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2. Hallmarks of a genomically distinct subclass of head and neck cancer

Author

Muijlwijk, Tara, Nauta, Irene H., van der Lee, Anabel, Grünewald, Kari J. T., Brink, Arjen, Ganzevles, Sonja H., Baatenburg de Jong, Robert J., Atanesyan, Lilit, Savola, Suvi, van de Wiel, Mark A., Peferoen, Laura A. N., Bloemena, Elisabeth, van de Ven, Rieneke, Leemans, C. René, Poell, Jos B., and Brakenhoff, Ruud H.

Published
2024
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5. TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma

Author

von Buchwald, Christian, Jakobsen, Kathrine Kronberg, Carlander, Amanda-Louise Fenger, Tous, Sara, Grønhøj, Christian, Rasmussen, Jacob H., Brooks, Jill, Taberna, Miren, Mena, Marisa, Morey, Francisca, Bruni, Laia, Batis, Nikolaos, Brakenhoff, Ruud H., René Leemans, C., Jong, Robert J.Baatenburg de, Klussmann, Jens Peter, Wuerdemann, Nora, Wagner, Steffen, Dalianis, Tina, Marklund, Linda, Mirghani, Haïtham, Schache, Andrew, James, Jaqueline A., Huang, Shao Hui, O’Sullivan, Brian, Nankivell, Paul, Broglie, Martina A., Hoffmann, Markus, Quabius, Elgar Susanne, Anderson, Lesley A., Craig, Stephanie G., Alemany, Laia, and Mehanna, Hisham

Published
2024
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7. Genome-wide siRNA screens identify RBBP9 function as a potential target in Fanconi anaemia-deficient head-and-neck squamous cell carcinoma

Author

Pai, Govind, Roohollahi, Khashayar, Rockx, Davy, de Jong, Yvonne, Stoepker, Chantal, Pennings, Charlotte, Rooimans, Martin, Vriend, Lianne, Piersma, Sander, Jimenez, Connie R., De Menezes, Renee X., Van Beusechem, Victor W., Brakenhoff, Ruud H., Te Riele, Hein, Wolthuis, Rob M. F., and Dorsman, Josephine C.

Published
2023
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9. HeNeCOn: An ontology for integrative research in Head and Neck cancer

Author

Poli, Tito, Rossi, Silvia, Martinelli, Elena, Licitra, Lisa, Cavalieri, Stefano, De Cecco, Loris, Canevari, Silvana, Scheckenbach, Kathrin, Brakenhoff, Ruud H., Nauta, Irene, Hoebers, Frank J.P., Wesseling, Frederik W.R., Trama, Annalisa, Gatta, Gemma, Hernández, Liss, Estévez-Priego, Estefanía, López-Pérez, Laura, Fernanda Cabrera-Umpiérrez, María, Arredondo, María Teresa, and Fico, Giuseppe

Published
2024
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10. The course of health-related quality of life in the first 2 years after a diagnosis of head and neck cancer: the role of personal, clinical, psychological, physical, social, lifestyle, disease-related, and biological factors

Author

Verdonck-de Leeuw, Irma M., Korsten, Laura H.A., van Nieuwenhuizen, Annette, Baatenburg de Jong, Rob J., Brakenhoff, Ruud H., Buffart, Laurien M., Lamers, Femke, Langendijk, Johannes A., Leemans, C. René, Smit, Jan H., Sprangers, Mirjam A., Takes, Robert P., Terhaard, Chris H. J., Lissenberg-Witte, Birgit I., and Jansen, Femke

Published
2023
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12. Study retention and attrition in a longitudinal cohort study including patient-reported outcomes, fieldwork and biobank samples: results of the Netherlands quality of life and Biomedical cohort study (NET-QUBIC) among 739 head and neck cancer patients and 262 informal caregivers

Author

Jansen, Femke, Brakenhoff, Ruud H., Baatenburg de Jong, Rob J., Langendijk, Johannes A., Leemans, C. René, Takes, Robert P., Terhaard, Chris H. J., Smit, Jan H., and Verdonck-de Leeuw, Irma M.

Published
2022
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14. Architectural dysplasia in surgical margins and the risk of local relapse in oral cancer.

