Abstract Introduction/Objective HPV-positive oropharyngeal squamous cell carcinoma is biologically and clinically unique and has a survival advantage over other head and neck squamous cell carcinomas. In December 2017 College of American Pathologist published guidelines for testing HPV status in head and neck cancer. It was recommended that pathologists perform HR-HPV testing on head and neck squamous cell carcinomas from all patients with known oropharyngeal SCC not previously tested for HR-HPV, with suspected oropharyngeal SCC, or with metastatic SCC of unknown primary. The aim of this study was to determine the compliance of pathologists following the CAP guidelines. Methods Cases that underwent HPV testing using p16 immunohistochemistry for the years 2017 and 2019 were retrieved. Based on the guidelines, p16 testing was designated as “indicated” or “not indicated”. Results There were 196 cases in which p16 testing was performed in a period of 3 consecutive years. Of these, 175 were FNA/ biopsies and 21 were surgical resections. In 69 cases (56 FNAs and 13 biopsies) the biopsy was performed on neck masses with unknown primary. The compliance for p16 testing in OPC and Lymph nodes with metastatic SCC of unknown primary was 100%. In 34 (17.3%) cases p16 testing was not indicated, the most common reason being wrong site (85%) including the larynx, oral tongue, the floor of the mouth, buccal mucosa, and nasal mass. Of the unindicated p16s, 20 (58%) were received in consultation for continuity of care. Conclusion Not being clear about the site of the tumor is the most common reason for unindicated p16 testing. A clear designation of biopsy site and proper communication between pathologist and surgeon can improve utilization of p16 testing in head and neck carcinomas.