Neoplasms

All Conditions

Mouth and Tooth Diseases

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Lichen Planus, Oral

Lichen Planus

Mouth Neoplasms

Leukoplakia

Leukoplakia, Oral

Lichenoid Eruptions

Exanthema

Skin Diseases

Skin Diseases, Papulosquamous

Mouth Diseases

Stomatognathic Diseases

Precancerous Conditions

Pathological Conditions, Anatomical

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

Oral Cancer

Lip and Oral Cavity Cancer

Oral Leukoplakia

Manuel Weber, MD, DMD

Falk Wehrhan, MD, DMD

Jutta Ries, PhD

Oral squamous cell carcinomas (OSCC) is among the most common malignancies worldwide. Early detection and prevention of OSCC is thought to have the highest potential to reduce morbidity and mortality. In prevention, the main focus is on precancerous lesions, especially oral leukoplakia (OLP), as up to 67% of OSCC arise on the basis of OLP. The determination of the transformation risk of OLP by histological determination of the degree of dysplasia is unreliable.

A promising marker for the timely development of a OSCC is the detection of antigens of the MAGE-A gene family. The special feature of MAGE-A is that they can be detected in 93% of all OSCC and in approx. 85% of OLP that transform to OSCC. The detection of MAGE-A could also indicate changes in the immunological environment that occur prior to malignant OLP transformation and could be used for immunotherapies.

Aim of this study is to investigate MAGE-A as a predictive marker for the malignant transformation of OLP in the setting of a prospective, multicenter study and to establish it as a diagnostic parameter in addition to classical histology. In addition, the association of MAGE-A expression with the occurrence of immunological changes in OLP will be investigated in order to evaluate the possibility of minimally invasive immunotherapy of OLP.

The study is intended to include 500 biopsies of non-selected patients with OLP from university institutions and private practices. The follow-up should be at least 3 years, whereby it is examined whether an OSCC on the basis of the original OLP developed. After three years, an interim evaluation of the results with statistical evaluation will be carried out. In order to ensure that the course of the disease is monitored for at least three years for all OLPs, an extension of the monitoring period to 5 years is planned.

The study could establish a routine diagnostic parameter to supplement the histo-morphological diagnosis of OLP and evaluate the possibility of immunotherapy of OLP.

Oral squamous cell carcinomas (OSCC) is among the most common malignancies worldwide. Despite the introduction of microsurgical reconstruction options and advances in multimodal tumor therapy, the prognosis has not improved significantly in the last 30 years.

The most important aspect for increasing survival rate is seen in the early detection of OSCC and its precursor lesions. Up to 67 % of OSCC develop on the basis of oral leukoplakia (OLP), which frequently occur prior to the diagnosis of carcinoma. OLP treatment depends on the risk of malignant transformation. Therapeutic approaches range from simple observation to complete surgical excision of OLP. The scientific evidence regarding the handling of OLP is low. Current literature outlines missing evidence in therapeutic management of OLP. The early identification of OLP with a high risk of malignant degeneration is a relevant clinical question, since approx. 2% of OLPs transform malignantly each year. In lesions with dysplasia this rate increases to about 17%.

Gold standard for determining the risk of malignant transformation of OLP is the histologic determination of the degree of dysplasia. As the histological degree of dysplasia increases, so does the risk of developing PECM on the basis of OLP. The decision for a surgical or a conservative therapy currently depends on the degree of dysplasia of the OLP. The histopathological assessment of the degree of dysplasia is subjective and depends on the experience of the pathologist making the assessment. However, the major disadvantage in assessing the malignant transformation potential with this method is that many precursor lesions do not follow the histopathologically determined degree of dysplasia. Thus, 0-3% of hyperplasias (D0) and up to 30% of mild dysplasias (D1) transform to OSCC. D0 OLP are lesions, which are usually only observed according to current therapy recommendations. Thus, an assessment of the dignity of OLP and a long-term prediction of the risk for the development of OSCC are not reliable. OLP with a histopathologically low malignancy potential but a cell-biologically probable malignant transformation must be identified in order to prevent undertreatment of these patients.

The aim of this explorative study is to investigate whether the malignant transformation of OLP can be reliably predicted using immunohistochemical and molecular biological methods. A significant association of the expression of MAGE-A expression with the malignant transformation of OLP to OSCC has already been demonstrated in retrospective studies. It is now necessary to further develop these available test procedures and evaluate them in a prospective study in order to transfer them into clinical routine. Sensitivity and specificity of the investigated markers will be investigated in a prospective, multicenter setting. A non-selected group of patients will be examined. The aim is to establish a test procedure that can be used cost-effectively. The MAGE-A expression should serve as an indicator and for the application of new, innovative therapy concepts such as the immunotherapy of OLP.

