Swab-based anal cancer screening in men living with HIV: Projected outcomes for different screening algorithms

Screening for and treatment of anal cancer precursor lesions, high-grade squamous intraepithelial lesions (HSIL), can prevent anal cancer. Recent guidelines set by the International Anal Neoplasia Society recommend digital anal rectal examination (DARE) and anal swab-based screening of high-risk individuals by means of high-risk (hr)HPV testing or cytology. We used our biobank containing data of more than 600 high-resolution anoscopy (HRA) screened participants (94% men with HIV) to compare the possible screening algorithms. We selected the 298 screening participants in whom anal swabs were successfully tested for hrHPV and cytology, parallel to HRA screening (DARE followed by complete visual inspection by HRA). We compared outcomes of several strategies (single-test, co-testing, two-step testing) with one or two positive tests required for HRA referral, resulting in 20 possible screening algorithms. We also assessed the sensitivity of DARE to detect anal cancer. We found that the percentage of missed HSIL was lowest with hrHPV testing, either alone (14.2%) or combined with cytology (≥ASCUS threshold: 4.4%; HSIL threshold: 8.8%) (co-testing or two-step testing, with ≥1 positive test required for HRA referral). Using these screening algorithms, 61.0 %, 79.0 %, and 63.7% of the participants were referred for HRA. While in some scenarios a small percentage of cancers was missed, all were detected by DARE. Whatever strategy is chosen, screening outcomes will have to be monitored closely to evaluate the program and make adaptations when necessary.