Evaluating the Performance of Anal Cytology and Human Papillomavirus Testing for Detection of Anal Cancer and Pre-Cancerous Lesions.

BACKGROUND Anal squamous cell carcinoma (SCC) incidence is rising; however, anal cancer screening guidelines require further refinement. This study evaluated the accuracy of anal cytology and human papilloma virus (HPV) testing for anal cancer screening in our pathology service, identifying limitations of these tests when applied to this role.

METHODS Pathology records of all 240 patients who had undergone anal or perianal biopsy during 2023 were evaluated. Reports for 1364 smears, 817 biopsy procedures, and 1441 HPV tests conducted on these patients between 2002 and 2024 were reviewed.

RESULTS The cohort included 413 biopsy diagnoses of high-grade squamous intraepithelial lesion (HSIL) and 8 of anal SCC. Using 406 smears conducted on the same day as biopsy, cytology demonstrated a high sensitivity (86.3%) but poor specificity (31.9%) for identification of high-grade lesions if a cytological diagnosis of possible low-grade SIL (pLSIL) or worse was the criterion to proceed to biopsy (International Anal Neoplasia Society (IANS) guidelines). Specific examination of limitations of cytology included poorer detection of anal intraepithelial neoplasia 2 (AIN2) and AIN2/3 lesions (p < 0.001), where surface epithelial maturation and keratinisation may obscure sampling of dysplastic cells. Of 6 patients diagnosed with high-grade lesions but testing negative for high-risk HPV, re-testing using the paraffin-embedded biopsy tissue detected HPV16 in 4.

CONCLUSIONS Anal cytology and HPV testing perform important and complementary roles in the context of anal cancer screening, but each is associated with technical limitations. While the sensitivity of testing is excellent, improvements in specificity are required to prevent unnecessary biopsy.