Classifying Anal Intraepithelial Neoplasia 2 Based on LAST Recommendations

Yuxin Liu, W. Glenn McCluggage, Teresa M. Darragh, Wenxin Zheng, Jennifer M. Roberts, Kay J. Park, Pei Hui, Morgan Blakely, Keith Sigel, Michael M. Gaisa

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Objectives: The Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus-Associated squamous lesions into low-and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories. Methods: Agreement based on photomicrographs of HandE alone or HandE plus p16 immunohistochemistry was calculated using ? coefficients. Results: Agreement was fair based on HandE alone (? = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (? = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (? = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 HandE diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs. Conclusions: Although p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment.

Original languageEnglish (US)
Pages (from-to)845-852
Number of pages8
JournalAmerican journal of clinical pathology
Issue number6
StatePublished - Jun 1 2021


  • Anal intraepithelial neoplasia 2
  • Human papillomavirus
  • Interobserver agreement
  • p16 Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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