High TROP2 expression is frequent and linked to nodal metastasis in head and neck cancer

Head and neck cancers constitute a highly heterogeneous group of malignancies exhibiting variable clinical outcomes. Despite advances in surgery, radiotherapy, and systemic treatments, more than 300,000 patients worldwide die annually from these cancers. The identification of novel molecular markers to improve patient stratification and to guide personalized treatment approaches is therefore urgently needed. The membrane glycoprotein Trophoblast cell surface antigen 2 (TROP2) is the molecular target of sacituzumab govitecan (SG), an antibody-drug conjugate that has been approved for the treatment of metastatic triple-negative breast cancer and advanced urothelial carcinomas. Additionally, it has shown promising clinical activity in other tumor types, such as non-small cell lung cancer, and gastrointestinal cancers. To evaluate the prevalence and potential clinical significance of TROP2 expression in head and neck cancer, we analyzed a total of 583 head and neck cancers by immunohistochemistry (IHC) in a tissue microarray format. H score analysis was used to define cancers as strongly positive (h-score 300), moderately positive (200-299), weakly positive (1-199), or negative (0). TROP2 expression was found to be strong in 53.7%, moderate in 18.8%, weak in 22.8%, and negative in 4.7% of 531 evaluable head and neck carcinomas. There was a marked variability of TROP2 expression between tumors of different localization. TROP2 expression was found to be strong in 61.2% of 336 carcinomas of the oropharynx, 48.0% of 25 cancers of the hypopharynx, 40.1% of 143 cancers of the larynx, 37.5% of 8 carcinomas of the oral cavity, and in 21.4% of 14 carcinomas of the nasopharynx (p=0.0028). Among 347 patients with data on the pN-stage, high TROP2 expression was associated with nodal metastasis (p=0.0002). However, the level of TROP2 expression was statistically unrelated to pT-stage (p=0.3206), histologic grade of malignancy (p=0.7732), presence of distant metastasis (M1, p=0.4024), L-status (p=0.2895), and V-status (p=0.6822). It is concluded from our data, that high level TROP2 expression is very common in head and neck cancers. Accordingly, many patients with these tumors could potentially benefit from SG treatment. Site specific differences in TROP2 expression levels are likely to be driven by location-specific risk factors for subtypes of head and neck cancers.