Providers and even patients may question why p16 appears so frequently on reports (and bills) when it comes to cervical/endocervical biopsies. The use of p16 in cervical biopsies improves the accuracy of cervical intraepithelial neoplasia (CIN) diagnosis and grading and decreases its interpathologist variability. A surrogate marker of high-risk HPV, p16 has the ability to help discriminate and identify subtle dysplasias/malignancies in often fragmented, miniscule cervical biopsy specimens. This immunohistochemical (IHC) stain has been an invaluable tool for pathologists over many years.


More recently, however, the use of p16 has been incorporated into Gynecologic society recommendations due to the vast amount of literature that describes how its use improves patient care. The LAST (Lower Anogenital Squamous Terminology) project showed how p16 can often identify high-grade dysplasia which would otherwise be missed, and both prevent overall and undercall of high grade dysplasias. Consequently, the LAST project issued a list of recommendations, describing how to use p16.


The ASCCP Risk-Based Management Consensus Guidelines were also recently updated in 2019 to reflect this, noting the following:


“It is important to use p16 immunohistochemical (IHC) staining according to the guidance provided by the CAP-ASCCP LAST Project. p16 IHC should be used for specific indications as recommended by LAST when interpreting the H&E slide.”


These specific indications include:


  • Any time the differential diagnosis includes HSIL/CIN 2.
  • Any time the current biopsy is LSIL/CIN 1 or Negative, and the previous Pap cytology showed HSIL, ASC-H, AGUS or ASCUS (type 16 HPV positive.)


At PathAdvantage, where gynecologic pathology and women’s health are our specialty, we are highly experienced in how and when to use p16 judiciously in evaluating patient biopsies.