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 - 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 -