Most anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer goes through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high-risk populations. We analyzed the inter-observer reproducibility of anal cytology in a population of 363 HIV-infected men who have sex with men (MSM). Liquid-based cytology (LBC) specimens were collected in the anal dysplasia clinic before performing high-resolution anoscopy (HRA) on all subjects. Papanicolaou-stained, LBC slides were evaluated by two cytopathologists, blinded to clinical outcome and the other pathologist's results, using the revised Bethesda terminology. Overall agreement between two observers was 66% (kappa 0.54, linear weighted kappa 0.69). Using dichotomizing cytology results (ASC-US or worse vs. less than ASC-US), the agreement increased to 86% (kappa 0.69). We observed an increasing likelihood of testing positive for markers associated with HPV-related transformation, p16/Ki-67 and HPV oncogene mRNA, with increasing severity of cytology results both for individual cytologists and for consensus cytology interpretation (ptrend < 0.0001 for all). In summary, we observed moderate to good agreement between two cytopathologists evaluating anal cytology samples collected in HIV-positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancers. Anal cytology may be used for anal cancer screening in high-risk populations, and biomarkers of HPV-related transformation can serve for quality control of anal cytology.
Keywords: anal cancer screening, cytology, human papillomavirus (HPV), human immunodeficiency virus (HIV), men who have sex with men (MSM), biomarkers