International Journal of Medical Microbiology · Oct 22, 2026

Human papillomavirus oncogene mRNA testing for anal dysplasia and anal cancer screening in men living with HIV

By Silling S, Kreuter A, Potthoff A et al.

BACKGROUND: Anal human papillomavirus (HPV)-induced high-grade squamous intraepithelial lesions (HSIL) are very frequent in men who have sex with men living with HIV (MSMLWH). Anal cancer screening is recommended for MSMLWH. This study aimed to evaluate the diagnostic accuracy of high-risk (hr)-HPV oncogene-mRNA testing for the detection of HSIL/anal cancer (HSIL+) in MSMLWH. METHODS: 3204 intraanal swabs were collected from 865 MSMLWH participating in an anal cancer screening programme including anal cytology/histology, high-resolution anoscopy, and HPV-DNA-typing between 2010 and 2023. Hr-HPV-mRNA and hr-HPV-DNA analyses were performed on 865 baseline swabs. HSIL-free survival up to 96 months was estimated stratified by hr-HPV-mRNA status at baseline. RESULTS: For the detection of HSIL+, sensitivity, negative predictive value, and positive predictive value were similar for hr-HPV-mRNA (92.4%, 95.3%, 26.9%) and hr-HPV-DNA testing (88.9%, 90.7% 23.0%). Specificity was significantly higher for hr-HPV-mRNA (38.0%, 95%CI 34.4-41.8) compared to hr-HPV-DNA (26.7%, 95%CI 23.4-30.1) testing. A negative hr-HPV-mRNA result at baseline was associated with HSIL-free survival (p < 0.001; hazard ratio (HR) 3.26, 95%CI 2.29-4.65; median follow-up time 43.0 months), regardless of cytology/histology results at baseline. Among participants with normal cytology, 93.3% of those with a negative hr-HPV-mRNA result were HSIL-free after 60 months, compared to 65.0% of those with a positive hr-HPV-mRNA result (p < 0.001). CONCLUSIONS: Hr-HPV-mRNA testing has increased specificity and similar sensitivity for the detection of HSIL+ in MSMLWH compared to hr-HPV-DNA-testing. Hr-HPV-mRNA testing has the potential to improve anal cancer screening effectiveness. Negative hr-HPV-mRNA results could allow for a safe extension of screening intervals.

doi.org/10.1016/j.ijmm.2026.151751Open accessPubMed 42925852Biomarkers