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Keywords = universal HPV typing assay

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15 pages, 1843 KB  
Article
Genotype-Specific HPV mRNA Triage Improves CIN2+ Detection Efficiency Compared to Cytology: A Population-Based Study of HPV DNA-Positive Women
by S. Sørbye, B. M. Falang, M. Antonsen and E. Mortensen
Pathogens 2025, 14(8), 749; https://doi.org/10.3390/pathogens14080749 - 30 Jul 2025
Cited by 1 | Viewed by 2029
Abstract
Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, [...] Read more.
Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. Full article
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18 pages, 2749 KB  
Article
Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022
by Raffaele Del Prete, Daniela Nesta, Francesco Triggiano, Mara Lorusso, Stefania Garzone, Lorenzo Vitulano, Sofia Denicolò, Francesca Indraccolo, Michele Mastria, Luigi Ronga, Francesco Inchingolo, Sergey K. Aityan, Kieu C. D. Nguyen, Toai Cong Tran, Ciro Gargiulo Isacco and Luigi Santacroce
Diagnostics 2024, 14(9), 968; https://doi.org/10.3390/diagnostics14090968 - 6 May 2024
Cited by 3 | Viewed by 2674
Abstract
Background: The current manuscript’s aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed [...] Read more.
Background: The current manuscript’s aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV’s molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41–50 and 51–60 years old, and finally, 44% of subjects were >60 years old. Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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18 pages, 2503 KB  
Article
Bacterial Outer Membrane Vesicles as a Platform for the Development of a Broadly Protective Human Papillomavirus Vaccine Based on the Minor Capsid Protein L2
by Silvia Tamburini, Yueru Zhang, Assunta Gagliardi, Gabriele Di Lascio, Elena Caproni, Mattia Benedet, Michele Tomasi, Riccardo Corbellari, Ilaria Zanella, Lorenzo Croia, Guido Grandi, Martin Müller and Alberto Grandi
Vaccines 2023, 11(10), 1582; https://doi.org/10.3390/vaccines11101582 - 11 Oct 2023
Cited by 9 | Viewed by 3017
Abstract
Human papillomaviruses (HPVs) are a large family of viruses with a capsid composed of the L1 and L2 proteins, which bind to receptors of the basal epithelial cells and promote virus entry. The majority of sexually active people become exposed to HPV and [...] Read more.
Human papillomaviruses (HPVs) are a large family of viruses with a capsid composed of the L1 and L2 proteins, which bind to receptors of the basal epithelial cells and promote virus entry. The majority of sexually active people become exposed to HPV and the virus is the most common cause of cervical cancer. Vaccines are available based on the L1 protein, which self-assembles and forms virus-like particles (VLPs) when expressed in yeast and insect cells. Although very effective, these vaccines are HPV type-restricted and their costs limit broad vaccination campaigns. Recently, vaccine candidates based on the conserved L2 epitope from serotypes 16, 18, 31, 33, 35, 6, 51, and 59 were shown to elicit broadly neutralizing anti-HPV antibodies. In this study, we tested whether E. coli outer membrane vesicles (OMVs) could be successfully decorated with L2 polytopes and whether the engineered OMVs could induce neutralizing antibodies. OMVs represent an attractive vaccine platform owing to their intrinsic adjuvanticity and their low production costs. We show that strings of L2 epitopes could be efficiently expressed on the surface of the OMVs and a polypeptide composed of the L2 epitopes from serotypes 18, 33, 35, and 59 provided a broad cross-protective activity against a large panel of HPV serotypes as determined using pseudovirus neutralization assay. Considering the simplicity of the OMV production process, our work provides a highly effective and inexpensive solution to produce universal anti-HPV vaccines. Full article
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10 pages, 2371 KB  
Article
Broad-Spectrum Detection of HPV in Male Genital Samples Using Target-Enriched Whole-Genome Sequencing
by Tengguo Li, Elizabeth R. Unger and Mangalathu S. Rajeevan
Viruses 2023, 15(9), 1967; https://doi.org/10.3390/v15091967 - 21 Sep 2023
Cited by 2 | Viewed by 2249
Abstract
Most human papillomavirus (HPV) surveillance studies target 30–50 of the more than 200 known types. We applied our recently described enriched whole-genome sequencing (eWGS) assay to demonstrate the impact of detecting all known and novel HPV types in male genital samples (n [...] Read more.
Most human papillomavirus (HPV) surveillance studies target 30–50 of the more than 200 known types. We applied our recently described enriched whole-genome sequencing (eWGS) assay to demonstrate the impact of detecting all known and novel HPV types in male genital samples (n = 50). HPV was detected in nearly all (82%) samples, (mean number of types/samples 13.6; range 1–85), and nearly all HPV-positive samples included types in multiple genera (88%). A total of 560 HPV detections (237 unique HPV types: 46 alpha, 55 beta, 135 gamma, and 1 mu types) were made. The most frequently detected HPV types were alpha (HPV90, 43, and 74), beta (HPV115, 195, and 120), and gamma (HPV134, mSD2, and HPV50). High-risk alpha types (HPV16, 18, 31, 39, 52, and 58) were not common. A novel gamma type was identified (now officially HPV229) along with 90 unclassified types. This pilot study demonstrates the utility of the eWGS assay for broad-spectrum type detection and suggests a significantly higher type diversity in males compared to females that warrants further study. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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