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.
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