The College of American Pathologists recently updated its evidence-based guideline recommendations for the testing of human papillomavirus in head and neck carcinomas.
Guideline co-chairs William Faquin, MD, PhD, a pathologist at Boston-based Massachusetts General Hospital, and James Lewis Jr., MD, a pathologist at Phoenix-based Mayo Clinic in Arizona, shared with Becker’s what this update means for HPV testing in the clinical setting.
Editor’s note: Responses have been lightly edited for clarity and length.
Question: What prompted this guideline update?
Dr. William Faquin: HPV-associated squamous cell carcinoma continues to be a major cause of carcinomas involving the head and neck. The 2025 update to the 2018 CAP guideline aims to enhance and standardize HPV testing across pathology practice settings by capturing new research and emerging technologies to improve diagnostic accuracy.
Since the original CAP guideline was originally published, it has become clear that, in some circumstances, HPV-specific testing should play a greater role in the testing algorithm. In addition, HPV testing guidelines are needed for sinonasal squamous cell carcinomas where HPV has been identified to play an etiologic role in a subset of these cancers.
Q: How do you envision the guideline’s expanded recommendations to influence clinical care and/or treatment approaches for head and neck cancers?
Dr. James Lewis: The new approach to still centering around p16 immunohistochemistry as the “across the board” test for classification. However, we are trying to be more cautious – in a word, trying to “fence it in.”
If people consistently apply these recommendations, we expect the rate of patients with discrepant results between p16 immunohistochemistry and HPV-specific testing to decrease, which should result in more consistent patient classification and better clinical outcomes overall.
The expansion of the use of HPV-specific testing on cytology specimens — over p16 alone or no testing at all — should help decrease the rate of nondiagnostic cervical lymph nodes by fine-needle aspiration cytology, and should decrease the amount of additional tissue biopsies that are taken just to ascertain the patient p16/HPV status.
Finally, the recommendation for routine p16/HPV testing for patients with sinonasal squamous cell carcinoma should help radiation and medical oncologists, as well as surgeons, to more appropriately treat these patients knowing they respond better to the treatment and generally have better survival.
Q: What are the main challenges to standardizing testing practices? How can those challenges be overcome?
WF: Probably the greatest challenge in both the U.S. and globally is educating pathologists about the updated guideline for HPV testing in the head and neck. The updated guideline consists of 16 guideline statements, and there are important details that need to be followed in order for pathologists to provide the best standardized results. These results can influence how a patient’s head and neck squamous cell carcinoma will be managed, including patient eligibility for clinical trials.
In addition to the main guideline publication in Archives of Pathology & Laboratory Medicine, details about the updated CAP guideline will be addressed in multiple shorter commentary-style articles to be published in subspecialty journals as well as in presentations at various national and international pathology-related meetings over the next two years.
Q: Looking ahead, what emerging trends or technologies in HPV testing should labs/healthcare organizations be preparing for now?
JL: Clearly the “elephant in the room” is circulating HPV DNA detection. With high sensitivity and very high specificity, the detection of high-risk HPV DNA in the blood is highly correlated with the HPV status in the patient’s tumor tissue. It can also be used for treatment follow-up and detection of recurrent disease. In addition, people are weighing its possible utility as a screening test for healthy patients before they even have signs of cancer.
Although we did not cover circulating HPV DNA testing in the guideline update, we did talk about it, and fully expect that it will have a huge impact on any future revised guidelines.
Regarding tissue-based testing, the functionality and availability of high-risk HPVRNA in situ hybridization looms large. As it becomes more and more available, it may potentially emerge as a single tissue-based HPV test for all oropharyngeal and sinonasal squamous cell carcinoma patients. Further research and development to make these tests available on our commonly available analyzers and across practices will be critical.
