Laryngeal preneoplastic lesions and cancer: challenging diagnosis. Qualitative literature review and meta-analysis

Background: The treatment of laryngeal cancer and its precursor lesions has a great impact on important laryngeal basic functions, thus, early detection and preoperative assessment are important for a curative and function-preserving therapy. Furthermore, delayed diagnosis, leads to loco-regional failure and a high incidence of second primary tumor, reasons for poor outcome. In this setting, there are two basic clinical problems in the management of premalignant and malignant laryngeal lesions. First, small and thin lesions are difficult to evaluate by the histopathologic examination and initial biopsies are often not sufficient for a conclusive diagnosis. Second, margins of the specimens from surgical excisions are difficult to evaluate due to tissue damage from the device, leaving us in doubt whether the excision is radical or not. From these observations, it is obvious that an instrument offering the possibility to detect pre-cancerous-early cancerous lesions, and satellite foci or second primaries would be the key to improving the survival rate in head and neck cancer. But, despite the high number of more advanced diagnostic techniques and methods, unfortunately, it is not uncommon for different clinicians to use different nomenclature or to identify different stage for the same laryngeal lesion. Object. Different modalities of diagnostic techniques of laryngeal lesions exist. Rather than difference between benign and obvious malignant diseases, more difficult is to detect the presence of precancerous epithelial alterations. Not all tests achieve the same diagnostic accuracy and that all tests must be considered against a gold standard, hence this meta-analysis of literature aimed to synthesise the validity of each single diagnostic technique in identifying and staging laryngeal diseases. Methods: A systematic review of literature was led searching for articles mentioning the following terms including their various combinations to maximize the yield: larynx, laryngeal cancer, white light (WL) endoscopy, contact endoscopy (CE), stroboscopy, autofluorescence (AF), ultrasound (US), narrow band imaging (NBI), computers assail tomography (CAT), magnetic resonance imaging (MRI), positron emission tomography (PET). A quantitative analysis was carried on for paper published after 2005 onward, reporting a minumun series of 10 patients each study, declaring sensitivity and specificity of each diagnostic system. Results: The search identified 7215 publications, of which 3616 published after 2005, with a final results of a total of 214 articles stratified and included by our selection criteria. 58 out of 214 articles were selected for quantitative synthesis. 35 out of 58 studies had a quality score of ≥ 6 (good), 15 presented a score between 4 and 5 (fair), the remaining 8 had a score between 2 and 3 (poor). While objections can be raised about the pooling of different diagnostic procedures under the same group and the high level of heterogeneity in the meta-analyses, the inclusion of over 2500 patients makes the results fairly robust. Conclusions: A comprehensive overview of the most recent advances in laryngeal imaging technology combined with all of the information needed to interpret findings and successfully manage patients with voice disorders can be found herein. With these data, clinicians can risk-stratify patients and select proper examination modalities in order to provide appropriate care. Moreover, study limitations, together with possible clinical and research implications have been counted, as well