Abstract
BACKGROUND: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA). METHODS: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing. Three screening procedures were compared with aLBC: biomarker alone, cytology and biomarker in all, and cytology and reflex biomarkers (biomarkers applied if aLBC results were atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion). Biomarkers included Linear Array (LA), LA for 14 high-risk human papillomavirus (LA 14 HR-HPV) genotypes, LA HPV-16, Hybrid Capture 2 (HC2), E6/E7 mRNA, and E6/E7 mRNA HPV-16. RESULTS: Of 354 participants, 179 (50.6%) had atypical squamous cells of undetermined significance or worse, requiring HRA (sensitivity, 80%; specificity, 57.3%; area under the curve, 0.687; reference, biopsy-proven HSIL). Cytology and reflex biomarkers per E6/E7 mRNA, LA 14 HR-HPV, and HC2 and the biomarker-alone procedure with HC2 showed comparable accuracy (sensitivities: 71.6%, 78.8%, 73.1%, 75.7%; specificities: 73.5%, 67.9%, 76.1%, 65.5%; areas under the curve: 0.726, 0.734, 0.746, 0.706) with fewer HRA referrals (number needed to diagnose: 2.2, 2.1, 2, 2.4). CONCLUSIONS: Our findings suggest that E6/E7 mRNA, LA 14 HR-HPV, and HC2 in the cytology and reflex biomarkers procedure, as well as HC2 in the biomarker-alone procedure, can improve anal HSIL screening effectiveness.