Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology.

Abstract

CONTEXT.—:

Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs).

OBJECTIVE.—:

To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—:

A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—:

Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (Ptrend ≤ .001) and within each HPV risk group (Ptrend ≤ .001 except for low-risk HPV [Ptrend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (Ptrend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001).

CONCLUSIONS.—:

p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

• Authors: Philip E Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E Torrez-Martinez, Salina M Torres, Mark H Stoler, Brigitte M Ronnett, Nancy E Joste, Teresa M Darragh, Patti E Gravitt, Mark Schiffman, William C Hunt, Walter K Kinney, Cosette M Wheeler, New Mexico HPV Pap Registry Steering Committee, p16 IHC Study Panel
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 144 Issue 6 Pg. 725-734 (06 2020) ISSN: 1543-2165 [Electronic] United States
• PMID: 31718233 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16

Topics

• Adult
• Biomarkers, Tumor (analysis)
• Cyclin-Dependent Kinase Inhibitor p16 (analysis)
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Papillomavirus Infections (complications)
• Uterine Cervical Neoplasms (classification, diagnosis, virology)
• Uterine Cervical Dysplasia (classification, diagnosis, virology)