The frequency of cervical lymph node carcinoma metastasis from unknown primary site(CCUP)has not decreased in spite of the improved capabilities of the tools needed for diagnosis. This has been reported as being related to the increasing incidence of HPV-related oropharyngeal cancer. In 2017, the 8th edition of the UICC was revised to require p 16 immunostaining and EBER for histological examination of the cervical lymph nodes in CCUP. In this study, we investigated the diagnosis of 27 cases of

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... CCUP that could not be determined by general examination. We performed p16 and TTF-1 immunochemistry, EBER in situ hybridization assay of the lymph nodes and compared the results with the clinical course. Of the 27 cases, the primary was found in 18 cases, including 1 case of nasopharyngeal carcinoma, 12 cases of oropharyngeal carcinoma, 4 cases of hypopharyngeal carcinoma, and 1 case of lung carcinoma. Positivity for EBER was found in the nasopharyngeal carcinoma case, and positive immunostaining for p16 was found in all cases of oropharyngeal carcinoma, confirming its reliability as a biomarker. In addition, the p16 positivity rate was 67% in 9 cases of unknown primary. Other authors have reported that about 80% of CCUP cases are p16-positive, suggesting the need for more careful observation of the lateral and anterior walls of the oropharynx when searching for the primary.