Oropharyngeal squamous cell carcinoma: Prognostic factors for development of distant metastases and oncological outcomes

Mattioli, Francesco; Manto, Alfredo Lo; Miglio, Matteo; Serafini, Edoardo; Rossi, Davide; Valerini, Sara; Tonelli, Roberto; Fermi, Matteo; Pugliese, Giuseppe; Bertolini, Federica; D’Angelo, Elisa; Depenni, Roberta; Dominici, Massimo; Lohr, Frank; Marchioni, Daniele

doi:10.1002/hed.27354

Cited by 2 publications

(4 citation statements)

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“…Exonuclease V is a DNA-specific exonuclease able to cleave linear single and double-stranded DNA strands into short oligos (<25 bp) ( 35 ). However, circular extrachromosomal episomes is resistant to this exonuclease ( 33 ).…”

Section: Resultsmentioning

confidence: 99%

“…Head and neck surgeons have also been actively involved in identifying better prognostication tools and safer treatment options to treat HPV-positive OPSCCs ( 19 , 20 ). Amidst these efforts, up to 15% of HPV-positive OPSCC patients continue to show resistance to current treatment modalities ( 22 , 35 ). For example, our clinical team at the McGill University Health Centre currently runs the NECTORS clinical trial.…”

Section: Discussionmentioning

confidence: 99%

“…For example, our clinical team at the McGill University Health Centre currently runs the NECTORS clinical trial. This trial combines neoadjuvant systemic treatment and locoregional treatment de-intensification for HPV-positive OPSCC patients to improve both oncologic and patient-reported quality of life outcomes (NCT04277858) ( 35 – 37 ). A fraction of OPSCC patients also continue to be misdiagnosed with HPV-related OPSCC due to the relatively moderate specificity (83%) of p16 INK4A (IHC) as a surrogate marker for HPV positivity ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

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Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration

Gauthier,

Kadam,

Leveque

et al. 2023

Front. Oncol.

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IntroductionIn North America and in most European countries, Human Papillomavirus (HPV) is responsible for over 70% of oropharyngeal squamous cell carcinomas. The burden of OPSCC, in high-income countries, has been steadily increasing over the past 20 years. As a result, in the USA and in the UK, the burden of HPV-related oropharyngeal squamous cell carcinoma in men has now surpassed that of cervical cancer in women. However, the oncogenic impact of high-risk HPV integration in oropharyngeal squamous cell carcinomas hasn’t been extensively studied. The present study aimed to explore the patterns of HPV integration in oropharyngeal squamous cell carcinomas and to assess the feasibility and reliability of long-read sequencing technology in detecting viral integration events in oropharyngeal head and neck cancers.MethodsA cohort of eight HPV-positive OPSCC pre-treatment patient tumors (four males and four females), were selected. All patients received a p16INK4A positive OPSCC diagnosis and were treated at the McGill University Health Centre, a quaternary center in Montreal. A minimum of 20mg of tumor tissue was used for DNA extraction. Extracted DNA was subjected to Nanopore long-read sequencing to detect and analyze for the presence of high-risk HPV sequences. PCR and Sanger sequencing experiments were performed to confirm Nanopore long-read sequencing readings.ResultsNanopore long-read sequencing showed that seven out of eight patient samples displayed either integrated or episomal high-risk HPV sequences. Out of these seven samples, four displayed verifiable integration events upon bioinformatic analysis. Integration confirmation experiments were designed for all four samples using PCR-based methods. Sanger sequencing was also performed. Four distinct HPV integration patterns were identified: concatemer chromosomal integration in a single chromosome, bi-chromosomal concatemer integration, single chromosome complete integration and bi-chromosomal complete integration. HPV concatemer integration also proved more common than full HPV integration events.Conclusion and relevanceLong-read sequencing technologies can be effectively used to assess HPV integration patterns in OPSCC tumors. Clinically, more research should be conducted on the prognostication value of high-risk HPV integration in OPSCC tumors using long-read sequencing technology.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration

Gauthier,

Kadam,

Leveque

et al. 2023

Front. Oncol.

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“…The TNM system is the most widely utilised framework to stage LSCC and provide valuable predictions of survival 2 . The prognostic heterogeneity inherent to laryngeal neoplasms, particularly for those at advanced stages, has been the subject of extensive studies from our group and others aimed at identification of potential predictors [3][4][5][6][7][8][9][10] . Several prognostic factors have been implicated in LSCC, including disease stage, surgical margin status, tumour differentiation, extranodal extension (ENE), and the presence of lympho-vascular (LVI) or perineural invasion (PNI) [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Thyroid cartilage infiltration in advanced laryngeal cancer: prognostic implications and predictive modelling

Montenegro,

Paderno,

Ravanelli

et al. 2024

Acta Otorhinolaryngol Ital

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SUMMARY Objective Detection of laryngeal cartilage invasion is of great importance in staging of laryngeal squamous cell carcinoma (LSCC). The role of prognosticators in locally advanced laryngeal cancer are still widely debated. This study aimed to assess the impact of volume of thyroid cartilage infiltration, as well as other histopathologic variables, on patient survival. Materials and methods We retrospectively analysed 74 patients affected by pT4 LSCC and treated with total laryngectomy between 2005 and 2021 at the Department of Otorhinolaryngology – Head and Neck Surgery of the University of Brescia, Italy. We considered as potential prognosticators histological grade, perineural (PNI) and lympho-vascular invasion (LVI), thyroid cartilage infiltration, and pTN staging. Pre-operative CT or MRI were analysed to quantify the volume of cartilage infiltration using 3D Slicer software. Results The 1-, 3-, and 5-year disease free survivals (DFS) were 76%, 66%, and 64%, respectively. Using machine learning models, we found that the volume of thyroid cartilage infiltration had high correlation with DFS. Patients with a higher volume (>670 mm 3 ) of infiltration had a worse prognosis compared to those with a lower volume. Conclusions Our study confirms the essential role of LVI as prognosticator in advanced LSCC and, more innovatively, highlights the volume of thyroid cartilage infiltration as another promising prognostic factor.

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Oropharyngeal squamous cell carcinoma: Prognostic factors for development of distant metastases and oncological outcomes

Cited by 2 publications

References 40 publications

Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration

Long-read sequencing of oropharyngeal squamous cell carcinoma tumors reveal diverse patterns of high-risk Human Papillomavirus integration

Thyroid cartilage infiltration in advanced laryngeal cancer: prognostic implications and predictive modelling

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