Janira Navarro highlights p16 pitfall

Pathologist Janira Navarro used a teaching case to argue that a p16-positive cervical squamous lesion should still be graded by morphology first, not by stain alone. (cap.org) (x.com) p16 is an immunohistochemistry stain, a lab dye that lights up a cell-cycle protein often overexpressed in human papillomavirus-driven lesions. In cervical pathology, strong diffuse “block-positive” staining can support a diagnosis of high-grade squamous intraepithelial lesion. (pathologyoutlines.com) (cap.org) But the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology say p16 is an adjunct for specific biopsy dilemmas, not a replacement for what the hematoxylin-and-eosin slide shows. Their 2025 update says pathologists should use p16 when the morphologic differential is between high-grade squamous intraepithelial lesion and a mimic. (cap.org 1) (cap.org 2) That distinction matters because low-grade and high-grade lesions are different categories with different management implications. Cervical intraepithelial neoplasia 1 corresponds to low-grade squamous intraepithelial lesion, while cervical intraepithelial neoplasia 2 and 3 fall under high-grade squamous intraepithelial lesion. (mypathologyreport.ca) (cap.org) The CAP-ASCCP guidance is explicit on the pitfall Navarro was highlighting: any p16-positive area must still meet hematoxylin-and-eosin morphologic criteria before it is reinterpreted as high grade. The same guidance says routine p16 is not recommended when a biopsy already reads clearly as negative, cervical intraepithelial neoplasia 1, or cervical intraepithelial neoplasia 3. (pathologyoutlines.com) (cap.org) Cytology uses a different reporting framework from tissue biopsy. The Bethesda System standardizes Pap test reporting for cervical cytology, while LAST standardizes histopathology terminology for human papillomavirus-associated lower anogenital lesions. (pmc.ncbi.nlm.nih.gov) (cap.org) ASCCP’s current biomarker guidance for screening does recognize p16 in a different form — p16/Ki-67 dual-stain cytology — as a triage test after positive human papillomavirus results. That is not the same as using single-marker p16 immunohistochemistry to upgrade a Pap interpretation or to bypass morphology on tissue. (asccp.org) (diagnostics.roche.com) Navarro’s case reportedly ended with excision showing high-grade squamous intraepithelial lesion, cervical intraepithelial neoplasia 2. Her teaching point tracked the guideline language: p16 can support a call, but the slide’s architecture and maturation pattern still drive the grade. (x.com) (cap.org) The takeaway from the case is narrow and practical. A positive p16 result can sharpen an equivocal biopsy, but it does not turn low-grade morphology into high-grade disease by itself. (cap.org) (pathologyoutlines.com)