Anal Cytology Interpretation Issues: Observations from the College of American Pathologists’ Nongynecologic Cytology Program

Summary: Introduction: Anal cytology is important in the early detection of anal high-grade squamous intraepithelial lesion (HSIL) or worse. Though its histologic correlates are well studied, there is limited information regarding large scale interpretive issues. Here, we describe the recent performance of anal cytology in the College of American Pathologists' (CAP) Nongynecologic Cytology (NGC) Program. Materials and Methods: The CAP NGC Program anal cytology results were collated for the period 2015-2022. Invalid/inadequate responses were excluded. For each slide challenge thus included, concordance rates for the reference diagnoses (specific interpretations) and the general categories, i.e., ""negative"" (including those with organisms) and ""positive"" (≥low-grade squamous intraepithelial lesion [LSIL]), were derived. Mixed effect models were used to evaluate performance by preparation type (ThinPrep [TP]/SurePath [SP]), and participant type (pathologist/cytologist). All analyses were performed with SAS 9.4. Results: The final cohort comprised of 82,567 responses (laboratory/individual) from 807 slides. Overall, for the general categories, 82.8% of responses (10171/12281) were correctly classified as ""negative"" and 87.9% (60504/68837) as ""positive"". Of the reference diagnoses, LSIL was most frequently specifically interpreted (81.5%). Concordance rates for other reference diagnoses were: negative (73.7%), herpes simplex virus (HSV) (73.7%), amoeba (23.9%), HSIL (53.0%), squamous cell carcinoma (54.2%) (Figure 1). 32.0% of HSILs were interpreted as LSIL and 14.9% of HSV as ≥LSIL. Cytologists/Cytotechnologists were more likely to classify negative, LSIL, and HSV on TP, and negative on SP, in the correct general category compared to the pathologists (P<0.05). HSIL was more likely to be misclassified as negative on SP vs. on TP (P<.001). Conclusions: Though anal cytology is being increasingly utilized for anal cancer screening, our study highlights significant flaws in its interpretation across a large group of participants, and a need for additional education, particularly with regard to the findings of HSIL, HSV, and amoeba.