Abstract
Background: There is a growing interest in developing screening strategies for anal cancer to target high-risk populations. However, cytological and molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytology samples, the mRNA of three biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV) infection. The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade 2-3 (HSIL/AIN2-3) was also evaluated. Methods: Two-hundred and fifteen anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with a negative cytology and HPV test, 70 with cytology and biopsy showing low-grade SIL (LSIL/AIN1) and 75 with cytology and biopsy of HSIL/AIN2-3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed by reverse transcription qPCR. HPV detection was performed using the Xpert HPV Assay (Cepheid, Sunnyvale, CA). Adequate material for mRNA analysis was obtained from 199/215 (92.6%) samples. Results: mRNA expression for the three biomarkers was significantly higher in HSIL/AIN2-3 compared with LSIL/AIN1 or negative samples. The estimated specificity for the identification of HSIL/AIN2-3 for a sensitivity established at 70% was 44.7% (95% confidence interval [95%CI] 36.5-53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0-62.8%) for CDKN2A/p16. Conclusions: mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm the possible role of strategies based on mRNA detection in the secondary prevention of anal cancer. Funding Statement: This work was supported by the Instituto de Salud Carlos III (ICSIII)-Fondo de Investigacion Sanitaria and ERDF ‘One Way to Europe’ (grants PI15/00546 and PI17/00772). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the institutional ethical review board.
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