2022-RA-1502-ESGO Multiplexed biomarker detection using the QuantiGene assay in women living with HIV for cervical dysplasia detection. (20th October 2022)

• Record Type: Journal Article
• Authors: Skof, Anna Sophie; Mbuya, Wilbert; Mcharo, Ruby; Torres, Liset; France, John; Kroidl, Arne; Geldmacher, Christof; Kaufmann, Andreas M
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 2
• Page Start: A418
• Page End: A418
• Publication Date: 2022-10-20
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-ESGO.896
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Introduction/Background: Cervical cancer (CxCa) and its precursor lesions are caused by persistent infection with a high-risk(HR) Human Papillomavirus (HPV). Women living with HIV (WLWH) have a higher risk for cervical dysplasia and CxCa development. The high HPV prevalence in WLWH makes a HPV-PCR based screening non-efficient. Biomarker detection could be a possibility, to find woman at risk. We evaluated the biomarker-based QuantiGene-Molecular-Profiling-Histology assay (QG-MPH) in WLWH. Methodology: We analysed a representative subset of samples (n=301) from the prospective 2H-study including HIV+ and HIV- women. A cervical sample was collected using a cytobrush and fixed into ThinPrep/PreservCyt. The QG-MPH assay is based on the multiplexed Luminex bead-based technology platform (QuantiGene 2.0). It detects and quantifies the mRNA of 18 HR-HPV genotype-specific oncogenes, reference genes and cellular biomarkers including proliferation, tumour stem cell and tumour markers to predict the dysplasia stage, simultaneously. Results: HIV coinfection was significantly associated with increased mRNA expression of the following biomarkers in HR-HPV+ women without cervical lesions: leading HPV-E7 (p=0.0019), p16 (p=0.022), STMN1 (p=0.0039), MCM2 (p=0.015), KRT7 (p=0.0035) and KRT17 (p=0.014). In cervical cancer cases (HIV+=19, HIV-=18) only the expression of Nanog mRNA was different (p=0.022). Using the risk score developed on a HIV- cohort led to false positive detection (CIN3+) of 68.8% (n=22) in WLWH without lesions. Logistic regression analyses showed best markers for CxCa detection in HIV+ patients in our cohort were BIRC5, KRT17, MMP7 and p53 with a combined AUC of 0.93 (sensitivity=95%, specificity=82.0%). Conclusion: Viral oncogene expression is increased in HR-HPV+ WLWH without cervical lesions. Biomarker evaluation has the potential to overcome problems of HPV PCR-based screening in WLWH. However, risk score adaptation is needed as biomarker expression varies between HIV+ and HIV- patients. Further studies with higher sample number are warranted to confirm the best markers and risk scores by QG-MPH analysis.