCCs in the majority of cases, wild-type (wt) p53 can be detected [ 47 ]. Therefore, in smoking HNSCC patients, which seem to be more common in Germany than in the USA (see Section 4 ), for instance, it might be helpful to distinguish via p53 analysis between tumors that rather are HPV-driven (wt-p53) or indeed associated with tobacco-associated carcinogenesis (mutant p53) [ 48 , 49 ]. Hence, and to overcome the aforementioned problem correlated to p16 INK4A IHC for HPV detection as described in 3.1, Benzerdjeb and colleagues [ 47 ] conducted a study on 110 OPSCC combining p16 INK4A IHC and p53 analysis in terms of detection of wt-p53 versus mutant p53.…”

Section: Detection Methodsmentioning

confidence: 99%

Relevance of Human Papillomaviruses in Head and Neck Cancer—What Remains in 2021 from a Clinician’s Point of View?

Hoffmann

Quabius

2021

Viruses

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Human papillomaviruses (HPV) cause a subset of head and neck cancers (HNSCC). HPV16 predominantly signs responsible for approximately 10% of all HNSCC and over 50% of tonsillar [T]SCCs. Prevalence rates depend on several factors, such as the geographical region where patients live, possibly due to different social and sexual habits. Smoking plays an important role, with non-smoking patients being mostly HPV-positive and smokers being mostly HPV-negative. This is of unparalleled clinical relevance, as the outcome of (non-smoking) HPV-positive patients is significantly better, albeit with standard and not with de-escalated therapies. The results of the first prospective de-escalation studies have dampened hopes that similar superior survival can be achieved with de-escalated therapy. In this context, it is important to note that the inclusion of p16INK4A (a surrogate marker for HPV-positivity) in the 8th TMN-classification has only prognostic, not therapeutic, intent. To avoid misclassification, highest precision in determining HPV-status is of utmost importance. Whenever possible, PCR-based methods, still referred to as the "gold standard”, should be used. New diagnostic antibodies represent some hope, e.g., to detect primaries and recurrences early. Prophylactic HPV vaccination should lead to a decline in HPV-driven HNSCC as well. This review discusses the above aspects in detail.

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Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous Cell Carcinoma Samples

Cited by 12 publications

References 61 publications

TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

Feasibility of methylated ctDNA detection in plasma samples of oropharyngeal squamous cell carcinoma patients

Relevance of Human Papillomaviruses in Head and Neck Cancer—What Remains in 2021 from a Clinician’s Point of View?

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