목적: Since human papillomavirus (HPV) emerged as a new causal factor for oropharyngeal cancer, the rate of HPV related head and neck cancer has rapidly increased in Korea. Typically, HPV related head and neck cancer is diagnosed by p16 overexpression. Here, we analyzed the discordance between p16 positive head and neck cancer with HPV related head and neck cancer. 방법:From April 2022 to November 2023, as a result of searching for HPV related head and neck cancers diagnosed by PCR-based method, a total of 61 cases were collected. All cases were initially diagnosed by p16 immunohistochemistry, and followed by HPV genotyping to confirm HPV infection. 결과:Among 61 cases, 49 cases were diagnosed with oropharyngeal cancer (13 cases of BOT, and 36 cases of tonsil, 49 out of 61, 80.3%). Among 12 cases, 3 cases showed cancer unknown primary, 3 cases had oral cavity cancer, 2 cases had hypopharygeal cancer, and 4 cases showed other primary site. In 10 cases, HPV virus were not detected by PCR-based HPV genotyping. Among 10 cases, 4 cases were oropharyngeal cancer, 1 case was paranasal sinus cancer, 1 case was hypopharyngeal cancer, 3 cases were oral cavity cancer 1’ tongue. In oropharyngeal cancer, the positive rate of p16 immunohistochemistry method was 91.8% (45 out of 49). In other subsites, the positive rate of p16 immunohistochemistry method was 50.0% (6 out of 12). 결론: In oropharyngeal cancer, the diagnostic method using p16 immunohistochemistry showed 91.8% of accuracy in HPV related cancer, but in other subsites, the diagnostic methods using p16 showed an accuracy of 50%. According to our result, new diagnostic method for HPV-related cancer are needed to accurately diagnose HPV-related cancer.