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

Abstract

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.

Human Papillomavirus Detection and Abnormal Anal Cytology in HIV-infected Patients Using p16/Ki-67 Dual-Staining

“…HPV has a particularly high prevalence among HIV-infected patients. HPV DNA testing is recommended an alternative or an adjunct to cytology (Dias et al, 2019). In our anal samples collected for modified LBC, the prevalence of HPV infection was 34.14%, which lies within the range noted in previous publications (Gandra et al, 2015;Stier et al, 2015).…”

Recommendations Favoring Anal Cytology as a Method for Anal Cancer Screening: A Systematic Review

“…Several studies have shown that the sensitivity of anal cytology is similar to that of cervical cytology [13,14], although with a lower specificity [26]. A recent systematic review and meta-analysis described the performance of anal cytology (any abnormality as a threshold) to detect HSIL, in HIV-positive, with a sensitivity of 82% (95% Confidence Interval (CI), 74-87%) and specificity of 45% (95% CI, 44-66%), with a total of 18 studies included [27]. In a study by Albuquerque et al [14], including 636 anal cytology samples and 323 biopsies, the sensitivity of anal cytology (any abnormality as the threshold) for predicting histological HSIL/cancer was 92% (95% CI, 78-97%) and the specificity 60% (95% CI, 48-71%), in immunosuppressed women with a history of anogenital tract neoplasia.…”

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

“…Studies are needed to inform guidelines to recommend screening, such as the Anal Cancer/HSIL Outcomes Research (ANCHOR) Study, which is designed to determine if screening for and treating anal HSILs is effective in reducing the incidence of anal cancer. Similar to other, older populations [ 20 ], anal cytology in young MSMLWH had limited sensitivity for the detection of HSILs ( Supplementary Table 1 ), unless the threshold for screening included Atypical squamous cells of undetermined significance (ASC-US), and anal cytology underestimated the level of disease detected.…”