Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists

TLDR

Human papillomavirus is a major cause of oropharyngeal squamous cell carcinoma and its status is a prognostic marker, yet no consensus exists on when or how to test for HPV/p16. The study aims to develop evidence‑based recommendations for testing, interpreting, and reporting HPV and surrogate marker tests in head and neck carcinomas. An expert panel performed a systematic literature review and, using evidence strength, feedback, and consensus, formulated the recommendations. The guidelines recommend testing all newly diagnosed oropharyngeal SCC patients for high‑risk HPV with p16 immunohistochemistry at a 70 % cutoff, reporting tumors as HPV or p16 positive, and advise against routine testing of nonsquamous or nonoropharyngeal carcinomas, with additional guidance for cytology and recurrence specimens.

Abstract

Context Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinomas, and HPV (and/or surrogate marker p16) status has emerged as a prognostic marker that significantly impacts clinical management. There is no current consensus on when to test oropharyngeal squamous cell carcinomas for HPV/p16 or on which tests to choose. Objective To develop evidence-based recommendations for the testing, application, interpretation, and reporting of HPV and surrogate marker tests in head and neck carcinomas. Design The College of American Pathologists convened a panel of experts in head and neck and molecular pathology, as well as surgical, medical, and radiation oncology, to develop recommendations. A systematic review of the literature was conducted to address 6 key questions. Final recommendations were derived from strength of evidence, open comment period feedback, and expert panel consensus. Results The major recommendations include (1) testing newly diagnosed oropharyngeal squamous cell carcinoma patients for high-risk HPV, either from the primary tumor or from cervical nodal metastases, using p16 immunohistochemistry with a 70% nuclear and cytoplasmic staining cutoff, and (2) not routinely testing nonsquamous oropharyngeal carcinomas or nonoropharyngeal carcinomas for HPV. Pathologists are to report tumors as HPV positive or p16 positive. Guidelines are provided for testing cytologic samples and handling of locoregional and distant recurrence specimens. Conclusions Based on the systematic review and on expert panel consensus, high-risk HPV testing is recommended for all new oropharyngeal squamous cell carcinoma patients, but not routinely recommended for other head and neck carcinomas.