p16 immunostaining in cytology specimens: its application, expression, interpretation, and challenges

Area of Science:

• Oncology
• Pathology
• Cytopathology

Background:

• p16 immunostaining is a surrogate marker for HPV-related head and neck squamous cell carcinomas (HNSCC).
• The diagnostic utility of p16 in cytology specimens requires further evaluation.

Purpose of the Study:

• To assess the utility of p16 immunostaining in cytology specimens for diagnosing HPV-related carcinomas.
• To correlate p16 staining intensity with HPV status across various body sites and sexes.

Main Methods:

• Retrospective search of cytology cases with p16 immunostaining (2014-2018).
• Categorization of cases by body site and quantification of p16 staining intensity (negative, focal/patchy, diffuse).
• Correlation of p16 results with HPV testing where available.

Main Results:

• 372 cases were analyzed; head/neck cases showed significant sex-based differences in p16 application.
• Diffuse p16 staining was observed in squamous cell carcinomas, small cell carcinomas, and gynecologic serous carcinomas.
• HPV correlation showed strong association with diffuse p16 (127/138 HPV+), but not with focal/patchy staining (6/20 HPV+).

Conclusions:

• Diffuse p16 staining is valuable for diagnosing HPV-related carcinomas, especially HNSCC, across different body sites and sexes.
• Focal/patchy p16 staining lacks correlation with HPV status.
• Accurate diagnosis requires correlating p16 intensity with cytomorphology, clinical history, and ancillary studies like p40 immunostaining.