The following questions will be answered:

i) Do OLP with malignant transformation show an increased MAGE-A expression in a time interval of 3 years (follow-up up to 5 years)? ii) How high is the sensitivity and specificity of MAGE-A expression as a predictive diagnostic test? Is immunohistochemical or molecular biological (RT-PCR) detection of MAGE-A better suited as a diagnostic test? iii) Can MAGE-A be used successfully as a diagnostic test in practice? iv) Is there an association between MAGE-A expression and immunological changes preceding malignant transformation (macrophage polarization, T cell infiltration, checkpoint expression, TLR expression)? v) Are the immunological changes in OLP potentially amenable to immunomodulatory therapy?

Short summary of the study protocol:

After the patient has been informed and included in the study, the first step is the photo documentation and then the incision biopsy of the OLP. The treating physician is free to choose whether to take a sample from one or more sites of the lesion. This procedure complies with the standard diagnostic guidelines and is not a study-specific measure. Thus, there is no deviation from the clinical routine for the study and no invasive measure required by the study. The sample taken is then divided. The total amount of tissue taken corresponds to the amount taken in the routine outside the study. One part of the sample is conventionally fixed in formalin. The second part (max. 5x5x2mm) is preserved in RNA later for later PCR analysis. Both samples will be sent to the study center in Erlangen. There the histological evaluation of the tissue takes place in the Pathological Institute of the University Hospital Erlangen within routine diagnostics. The result is communicated to the treating physician and the study centre. The immunohistochemical and molecular biological analyses are carried out in the laboratories of the Oral and Maxillofacial Surgery Erlangen. The results of the analyses are not communicated to the attending physician (blinding). A therapy decision is only made on the basis of clinical and classical histological parameters (degree of dysplasia). D0 and D1 lesions are monitored. D2 and D3 lesions are treated surgically or with laser coagulation depending on the decision of the treating physician and patient. This corresponds to the current clinical standard. If the patient rejects the treatment of the lesion and wishes to continue observing its progress, he remains included in the study. The follow-up time during the study period is 3 years (evaluations also after 2 years). After completion of the study a further follow-up of 2 years is planned in order to achieve a total follow-up of 5 years.

paraffin specimens and RNAlater specimens

Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore

Prospective Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore

Association of OLP malignant transformation with a MAGE-A based immunoscore. Into this score, the following immunohistochemical and molecular biological parameters determined in biopsies will be integrated:

* MAGE-A expression
* Macrophage infiltration and polarization (CD68, CD163)
* T cell infiltration (CD3, CD8)
* Altered expression of immune checkpoints and TLR receptors (PD-L1, PD-L2, TLR7) These parameters will be aggregated to an immunoscore

Frequency of malignant transformation of OLP (determination of the incidence of OSCC in OLP cases)

Dependence of malignant transformation on histologically determined degree of dysplasia (D0-D3)

University of Erlangen-Nürnberg Medical School

Dr. med. Dr. med. dent. Manuel Weber, MD, DMD, Principal Investigator

Infections

Behaviors and Mental Disorders

Fibrosis

Hyperplasia

Candidiasis

Oral Submucous Fibrosis

Erythroplasia

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Quality of Life

Chronic Graft Versus Host Disease

Erythroplakia

INCLUSION CRITERIA

These include:

* Adults aged 18 or above at the time of the screening visit.
* Good command of English language both written and spoken \[this is necessary as questionnaires are in English and cannot be translated unless through a cross-cultural validation study\].
* Being able to consent.
* Diagnosed with OED as per current standard diagnostic criteria.
* No concurrent malignancy in the head and neck or elsewhere.

No intervention was/is planned for this study. The study is questionnaire-based (observational).

No intervention is planned for this study

Background: Oral epithelial dysplasia (OED) is a condition with an increased risk of oral cancer. Due to the current changes in the factors associated with these diseases (because of human papillomavirus), it is expected that those who have no history of smoking or alcohol, young (\<50 years old), and white male would be commonly affected. Those individuals require a higher need for information, preferred a more active role in decision-making, and have a longer lifespan than older individuals. There remain no detailed studies of whether the informational needs delivered to patients with OED met their needs or indeed what information such patient may wish. A few tools are available to evaluate the IN of patients with head and neck disorders. However, the items of these instruments were dedicated to a particular disease (e.g. cancer) and hence are not applicable to be used for OED.

