Decoding the Enigma: Harnessing HPV Testing for the Precision Care in Carcinoma Unknown Primary with Secondary Metastasis to the Neck in North Indian Population Undergoing TORS for Primary Identification

To assess the exact role of high-risk HPV testing in patients of carcinoma unknown primary with secondary metastasis to the neck who underwent TORS and neck dissection for identification of the primary site. A prospective study was carried out at a tertiary care centre over one year. Patients with unilateral neck swelling, which was cytologically proven squamous cell carcinoma neck metastasis, were included in the study. After clinicopathological evaluation, they underwent TORS-assisted ipsilateral radical tonsillectomy, tongue base mucosal wedge biopsy for primary site identification, and ipsilateral neck dissection. They underwent HPV RNA ISH from the tonsil, the base of the tongue and blood. They also underwent HPV DNA testing from the blood. P16 was done in the base of tongue, tonsil, and lymph node specimens . In the study cohort of 18 patients who underwent ipsilateral radical tonsillectomy, mucosal tongue base wedge biopsy and neck dissection, p16 positivity was isolated in 5.56%, 0% and 2.78% of patients, respectively. (n = 1/18, 0/18, 5/18). Interestingly, HPV E7 mRNA expression was absent in the tonsil /base of tongue specimens, but metastatic lymph nodes displayed expression in 11.11%. HPV DNA was undetected in all analysed tissues and patients’ blood. In the Indian subcontinent, it is not essential to do detailed high-risk HPV analysis in cases of carcinoma unknown primary with secondary metastasis to the neck.