The prognosis of oral epithelial dysplasia and oral squamous cell carcinoma in individuals with oral lichen planus: a single-centre observational study and a pioneer preliminary exploration of UK national Electronic Health Records

Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem worldwide due to its high mortality and morbidity. A notable proportion of HNSCC, particularly oral squamous cell carcinoma (OSCC), is preceded by several long-standing chronic oral mucosal diseases including oral lichen planus (OLP). However, it remains largely unknown regarding the impact of a pre-existing OLP upon the prognosis and behaviour of OSCC and its precursor, oral epithelial dysplasia (OED). Therefore, this PhD thesis has sought to determine the influence of OLP on the long-term behaviour and prognosis of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) using data from a single UK tertiary care centre. Additionally, this thesis has made the first steps towards providing understanding of the epidemiology of HNSCC in a representative sample with common chronic oral mucosal conditions including oral lichen planus, oral submucous fibrosis, leukoplakia and periodontal diseases of the UK population. A retrospective cohort study of 299 patients with OED revealed that individuals with OED arising on a background of OLP appeared to be at higher risk of developing new primary OEDs up to 3 years (in the early years) after the first diagnosis of OED compared to those without OLP. However, the risk of malignant progression was similar between the two groups. This thesis built on these findings by investigating the impact of OLP in determining the long-term behaviour and prognosis of OSCC using a retrospective cohort study of 285 patients with OSCC. The results indicated that patients with OSCC-associated OLP were more likely to develop multiple and multifocal new primary dysplastic and OSCC events following their first oral malignancy. Despite this, there seems to be no significant association between OLP and mortality. In order to reveal more about the relationship between long-standing oral mucosal conditions and HNSCC using national-scale data, this thesis went beyond single data sources. This project provides a detailed method for appropriate data handling and curation of a linked national database of a UK population (the CALIBER platform). This allowed the development and validation of a reliable phenotype algorithm to identify patients with HNSCC from this data platform. Taken together, these findings advance understanding of the impact of OLP on the behaviour and prognosis of OED and OSCC. In addition, the HSNCC phenotype algorithm developed here represents an important step towards understanding the association between common chronic oral mucosal conditions and HNSCC in the UK

Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy, and mortality. Cox proportional hazard and Poisson regression models were performed. RESULTS: 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED) were included. A pre-existing diagnosis of OLP was significantly associated with a 2-fold increased risk of subsequent primary OED events (HR=2.02, p=0.04), which also developed faster (1.46 vs 2.96 years, p=0.04) and with more involvement of non-cancer prone sites (p=0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. CONCLUSIONS: OLP/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality

Osteonecrosis of the Jaw Associated with Antiangiogenics in Antiresorptive-Naïve Patient: A Comprehensive Review of the Literature

Objectives. To review the available literature on medication-related osteonecrosis of the jaw (MRONJ) associated with antiangiogenics in antiresorptive-naïve individuals. Methods. A literature search was performed using MEDLINE via PubMed, EMBASE, and Web of Science in December 2017. Results. We identified reports describing a total of 35 antiresorptive drugs-naïve patients who developed antiangiogenic-related MRONJ. The mean age of these patients was 59.06 years and the F : M ratio was 4 : 5. The most common underlying disease was metastatic renal cell cancer. Pain to the mandible was the most common complaint (34.29%) and the majority of patients presented with bone exposure. The mean duration of intravenous and oral antiangiogenics before MRONJ development was 6.5 and 16.72 months, respectively. The most common additional risk factor was dental extraction (37.14%). Almost half of the MRONJ patients (48.57%) received surgical treatment. 18 patients (62.06%) were reported to have disease resolution within an average time of 6.75 months. Conclusion. MRONJ associated with antiangiogenic therapy in antiresorptive-naïve patients is a rare but potentially serious adverse effect. Available data suggests that there might be notable differences between MRONJ associated with antiangiogenics and antiresorptives; however, further prospective well-designed studies are required