Anal Dysplasia: A Review of Pathology with Focus on Current Terminology, Pathologic Diagnosis, and Diagnostic Challenges

Abstract

Anal cancer, although rare, has been increasing in incidence, particularly among high-risk groups such as individuals with human immunodeficiency virus (HIV) and men who have sex with men. The majority of anal cancers are squamous cell carcinomas, most of which are associated with high-risk human papillomavirus (HPV), particularly HPV16. The diagnosis of anal dysplasia requires a multifaceted approach involving clinical evaluation, cytology, high-resolution anoscopy, and histopathologic examination. This review highlights the current understanding of the pathogenesis, diagnostic challenges, and management of HPV-related anal dysplasia and cancer. The evolution of diagnostic terminology, notably the adoption of the two-tiered classification system for HPV-related anal squamous lesions, has improved the consistency of diagnosis. Early detection of anal dysplasia is crucial for effective treatment, particularly in high-risk populations. While anal cytology is a key screening tool, its low specificity necessitates confirmatory diagnosis through anal biopsy with the aid of ancillary tests, including p16 and K_i-67 staining, and HPV DNA/RNA testing. However, challenges still remain, such as interobserver variability and the potential for false positives or false negatives, highlighting the need for standardized reporting and multidisciplinary collaboration.

Keywords

anal - dysplasia - cytology - LSIL - HSIL - p16 - Ki67 - ISH - interobserver reproducibility

Publication History

Article published online:
17 June 2025

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