The Accuracy of Anal Swab-Based Tests to Detect High-Grade Anal Intraepithelial Neoplasia in HIV-Infected Patients: A Systematic Review and Meta-analysis

Background. The incidence of high-risk human papillomavirus (HR-HPV)-induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab-based tests to detect AIN in HIV-positive patients. Methods. We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results. We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%-87%) and specificity of 45% (95% CI, 44%-66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%-67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%-95%) and the specificity was 27% (95% CI, 21%-33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%-50%) and the negative predictive value (NPV) was 87% (95% CI, 78%-93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%-73%) and an NPV of 78% (95% CI, 65%-87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%-57%) and the NPV was 87% (95% CI, 79%-93%). Conclusions. Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.