High-Risk HPV Testing in Head and Neck Carcinoma: Key Updates from the 2025 College of American Pathologists Guideline

Affiliations

¹ Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, WRN 219, Boston, MA, 02114, USA. Wfaquin@mgh.harvard.edu.
² Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
³ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁷ Office of the Director, The Joint Pathology Center, Silver Springs, MD, USA.
⁸ Department of Otolaryngology- Head and Neck Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁹ Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
¹⁰ Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

^# Contributed equally.

PMID: 41021082
PMCID: PMC12480157 (available on 2026-09-29)
DOI: 10.1007/s12105-025-01847-2

Review

High-Risk HPV Testing in Head and Neck Carcinoma: Key Updates from the 2025 College of American Pathologists Guideline

William C Faquin et al. Head Neck Pathol. 2025.

. 2025 Sep 29;19(1):115.

doi: 10.1007/s12105-025-01847-2.

Authors

Affiliations

¹ Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, WRN 219, Boston, MA, 02114, USA. Wfaquin@mgh.harvard.edu.
² Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
³ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁷ Office of the Director, The Joint Pathology Center, Silver Springs, MD, USA.
⁸ Department of Otolaryngology- Head and Neck Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁹ Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
¹⁰ Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

^# Contributed equally.

PMID: 41021082
PMCID: PMC12480157 (available on 2026-09-29)
DOI: 10.1007/s12105-025-01847-2

Abstract

High-risk human papillomavirus (HPV) plays a significant role in the pathogenesis of certain head and neck (HN) cancers, especially squamous cell carcinomas (SCC) arising in the oropharynx. Distinction between HPV-independent and HPV-associated HNSCC has important implications for clinical management and patient prognosis in specific anatomic subsites of the head and neck. In 2018, the College of American Pathologists (CAP) issued 14 evidence-based guideline statements related to the testing, application, interpretation, and reporting of HPV and surrogate marker testing for HN carcinomas. Since that time, significant amounts of new data have been published which serves as the foundation for the updated 2025 CAP Guideline resulting in 16 evidence-based recommendations. These statements refine issues related to the application of high-risk HPV testing in patients with HNSCC, and they address some issues not fully covered in the 2018 CAP Guideline. This brief review discusses the changes that were made to the original guideline and provides a quick reference for the testing recommendations across head and neck sites.

Keywords: HPV; Head and neck; Oropharynx; RNA ISH; Sinonasal carcinoma; Squamous cell carcinoma; Testing; p16.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflict of interest. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the authors, Department of Defense, or any component agency. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to Participate: For this type of study informed consent is not required. Consent for Publication: For this type of study consent for publication is not required.

References

1. Chaturvedi AK et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29(32):4294–4301 - PMC - PubMed
1. Marur S et al (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11(8):781–789 - PMC - PubMed
1. Khan A et al (2025) Evolution of testing for the diagnosis of human papillomavirus (HPV) status in head and neck squamous cell carcinoma: where from and where to? Oral Oncol 162:107208 - PubMed
1. Bonilla-Velez J et al (2013) Impact of human papillomavirus on oropharyngeal cancer biology and response to therapy: implications for treatment. Otolaryngol Clin North Am 46(4):521–543 - PMC - PubMed
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High-Risk HPV Testing in Head and Neck Carcinoma: Key Updates from the 2025 College of American Pathologists Guideline

Affiliations

High-Risk HPV Testing in Head and Neck Carcinoma: Key Updates from the 2025 College of American Pathologists Guideline

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous