TY - JOUR
T1 - Relationships of p16 immunohistochemistry and other biomarkers with diagnoses of cervical abnormalities implications for LAST terminology
AU - Castle, Philip E.
AU - Adcock, Rachael
AU - Cuzick, Jack
AU - Wentzensen, Nicolas
AU - Torrez-Martinez, Norah E.
AU - Torres, Salina M.
AU - Stoler, Mark H.
AU - Ronnett, Brigitte M.
AU - Joste, Nancy E.
AU - Darragh, Teresa M.
AU - Gravitt, Patti E.
AU - Schiffman, Mark
AU - Hunt, William C.
AU - Kinney, Walter K.
AU - Wheeler, Cosette M.
N1 - Funding Information:
Information reported in this publication was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health under award number U19AI113187 and through its Developmental Research Pilot (DRP) program. Roche Molecular Systems and Ventana, a Roche Company, provided reagents and equipment at no cost.
Publisher Copyright:
© 2020 College of American Pathologists. All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - Context.-Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4aimmunohistochemistry (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.
AB - Context.-Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4aimmunohistochemistry (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.
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U2 - 10.5858/arpa.2019-0241-OA
DO - 10.5858/arpa.2019-0241-OA
M3 - Article
C2 - 31718233
AN - SCOPUS:85083190427
SN - 0003-9985
VL - 144
SP - 725
EP - 734
JO - Archives of Pathology and Laboratory Medicine
JF - Archives of Pathology and Laboratory Medicine
IS - 6
ER -
