Predictive value of tumor budding in head and neck squamous cell carcinoma: an update

Chiesa-Estomba, Carlos M.; Thompson, Lester; Agaimy, Abbas; Zidar, Nina; Simpson, Roderick H. W.; Franchi, Alessandro; Rodrigo, Juan P.; Mäkitie, Antti A.; Almangush, Alhadi; Leivo, Ilmo; Ferlito, Alfio

doi:10.1007/s00428-023-03630-6

Cited by 6 publications

(3 citation statements)

References 89 publications

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“…Beyond the aforementioned criteria, several factors such as tumor budding [ 43 – 45 ], stromal reactions (including desmoplasia and local immune responses) [ 46 ], the tumor-stroma ratio [ 47 , 48 ], the presence of myofibroblasts [ 49 ], and cancer-associated fibroblasts [ 50 ] may merit consideration for inclusion in the next generation of staging.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Struckmeier,

Eichhorn,

Agaimy

et al. 2024

Virchows Arch

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Since its introduction in 1968, the TNM (tumor, node, metastasis) classification established by the International Union Against Cancer has provided a consistent framework for staging of oral squamous cell carcinoma (OSCC). The introduction of the 8th edition in 2017 brought about significant modifications, encompassing the integration of depth of invasion (DOI) and extranodal extension (ENE) into the T and N classifications. Further, the UICC the criteria for the T3 and T4a categories were amended in 2020. This study aimed to evaluate the impact of reclassification on staging and, subsequently, the survival of patients with OSCC. Primary OSCCs from 391 patients were classified according to the 7th and revised 8th UICC editions (2020). Stage migration was assessed, and stage-specific progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method. The log-rank test was used to compare the different stages. Cox-proportional hazard modeling was used to compare the two editions. Incorporating the DOI into the T classification resulted in an upstaging of 77 patients, constituting 19.69% of the cohort. In addition, 49 (12.53%) patients experienced an upstaging when considering ENE in the N classification. Consequently, 103 patients underwent upstaging in UICC staging, accounting for 21.74% of cases. Upstaging mainly occurred from stage III to IVA (26.92%) and from stage IVA to IVB (31.78%). Upon comparing the categories in survival analysis, significant differences in OS and PFS were especially observed between stage IVB and lower stages. When examining the hazard ratios, it became evident that UICC 8 stage IVB is burdened by a 5.59-fold greater risk of disease progression than stage I. Furthermore, UICC 8 stage IVB exhibits a 3.83 times higher likelihood of death than stage I disease. We demonstrated significant stage migration from the 7th to the revised 8th UICC edition. Overall, incorporating DOI and ENE into the T and N classifications represents a substantial clinical advancement, leading to a more accurate staging of OSCC patients. Both staging systems exhibited statistically significant discrimination between stages; however, the 8th UICC edition allowed for a more precise categorization of patients based on their prognosis and led to enhanced hazard discrimination, particularly within higher stages.

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Section: Discussionmentioning

confidence: 99%

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Struckmeier,

Eichhorn,

Agaimy

et al. 2024

Virchows Arch

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“…Tumor budding is characterized by isolated cells or small tumor clusters comprising fewer than five cells within the stroma present at the invasive front of the tumor ( 60 ), representing the most non-cohesive form of invasion. Studies indicate that these budding areas contain cells displaying typical epithelial-mesenchymal transition features, indicating heightened invasiveness ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Histopathological predictors of lymph node metastasis in oral cavity squamous cell carcinoma: a systematic review and meta-analysis

Alqutub,

Bakhshwin

et al. 2024

Front. Oncol.

