The impact of histopathology on prognosis of squamous cell carcinoma of the larynx: can we do better?

Despite decades of progress, laryngeal squamous cell carcinoma (SCC) is still associated with significant morbidity and mortality worldwide. Additional biomarkers are needed to apply precision medicine and predict the clinical course. We reviewed and summarised routinely reported histopathologic features (e.g. subtypes of laryngeal SCC) along with promising potential biomarkers not yet routinely assessed using international guidelines. These include extra- vs intratumoural vascular and perineural invasion, tumour budding, depth of invasion, and tumour-infiltrating lymphocytes. We also address the problem of specimen quality and type (open approach vs endoscopic surgery) and the related limitations. High-risk human papillomavirus infection is another controversial issue to be discussed, being rare in laryngeal SCC, with an indeterminate prognostic significance and less reliable p16 overexpression as a surrogate marker of HPV infection. Further studies are warranted to address the applicability and to see which of the described parameters may help to better stratify patients with laryngeal SCC and should therefore be included in the pathology report.