The College of American Pathologists (CAP) has released its 2026 Q1 update to the CAP Cancer Protocols, introducing major revisions aimed at improving consistency, clarity, and alignment with current oncologic classification standards.
CAP has also published a new article addressing why commonly used mismatch repair and microsatellite instability testing methods may yield different—but still valid—results.
Clinical laboratories rely on CAP Cancer Protocols to standardize tumor reporting and align with widely used frameworks including WHO classification, AJCC staging, and accreditation requirements.
Head and neck cancer reporting redesigned
A major focus of the latest update is a restructuring of head and neck cancer protocols. CAP has retired the broader Pharynx and Major Salivary Gland protocols, replacing them with more site-specific frameworks, including HPV-associated and HPV-independent oropharynx protocols, hypopharynx, nasopharynx, salivary gland, and mucosal melanoma.
The update also introduces implementation of AJCC Version 9 staging for select head and neck protocols, including HPV-associated oropharynx, nasopharynx, and salivary gland cancers.
Reporting refinements include expanded lymph node data requirements, addition of tumor bed margin status, and updates to biomarker-related fields. Several elements previously considered conditional are now required core reporting components in select protocols.
Biomarker sections were also revised, with updates to HPV and HER2-related content, refined HER2 scoring criteria, and terminology changes reflecting WHO 5th edition classifications, including SWI/SNF complex–deficient sinonasal carcinoma.
Overall, the 2026 Q1 release revises 11 protocols and retires two legacy protocols, with some updates affecting laboratory accreditation timelines.
MMR/MSI testing differences
Testing for MMR deficiency and MSI involves three main approaches: immunohistochemistry (IHC), polymerase chain reaction (PCR)-based assays, and next-generation sequencing (NGS). IHC evaluates MMR protein expression, while PCR-based MSI assays and NGS panels assess DNA-level instability; NGS can also detect mutations in MMR genes.
In a new Precision Medicine article from the CAP, co-authors Matthew Hiemenz, MD, FCAP, and Jeremy Ward, MD, PhD, FCAP, explain how these commonly used methods can produce discordant findings and offer guidance for interpreting conflicting results in clinical practice.
The reason: these tests measure different aspects of tumor biology. Because IHC evaluates protein expression and molecular assays assess genomic instability, each method may detect abnormalities that others miss.
Rather than signaling an error, discordant results can reflect biological complexity and differences in assay sensitivity.
“For years, we treated these tests as interchangeable, but they measure different biology. IHC evaluates protein expression, while PCR and NGS assesses functional instability at the DNA level. Discordance is not always an error, sometimes it’s a reflection of the tumor biology itself,” said Jeremy Ward, MD, PhD, FCAP, in a CAP video accompanying the article.
“The future isn’t about picking the one best test—it’s about using integrated tumor-specific algorithms to guide immunotherapy.”
Together, these updates reflect ongoing shifts toward more standardized cancer reporting and more integrated interpretation of molecular testing in clinical decision-making.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