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ObjectivesLymph node metastasis (LNM) is the most significant parameter affecting overall survival in patients with oral cavity squamous cell carcinomas (OCSCC). Elective neck dissection (END) is the standard of care in the early management of OCSCC with a depth of invasion (DOI) greater than 2-4 mm. However, most patients show no LNM in the final pathologic report, indicating overtreatment. Thus, more detailed indicators are needed to predict LNM in patients with OCSCC. In this study, we critically evaluate the existing literature about the risk of different histological parameters in estimating LNM.MethodsA systematic review was conducted using PRISMA guidelines. PubMed, Web of Science, Cochrane, and Scopus were searched from inception to December 2023 to collect all relevant studies. Eligibility screening of records was performed, and data extraction from the selected studies was carried out independently. Inclusion in our systematic review necessitated the following prerequisites: Involvement of patients diagnosed with OCSCC, and examination of histological parameters related to lymph node metastasis in these studies. Exclusion criteria included animal studies, non-English articles, non-availability of full text, and unpublished data.ResultsWe included 217 studies in our systematic review, of which 142 were eligible for the meta-analysis. DOI exceeding 4 mm exhibited higher risk for LNM [Risk ratio (RR) 2.18 (1.91-2.48), p<0.00001], as did perineural invasion (PNI) [RR 2.04 (1.77-2.34), p<0.00001], poorly differentiated tumors [RR 1.97 (1.61-2.42), p<0.00001], lymphovascular invasion (LVI) [RR 2.43 (2.12-2.78), p<0.00001], groups and single pattern of invasion [RR 2.47 (2.11-2.89), p<0.00001], high tumor budding [RR 2.65 (1.99-3.52), p<0.00001], tumor size over 4 cm [RR 1.76 (1.43-2.18), p<0.00001], tumor thickness beyond 4 mm [RR 2.72 (1.91-3.87), p<0.00001], involved or close margin [RR 1.73 (1.29-2.33), p = 0.0003], and T3 and T4 disease [RR 1.98 (1.62-2.41), p <0.00001].ConclusionOur results confirm the potential usefulness of many histopathological features in predicting LNM and highlight the promising results of others. Many of these parameters are not routinely incorporated into pathologic reports. Future studies must focus on applying these parameters to examine their validity in predicting the need for elective neck treatment.

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“…In many tumors, the TB score is associated with a worse prognosis [13][14][15][16][17][18]. There is also evidence to suggest that TB in HNSCC has a predictive benefit, with regard to different tumor localizations [19][20][21][22][23][24][25]. Almangush et al showed in a meta-analysis that the TB in oral squamous cell carcinomas (OSCC) is correlated with a high risk for lymph node metastasis (LNM), a reduced disease specific survival rate, and a reduced overall survival rate [26].…”

Section: Introductionmentioning

confidence: 99%

New Tumor Budding Evaluation in Head and Neck Squamous Cell Carcinomas

Cacchi,

Fischer,

Wermker

et al. 2024

Cancers

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Background: Tumor budding (TB) is a histomorphological characteristic of the tumor invasion front and it has an impact on the tumor outcome prediction for head and neck squamous cell carcinoma (HNSCC) aetiopathology. Patients and methods: The average TB score (TB rel) of all tumor-positive marginal sections (n = 443) in the primary tumor was analyzed in the FFPE-fixed tumor slices of 66 patients with HNSCC, and they were compared with cryo-fixed sections. Results: TB rel correlates with tumor aggressiveness (i.e., lymph node metastasis quantity, lymph node ratio, extra capsular growth, Pn1, pV1, grading). The TB scores often vary between the different tumor margins of FFPE sections in the same patient, and in many cases, they differ depending on the fixation method. Conclusion: Our data show that a randomly selected marginal cut cannot reliably mirror the TB score, and thus, they cannot predict the prognostic outcome. However, TB rel could be a tool that compensates for differences in TB score analysis. TB score determination in cryo sections seems to be inaccurate compared with TB determination in FFPE.

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Predictive value of tumor budding in head and neck squamous cell carcinoma: an update

Cited by 6 publications

References 89 publications

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Histopathological predictors of lymph node metastasis in oral cavity squamous cell carcinoma: a systematic review and meta-analysis

New Tumor Budding Evaluation in Head and Neck Squamous Cell Carcinomas

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