Vassiliki C. Pitiriga

Evaluation of the PreTect HPV-Proofer E6/E7 mRNA Assay for the Detection of Precancerous Cervical Lesions in the Greek Female Population

Cervical cancer remains a significant public health concern, ranking as the 10th most common cancer among women in Greece. Current screening programs primarily rely on cytology and HPV DNA testing; however, their positive predictive value (PPV) for detecting high-grade cervical intraepithelial neoplasia (CIN2+) remains limited. This study aimed to compare the clinical performance of the HPV mRNA test with that of the HPV DNA test, focusing on their PPV for detecting CIN1+ lesions in a cohort of Greek women. A total of 114 women undergoing routine cervical cancer screening were tested using an HPV DNA assay (detecting 41 HPV types), Pap smear, and were referred for colposcopy and biopsy when indicated. Among them, 29 women aged 18 to 65 years (mean age: 35.1 ± 10.8 years) who tested positive for one or more of the five high-risk HPV types (16, 18, 31, 33, 45) were further assessed using the PreTect HPV-Proofer® mRNA assay. Of these 29 women, 11 (37.9%) had negative biopsy findings, 16 (55.2%) were diagnosed with CIN1, and 2 (6.9%) with CIN2, corresponding to a positive predictive value (PPV) of 55.2% for CIN1 and 6.9% for CIN2 with the HPV DNA test. Among the 17 women who tested positive for HPV mRNA, 13 were diagnosed with CIN1 and 2 with CIN2. Among the 12 women who tested negative for HPV mRNA, 3 had CIN1 and 9 had negative biopsy results. Based on these findings, the PPV of the HPV mRNA test for CIN1 was 76.5%, the negative predictive value (NPV) was 75.0%, and the clinical sensitivity for CIN1 was 81.3%. For CIN2, the PPV was 11.8%, while the clinical sensitivity and NPV were 100%. These findings highlight the potential of HPV mRNA testing to improve specificity in cervical cancer screening by more accurately identifying clinically significant lesions and reducing unnecessary colposcopies.

Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review

The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.