Jos B. Poell

Introduction: Oral potentially malignant disorders (OPMDs) have a high risk for malignant transformation. Currently the gold standard for monitoring of these lesions is through a biopsy. The aim of this study was to identify and explore potential touchpoints based on a service design perspective for improvement of the detection and monitoring of OPMDs and oral cancer. Methods: Interviews were conducted in 42 patients (oral leukoplakia (OL) and oral cancer (OC) patients), focusing on experiences within the diagnostic and monitoring process of their (pre)malignant lesions and analyzed through thematic analysis. Results: The need for innovation was most evident in several critical phases: the initial stage of symptom recognition and referral to a specialist and the ongoing monitoring phase, at the specialist and at home. Conclusion: From a patients’ perspective for both OL and OC, touchpoints for innovations are perceived to be mostly needed in the detection phase. This underlines the need for the development of diagnostic tests to support more effective, patient-centered solutions.

Overview of type of changes found in 12 target genes in 89 OL samples. Top: In the left graph the distribution of the classes of mutations is depicted. In the middle graph the type of variants is shown. In the right graph the nucleotide changes are indicated. Bottom: In the left graph the number of mutations per sample is indicated. In the middle graph the number of variant classes found per sample is shown. In the right graph the top 10 mutated genes are depicted. Del = deletion. Ins = insert. SNP = single nucleotide polymorphism. SNV = Single nucleotide variant.

Example staining of differentiated dysplasia. Differentiated dysplasia is characterized by a basal layer of small cells with hyperchromatic or open nuclei with small nucleoli with an abrupt transition to suprabasal large cells with abundant, eosinophilic cytoplasm with differences in eosinophilia, intercellular edema with clearly visible desmosomes, and large, open nuclei with prominent nucleoli.

Overview of CNA’s found in a cohort of 312 OSCC samples obtained from the TCGA database. Frequency of gains (in blue) and losses (in red) for the entire cohort are shown on the y-axis. Chromosomes are shown on the x-axis. Top 5 most frequently affected chromosome regions are indicated by black arrows.

Supplementary Table S1: Per sample sequencing characteristics; Supplementary Table S2: Co-occurrence rates and odds ratios for presence of dysplasia and investigated genomic markers.

Copy number profiles and mutations for biopsies from the oral leukoplakia and the tumor from two patients that have a different origin. For each lesion the location, the copy number profile and the mutations are shown. For each mutation the gene, the variant allele frequency (VAF) and amino acid change is indicated.

Overview of Kaplan-Meier curves for several investigated genetic markers in 89 OL samples. On the y-axis the fraction remaining free of malignant transformation over time is shown. The x-axis shows the time in years. The table below the figure specifies the number of patients at risk at the indicated timepoints for the corresponding groups. (A) Kaplan-Meier curves for presence of at least one CNA and four significant chromosome regions. (B) Kaplan-Meier curves for the presence of at least one mutation and one significantly affected gene, TP53. CNA = Copy number aberration. HR = Hazard ratio.

Overview of the inclusion of patient samples from the consecutive oral leukoplakia cohort. lcWGS = Low coverage whole genome sequencing.

Overview of laboratory methods for the processing of oral leukoplakia biopsies for next generation sequencing.