Author

Nauta, Irene H., Peferoen, Laura A. N., Brakenhoff, Ruud H., Leemans, C. René, and Bloemena, Elisabeth

Subjects
SQUAMOUS cell carcinoma, CANCER relapse, SURGICAL margin, DYSPLASIA, ORAL cancer
Abstract

Background: A major challenge in the clinical management of oral cavity squamous cell carcinoma is local relapse. Even when surgical margins are tumor‐free, local relapses occur frequently, and relapse prediction by histology remains suboptimal. In leukoplakia, an oral potentially malignant disorder, the presence of architectural dysplasia is a critical risk factor for malignant transformation. This study aimed to investigate whether the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is a risk factor for local relapse. Methods: Hematoxylin and eosin‐stained slides of resection margins from a consecutive cohort of surgically treated patients diagnosed with stage I–IV oral cavity squamous cell carcinoma between 2008 and 2014 were assessed for the presence of architectural dysplasia (N = 311). Five‐year local relapse‐free survival rates of oral cavity squamous cell carcinoma with architectural dysplasia were compared to those of oral cavity squamous cell carcinoma without architectural dysplasia. Results: In total, 92 of 311 (29.6%) of oral cavity squamous cell carcinoma displayed architectural dysplasia in the margins. The presence of architectural dysplasia was associated with higher patient age, female sex, less pack years, lower cT‐stage, and a cohesive tumor growth pattern. In oral cavity squamous cell carcinomas with architectural dysplasia, postoperative (chemo)radiotherapy was less often indicated compared with oral cavity squamous cell carcinoma without architectural dysplasia (19.5% vs. 36.1%, p = 0.009). Five‐year local relapse‐free survival was significantly lower in oral cavity squamous cell carcinoma with architectural dysplasia than in oral cavity squamous cell carcinoma without architectural dysplasia (83.1% vs. 94.9%, p = 0.017). Conclusions: Oral cavity squamous cell carcinoma arising in the background of architectural dysplasia displays relatively favorable clinical and histopathological characteristics. Nonetheless, the presence of architectural dysplasia in oral cavity squamous cell carcinoma surgical margins is associated with a higher risk of local relapse, indicating its clinical relevance. [ABSTRACT FROM AUTHOR]

Published
2024
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17. The value of regular follow‐up of oral leukoplakia for early detection of malignant transformation.

Author

Evren, Ilkay, Najim, Ahmad M., Poell, Jos B., Brouns, Elisabeth R., Wils, Leon J., Peferoen, Laura A. N., Brakenhoff, Ruud H., Bloemena, Elisabeth, van der Meij, Erik H., and de Visscher, Jan G. A. M.

Subjects
SQUAMOUS cell carcinoma, PEARSON correlation (Statistics), MOUTH tumors, T-test (Statistics), DATA analysis, EARLY detection of cancer, FISHER exact test, ORAL leukoplakia, RETROSPECTIVE studies, MANN Whitney U Test, CHI-squared test, DESCRIPTIVE statistics, MEDICAL records, ACQUISITION of data, STATISTICS, DATA analysis software, PATIENT aftercare, DISEASE progression
Abstract

Objectives: Evaluate whether regular follow‐up of oral leukoplakia (OL) resulted in early detection of malignant transformation (MT). Method: Two hundred and twenty‐two consecutive patients with OL (147 females, 75 males); median follow‐up period of 64 months (range: 12–300). Three groups were distinguished: group A (n = 92) follow‐up at the hospital; group B (n = 84) follow‐up by their dentist; group C (n = 46) lost to follow‐up. Results: OLs in group B compared to group A, were smaller in size (<2 cm; p < 0.001), showed more hyperkeratosis (p < 0.001) and less moderate/severe dysplasia (p < 0.001). MT occurred in 45 (20%) patients: 32 (35%) in group A, five (6%) in group B and eight (17%) in group C. There was no significant difference in clinical tumour size between group A (median: 15 mm, range: 1–40) and group B (median: 10 mm, range: 3–25; p = 0.496). Tumour size was smaller for patients in groups A and B (median: 10 mm, range 1–40) compared to group C (median: 33 mm, range: 3–100; p = 0.003). There was a positive correlation between tumour size and interval between the last visit in all patients (p = 0.022). Conclusion: Regular follow‐up of OL resulted in early detection of MT. If properly selected, follow‐up of OL performed by the dentist seems feasible. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Genomic Engineering of Oral Keratinocytes to Establish In Vitro Oral Potentially Malignant Disease Models as a Platform for Treatment Investigation.

