Surgeon-performed intraoperative transoral ultrasound improves the detection of human papillomavirus-positive head and neck cancers of unknown primary

Background: Squamous cell carcinomas of unknown primary (SCCUP) are often Human Papillomavirus (HPV)-positive. Due to their small size, extensive surgical workup is required to locate the primary tumors. High-frequency transoral ultrasound (US) may provide improved visualization of these small tumors. Our study aimed to explore whether surgeon-performed intraoperative transoral US for patients with HPV-positive SCCUP could improve primary tumor detection during panendoscopy. Methods: This was a single-center, prospective diagnostic study including patients undergoing panendoscopy under general anesthesia with HPV-positive SCCUP. Preoperative MRIs, PET/CTs, and HPV DNA-testing of lymph node metastases were performed in all patients. Intraoperative transoral US was performed prior to panendoscopy. Frozen section biopsies were performed unblinded to US results, and transoral US-guided biopsies were attempted if initial biopsies were negative. Final histopathology was obtained with palatine- and/or lingual tonsillectomy if frozen section was negative. The main outcome was the primary tumor detection rate with intraoperative transoral US and panendoscopy. Results: Thirty patients were included: 24 (80 %) were men, and the median age was 60 years [range 35-79 years]. Twenty-nine primary tumors (97 %) were confirmed; 18 (62 %) and 10 (34 %) in the lingual- and palatine tonsils, respectively, and one (3 %) in the posterior oropharynx. Transoral US had a significantly higher sensitivity than panendoscopy to locate the primary tumor (93 % vs 76 %, p = 0.02), and significantly higher than pre-operative PET/CT (62 %, p = 0.002), CT (45 %, p < 0.001), and MRI (28 %, p < 0.001). Conclusions: Intraoperative transoral US during panendoscopy is a promising diagnostic tool that may improve the detection of HPV-positive SCCUP.