HER2/neu in head and neck cancers: A worthy target or not?
Authors: Rohatgi Nitesh , Sharma Kunal , Garg Nidhi , Kembhavi Priyanka , Karanth Suman , Pais Anurita , Manudhane Roopali , Bahl Ankur 
Published: June 2024

e18022 Background: Head and neck cancers (HNC) account for a major public health problem across the globe, more so in India where it ranks as the second most common cancer. Most cases involve oral cavity due to use of chewable tobacco products and more than 65% present in locally advanced stage. It thus becomes imperative to continuously look for newer, more advanced targets and treatment modalities. One such target we sought to evaluate was HER2/neu, which has been successfully used for treatment in different tumors showing HER2/neu amplification from breast cancers to Gastric cancers and others, significantly improving survival outcomes. Further, with the development of Trastuzumab Deruxtecan now being evaluated as a tumor agnostic antibody for cancers showing even low levels of HER2/neu expression, we attempted to assess the incidence of HER2/neu expression (including HER2 low) in 50 cases of HNC using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) with an aim to evaluate the utility vs futility, of treatment with Anti-HER2 antibody. Methods: Retrospective analysis was done in 50 recent cases of HNC diagnosed at Global Reference Laboratory, Agilus Diagnostics and they were evaluated for HER2/neu expression by IHC using the FDA approved Ventana clone. The study design was akin in most aspects to HER2/neu analysis in breast cancer, in which, on IHC, Score 3+ was considered positive and Score 0 was considered negative, both of which not warranting subsequent FISH analysis. Score 2+ on IHC was considered equivocal and thus subjected to FISH for confirmation. Positive cases in this category would be considered positive while negative cases would be considered negative but analyzed for appropriate group and kept in a separate category of HER2/neu low for analysis and future reference. Score 1+ though considered negative was also subjected to FISH to analyze copy numbers and HER2/CEP17 ratio and these cases were also clubbed separately in HER2/neu low group for analysis and future reference. Results: In 50 cases analyzed, none tested positive (Score 3+) for HER2/neu on IHC. Two cases showed equivocal staining while six cases showed Score 1+. Both equivocal cases tested negative on FISH and fell in Group 5 as per the latest 2023 guideline update. Of the six cases which showed Score 1+ on IHC, four cases fell in Group 5 while two showed Group 4 pattern. Thus, none of the cases were positive for HER2/neu as per the recent guidelines, while 8 cases fell under the category of HER2/neu low expression by definition. Conclusions: This study is in concordance with extremely low HER2 expression documented in HNC implying the futility of treatment with current Anti- HER2 antibodies. However, 16% cases showing HER2/neu low expression definitely make it prudent to do clinical studies assessing the utility of Trastuzumab Deruxtecan and similar antibody drug conjugates in this setting just like other tumor types where numerous studies are already undergoing at the moment.