PAP-HPV Co-Testing in Anal Cancer Screening: An Italian Experience

<b>Background/Objectives</b>: Squamous cell carcinoma of the anus (SCCA) remains a relatively rare form of cancer linked to high-risk human papillomavirus (HR-HPV) infection; however, its incidence has been increasing globally. Anal cytology and HR-HPV testing can identify precursors, though standardized screening guidelines are still lacking. This study aimed to assess the correlation between high-resolution anoscopy (HRA) findings and primary screening results through PAP-HPV co-testing in high-risk patients. <b>Methods</b>: A retrospective, single-center study was conducted collecting data from the joint multidisciplinary anal cancer clinic of Piero Palagi Hospital in Florence (Italy), between August 2019 and September 2022. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of anal cytology, HR-HPV testing, and PAP-HPV co-testing were assessed. <b>Results</b>: In 577 HRAs, histology revealed 31 AIN2+ lesions (5.4%) and 220 AIN1 lesions (38.1%), while 326 (56.5%) were negative. Cytology alone showed a sensitivity of 74.2% and specificity of 63.3% for AIN2+ lesions, while HR-HPV testing alone had a sensitivity of 96.8% and specificity of 38.1%. Co-testing demonstrated 100% sensitivity and a 100% NPV for AIN2+ lesions. Among men who have sex with men (MSM), no significant differences in outcomes were observed between HIV-positive and HIV-negative patients, likely reflecting similar high-risk behaviors and effective HIV treatments. <b>Conclusions</b>: Co-testing with anal cytology and HR-HPV testing provides the most reliable screening for high-grade lesions (AIN2+), surpassing the reliability of individual methods. Tailored co-testing strategies are crucial for early detection and effective prevention in high-risk groups.