Diagnostic utility of high-risk human papillomavirus mRNA in situ hybridisation in squamous cell carcinoma of unknown primary in the head and neck and implementing American Society of Clinical Oncology guideline recommendations.

HPV-RNA ISH is a robust and reliable method for detecting HPV-related HNSCC on cytology material showing concordance rate of 92.3% between HPV-RNA ISH and P16, which is a sensitive but non-specific marker. Compared to HPV-DNA ISH, HPV-RNA ISH reproducibly identifies HPV-related HNSCC with fewer discrepancies between cytology and histology. The findings of this study are in agreement with the ASCO recommendations.