Author

Wils, Leon J., Buijze, Marijke, Stigter-van Walsum, Marijke, Brink, Arjen, van Kempen, Britt E., Peferoen, Laura, Brouns, Elisabeth R., de Visscher, Jan G. A. M., van der Meij, Erik H., Bloemena, Elisabeth, Poell, Jos B., and Brakenhoff, Ruud H.

Subjects
KERATINOCYTE differentiation, DYSPLASIA, KERATINOCYTES, ORAL leukoplakia, ORAL mucosa, SMALL molecules, CELL lines, CELL culture
Abstract

Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments are urgently awaited. Here, we generated precancer culture models using a previously established method for the generation of oral keratinocyte cultures and incorporated CRISPR/Cas9 editing. The generated cell lines were used to investigate the efficacy of a set of small molecule inhibitors. Tumor-adjacent mucosa and oral leukoplakia biopsies were cultured and genetically characterized. Mutations were introduced in CDKN2A and TP53 using CRISPR/Cas9 and combined with the ectopic activation of telomerase to generate cell lines with prolonged proliferation. The method was tested in normal oral keratinocytes and tumor-adjacent biopsies and subsequently applied to a large set of oral leukoplakia biopsies. Finally, a subset of the immortalized cell lines was used to assess the efficacy of a set of small molecule inhibitors. Culturing and genomic engineering was highly efficient for normal and tumor-adjacent oral keratinocytes, but success rates in oral leukoplakia were remarkably low. Knock-out of CDKN2A in combination with either the activation of telomerase or knock-out of TP53 seemed a prerequisite for immortalization. Prolonged culturing was accompanied by additional genetic aberrations in these cultures. The generated cell lines were more sensitive than normal keratinocytes to small molecule inhibitors of previously identified targets. In conclusion, while very effective for normal keratinocytes and tumor-adjacent biopsies, the success rate of oral leukoplakia cell culturing methods was very low. Genomic engineering enabled the prolonged culturing of OL-derived keratinocytes but was associated with acquired genetic changes. Further studies are required to assess to what extent the immortalized cultures faithfully represent characteristics of the cells in vivo. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Author

Cavalieri, Stefano, Serafini, Mara S., Carenzo, Andrea, Canevari, Silvana, Brakenhoff, Ruud H., Leemans, C. René, Nauta, Irene H., Hoebers, Frank, van den Hout, Mari F. C. M., Scheckenbach, Kathrin, Hoffmann, Thomas K., Ardighieri, Laura, Poli, Tito, Quattrone, Pasquale, Locati, Laura D., Licitra, Lisa, and De Cecco, Loris

Published
2021
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30. Privacy-preserving distributed learning of radiomics to predict overall survival and HPV status in head and neck cancer

Author

Bogowicz, Marta, Jochems, Arthur, Deist, Timo M., Tanadini-Lang, Stephanie, Huang, Shao Hui, Chan, Biu, Waldron, John N., Bratman, Scott, O’Sullivan, Brian, Riesterer, Oliver, Studer, Gabriela, Unkelbach, Jan, Barakat, Samir, Brakenhoff, Ruud H., Nauta, Irene, Gazzani, Silvia E., Calareso, Giuseppina, Scheckenbach, Kathrin, Hoebers, Frank, Wesseling, Frederik W. R., Keek, Simon, Sanduleanu, Sebastian, Leijenaar, Ralph T. H., Vergeer, Marije R., Leemans, C. René, Terhaard, Chris H. J., van den Brekel, Michiel W. M., Hamming-Vrieze, Olga, van der Heijden, Martijn A., Elhalawani, Hesham M., Fuller, Clifton D., Guckenberger, Matthias, and Lambin, Philippe

Published
2020
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35. The role of differentiated dysplasia in the prediction of malignant transformation of oral leukoplakia.

