Short summary

Early cancer or a premalignant lesion (LIN) on the vocal cords may appear as a non-neoplastic benign inflammatory or hyperplastic lesion, under white light. Even small tissue samples from the vocal cords may cause chronic voice problems and impair the outcome of later surgical treatment. The challenge is to choose the right treatment, without knowing the exact diagnose and therefore, correct pre-surgical assessment is extremely important. Our study will provide valuable information for future patient care, by investigating the accuracy of available diagnostic methods and histopathological evaluation, as well as knowledge of incidence of LIN in Denmark. A national collaboration concerning early cancer and LIN was established in 2012, and the present PhD study is one of several planned research projects. 

Rationale

Almost half of all laryngeal cancers occur on the vocal cords (the "glottis"). Transformation of normal mucosa into premalignant lesions ("dysplasia" or "LIN") and cancer is a multistage process. LIN or early cancer often appears as a white or red area on the vocal cord. Unfortunately a non-neoplastic, completely benign lesion may look similar. The incidence of LIN is unknown but expected to be increasing. Several different classification-systems are used.

In 2012 Danish national guidelines for handling of LIN and early glottic cancer were agreed. This implied a completely new treatment strategy in Denmark. Until then, all cancers were treated by radiotherapy. LIN were often biopsied and then laser-evaporated at a second operation.

A new one-stage surgical technique is now recommended. This allows histological evaluation of the entire lesion as well as sufficient surgical treatment in case of LIN or early cancer. Punch biopsy must be avoided, because deeper resection then is required to cure the patient.

Surgery may result in chronic, severe hoarseness, if the deep layers of the mucosa are harmed. Careful surgical technique is essential. The basal layers must remain untouched, unless the lesion invades it. Completely benign lesions are often best treated conservatively, and surgery kept for persistent lesions.

The challenge is to choose the right treatment, without knowing the exact diagnose. Correct pre-surgical assessment is therefore extremely important. However, information concerning the accuracy of existing pre-surgical methods is inadequate

Our study will provide essential information for future treatment planning and patient care by

1. investigating if available pre-surgical diagnostic methods can differentiate LIN or cancer from non-neoplastic benign glottic lesions
2. evaluating inter- and intraobserver variation of the two most well-documented classification-systems of premalignant glottic lesions
3. estimating incidence and malignant transformation rate for LIN in the western part of Denmark

The present study is based on a national database. Several additional projects concerning different aspects of early glottis cancer and LIN are planned.

Description of the cohort

1. Patients with a glottic lesion, suspected to represent LIN or early glottic cancer, referred to a tertiary ENT department for evaluation and subsequent surgical treatment from 1.9.2012 to 31.12.2017.
2. 200 anonymized histopathological slides from tissue samples previously classified as representing a premalignant lesion
3. Patients with histopathologically verified LIN identified by a systematic search in the Danish National Pathology Register from 1.1.2000 to 31.12.2009. 

Data and biological material

1. Prospective data collection (demographic data, smoking status, alcohol use, symptoms, previous surgery on vocal cords, description of glottis lesion, diagnostic methods applied, date of surgery, voice analysis, expected diagnose, surgical procedure, histopathology , follow-up, recurrence) 
2. Independent evaluation by 2 pathologists of 200 anonymized histopathological slides from tissue samples previously classified as representing a premalignant lesion. Use of k-statistics to assess the degree of inter- and intraobserver agreement.
3. Patients with histopathologically verified LIN identified by a systematic search in the Danish National Pathology Register from 1.1.2000 to 31.12.2009 and subsequently retrospective data collection from chart review (demographic data, smoking status, previous surgery on vocal cords, description of glottis lesion, date and details of surgery, histopathology, recurrence date and histopathological evaluation)

Collaborating researchers and departments

Department of Otolaryngology, Odense University Hospital Institute of clinical research, University of Southern Denmark

• Professor and Consultant Christian Godballe

Department of Otolaryngology, Aarhus University Hospital Institute of clinical research, Aarhus University

• Consultant and Clinical Associate Professor Thomas Kjærsgaard, PhD

Department of Otolaryngology, Aalborg University Hospital

• Consultant Kirsten Hald

Department of Otolaryngology, Copenhagen University Hospital

Rigshospitalet Institute of clinical research, Copenhagen University, Denmark

• Consultant and Clinical Associate Professor Jesper Filtenborg Tvedskov, PhD