Project aims: To evaluate the psychometric properties of the Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q), developed and revised in the preliminary work for the proposed study, in a cohort of patients with OED.

Timescale: 19 months.

Clinical significance: This questionnaire can be useful in clinical practice. It could help to meet the patient's information needs and plan educational interventions for those showing unmet needs.

Oral epithelial dysplasia (OED) is a disease associated with an increased risk of oral cancer between 6% and 36% compared to disease-free individuals. In the United Kingdom, oral cancer is among the 15 most common cancers, with approximately 6,000 new cases per year and these numbers are expected to rise in the few coming years.

Research showed the importance of patient education and the provision of information in shared-decision making and management of chronic and cancer-linked disease such as perhaps OED. However, patients may not be satisfied with the information provided by healthcare professionals, despite the extensive nature of the information provided. Having unmet informational needs may associate with higher anxiety levels which in turn could affect the patient's well-being and cooperation with the treatment provided.

Avoiding these undesirable health outcomes requires the delivery of tailored and patient-centred care that provides information based on what patients truly need and prefer. One increasingly common method to do so is to obtain this information by informational needs questionnaires. These questionnaires have been developed for other medical conditions including chronic diseases and some cancers, but none of these is known to be appropriate to use for OED specifically. Hence, a specific tool to determine the informational needs and preferences of patients with OED may help to achieve these objectives effectively. The data collected by this tool may help to acknowledge the impact of the illness on physical and psychological well-being. Furthermore, this data could be used to produce a source of OED information (such as a patient information leaflet) that reflects the IN of this patient population.

In the preliminary work for this study, the Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q) was developed by adopting existing valid and reliable instruments that explore the information need of patients with potentially malignant disease elsewhere in the body, using experts input. The questions were then formulated and tested for content validity by clinicians (n=12) and patients (n=5), with unclear, irrelevant, redundant, and unacceptable items omitted. The final 35-item ODIN-Q includes two scales: (1) amount of information already received (too much, enough, not enough and none) and (2) degree of importance of the information (very, yes, not very, not at all).

Thus, the objectives of this study are to (1) test the newly developed ODIN-Q in a cohort of patients with OED; (2) to investigate the correlations between patients' informational needs and both of psychological variables (e.g. anxiety and depression) and quality of life; and (3) to develop and a Patient Information Leaflet (PIL) for OED based on patients' needs and preferences.

Oral Epithelial Dysplasia Informational Needs Questionnaire

Development of an Oral Epithelial Dysplasia Informational Needs Questionnaire

To evaluate the psychometric properties of the Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q), developed and revised in the preliminary work for the proposed study, in a cohort of patients with OED (Phase 1).

To investigate the correlation between psychological variables (e.g. anxiety and depression), quality of life (QoL) and information needs by analysis of the data collected by ODIN-Q, Krantz Health Opinion Survey, Hospital Anxiety and Depression Scale, Modified Dental Anxiety Scale and the Oral Health Impact Profile-14 (phase 1).

To develop and assess the satisfaction with a patient information leaflet \[PIL\] about OED (phase 2).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore	NCT03975322	Oral Leukoplaki... Oral Leukoplaki... Oral Leukoplaki... Oral Lichen Pla...		18 Years - 80 Years	University of Erlangen-Nürnberg Medical School
Oral Epithelial Dysplasia Informational Needs Questionnaire	NCT04153266	Oral Epithelial... Precancerous Co... Precancerous Le... Oral Lichen Pla... Oral Leukoplaki... Oral Leukoplaki... Oral Leukoplaki... Oral Leukoplaki... Oral Erythropla... Chronic Hyperpl... Oral Submucous ... Oral Submucosal... Oral Disease Dental Diseases Dysplasia Information See... Patient Prefere... Information Nee... Health Behavior Quality of Life Preference, Pat... Patient Satisfa... Patient Engagem... Patient Partici...	No intervention...	18 Years -	University College, London
Prediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore	NCT03975322	Oral Leukoplaki... Oral Leukoplaki... Oral Leukoplaki... Oral Lichen Pla...		18 Years - 80 Years	University of Erlangen-Nürnberg Medical School

Spots Global Cancer Trial Database for oral leukoplakia of tongue