Author

Wils, Leon J., Poell, Jos B., Peferoen, Laura A. N., Evren, Ilkay, Brouns, Elisabeth R., de Visscher, Jan G. A. M., van der Meij, Erik H., Brakenhoff, Ruud H., and Bloemena, Elisabeth

Subjects
ORAL leukoplakia, DYSPLASIA, DISEASE risk factors, SQUAMOUS cell carcinoma
Abstract

Objective: Oral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO‐defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients. Method: For this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter‐observer agreement for the diagnosis of differentiated dysplasia was determined. Results: In total, 33 of 176 patients developed oral squamous cell carcinoma during follow‐up. Presence of classic epithelial dysplasia increased cancer risk two‐fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk‐stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven‐fold increased risk of malignant transformation (7.34, p = 0.001). Inter‐observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001). Discussion: This study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Oral leukoplakia classification and staging system with incorporation of differentiated dysplasia.

Author

Brouns, Elisabeth R., Evren, Ilkay, Wils, Leon J., Poell, Jos B., Brakenhoff, Ruud H., Bloemena, Elisabeth, and de Visscher, Jan G. A. M.

Subjects
ORAL leukoplakia, NEOPLASTIC cell transformation, RETROSPECTIVE studies, TUMOR classification, CANCER patients, DESCRIPTIVE statistics, CHI-squared test, KAPLAN-Meier estimator, DATA analysis software
Abstract

Objectives: A classification and staging system for oral leukoplakia (OL) was introduced to promote uniform reporting. In this system, size and the histopathologic diagnosis are assessed and combined in a staging system. The various stages could be predictive for malignant transformation of OL. Differentiated dysplasia (DD) was recently recognized as an important architectural pattern of dysplasia and is highly associated with malignant transformation (MT) of OL. In the present study, DD was incorporated in the OL‐system. The aim of the present study was to test the adapted system on a cohort of patients with OL. Patient and methods: The group consisted of 140 patients. The size, absence or presence and degree of classic dysplasia (CD) and DD were incorporated into the OL‐system. Results: In 31/140 patients, MT occurred. Size was not statistically significant with MT (p = 0.422). The presence of dysplasia was predictive for MT (p = 0.003), whereby severe CD and DD were highly statistically significant for MT (p = 0.008). Stage IV was statistically significant for MT (p = 0.011). Conclusions: The present study emphasizes the value of the slightly modified OL‐system with incorporation of DD in uniform reporting of OL and the value in predicting MT. [ABSTRACT FROM AUTHOR]

Published
2023
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42. Molecular screening of oral precancer

Author

Graveland, A. Peggy, Bremmer, Jantine F., de Maaker, Michiel, Brink, Arjen, Cobussen, Paul, Zwart, Meindert, Braakhuis, Boudewijn J.M., Bloemena, Elisabeth, van der Waal, Isaäc, Leemans, C. René, and Brakenhoff, Ruud H.

Published
2013
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46. Associations between clinical and histopathological characteristics in oral leukoplakia.

Author

Evren, Ilkay, Brouns, Elisabeth R., Poell, Jos B., Wils, Leon J., Brakenhoff, Ruud H., Bloemena, Elisabeth, and de Visscher, Jan G.A.M.

Subjects
ORAL leukoplakia, BIOPSY, TONGUE, ODDS ratio
Abstract

Objectives: To identify possible associations between patients' demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients' first visit. Method: A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated. Results: A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size <2cm and non‐homogeneous OLs (42%) with non‐smokers. No dysplasia was present in 40% and any dysplasia (AD) in 60%. Tongue OLs were correlated with AD (OR:6.0) and CD (OR:5.7). FOM OLs were correlated with CD (OR:4.5). DD was correlated with non‐homogeneous OLs (OR:2.6). Conclusions: CD was most frequently observed in tongue and FOM OLs, while DD was associated with non‐homogeneous OLs. In this series of patients, there was no consistent reliable association between the clinical and histopathological features and clinical characteristics can therefore not substitute microscopic examination of biopsies. [ABSTRACT FROM AUTHOR]

Published
2023
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