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New Strategies to Improve the Detection of Human Papillomavirus (HPV) Persisting Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 3530

Special Issue Editor

Dr. Marianna Martinelli

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Milano-Bicocca, Cadore 48 Street, 20900 Monza, Italy
Interests: human papillomavirus; cervical cancer; HPV-related cancers; sexually transmitted infections; viral diseases

Special Issue Information

Dear Colleagues,

The introduction of human papillomavirus (HPV) primary testing in cervical cancer screening programs has certainly improved clinical sensitivity as compared to cytology (Pap test) but does not allow for discriminating between women with transient infections and those truly at risk of developing cancer. For this reason, HPV-positive women are presently triaged by performing a Pap test from the same starting cervical sample, and only those with confirmed abnormal cervical cytology undergo colposcopy. HPV infections are particularly common in young sexually active women, so it is very important to avoid the unnecessary overtreatment of clinically irrelevant infections. The introduction of more standardized and reproducible molecular biomarkers, such as full-genotyping, genotype-specific HR-HPV viral loads, oncogenic transcript (E6/E7 mRNA) quantification, the definition of viral or human methylation status, and research on specific viral mutation and viral variants, could improve the risk stratification in cervical cancer screening programs helping to discriminate between transient and persisting infections.

This Special Issue aims to collect research contributions or review articles that involve the description of, development of, or new molecular potential biomarkers in this field.

Dr. Marianna Martinelli
Guest Editor

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Keywords

  • human papillomavirus
  • HPV
  • viral load
  • genotyping
  • oncogenic transcripts
  • biomarkers

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Published Papers (3 papers)

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Research

15 pages, 2772 KiB  
Article
Molecular Detection of Human Papillomavirus (HPV) and Other Sexually Transmitted Pathogens in Cervical and Self-Collected Specimens
by Chiara Giubbi, Marianna Martinelli, Michelle Rizza, Maria Letizia Di Meo, Ruth Chinyere Njoku, Federica Perdoni, Giulio Mannarà, Rosario Musumeci, Robert Fruscio, Fabio Landoni and Clementina Elvezia Cocuzza
Int. J. Mol. Sci. 2025, 26(3), 1296; https://doi.org/10.3390/ijms26031296 - 3 Feb 2025
Viewed by 930
Abstract
This study investigated the detection of high-risk Human Papillomavirus (hrHPV) and seven other pathogens associated with sexually transmitted infections (STIs) in matched clinician-collected cervical samples and self-taken vaginal and urine specimens collected from 342 asymptomatic women referred to colposcopy to evaluate (i) the [...] Read more.
This study investigated the detection of high-risk Human Papillomavirus (hrHPV) and seven other pathogens associated with sexually transmitted infections (STIs) in matched clinician-collected cervical samples and self-taken vaginal and urine specimens collected from 342 asymptomatic women referred to colposcopy to evaluate (i) the concordance in the molecular detection of investigated pathogen in three different sample types; (ii) the analytical sensitivity and specificity of STIs detection on self-samples; and (iii) the distribution of STIs in hrHPV-positive and hrHPV-negative women. Pathogens detection was performed using Anyplex™II HR and Anyplex™II STI-7e, respectively. Good/substantial agreement was observed between cervical and self-taken samples in detecting hrHPV (κ = 0.870 and κ = 0.773 for vaginal and urine). The agreement between cervical and self-taken samples for detecting STIs was found to be significant (κ = 0.779 and κ = 0.738 for vaginal and urine), with almost perfect agreement between urine and vaginal specimens (κ = 0.899). The positivity rate for all investigated STIs was found to be higher in hrHPV-positive compared to hrHPV-negative women. In conclusion, self-sampling proved to be a valid alternative to cervical samples to detect hrHPV and STIs, but further studies are required to evaluate the role of STI coinfections in cervical lesions development and progression. Full article
(This article belongs to the Special Issue New Strategies to Improve the Detection of Human Papillomavirus (HPV) Persisting Infections)
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12 pages, 906 KiB  
Article
Transcriptomic Analysis of HPV-Positive Oesophageal Tissue Reveals Upregulation of Genes Linked to Cell Cycle and DNA Replication
by Muhammad Osama Shafiq, Muharrem Okan Cakir, Ugur Bilge, Yasmin Pasha and G. Hossein Ashrafi
Int. J. Mol. Sci. 2025, 26(1), 56; https://doi.org/10.3390/ijms26010056 - 24 Dec 2024
Viewed by 897
Abstract
Human papillomavirus (HPV) is a prevalent sexually transmitted infection, implicated in various cancers, yet its influence in non-cancerous oesophageal tissue remains unclear. This study aims to investigate the gene expression changes associated with high-risk HPV (HR-HPV) in non-cancerous oesophageal tissue to elucidate potential [...] Read more.
Human papillomavirus (HPV) is a prevalent sexually transmitted infection, implicated in various cancers, yet its influence in non-cancerous oesophageal tissue remains unclear. This study aims to investigate the gene expression changes associated with high-risk HPV (HR-HPV) in non-cancerous oesophageal tissue to elucidate potential early oncogenic mechanisms. Using RNA sequencing, we compared transcriptomic profiles of HPV-positive and HPV-negative non-cancerous oesophageal tissues. Differential gene expression analysis revealed significant upregulation of cell cycle and DNA replication pathways in HPV-positive samples, specifically involving key genes such as CCNA2, DSN1, and MCM10, which are known to regulate cellular proliferation and genomic stability. Additionally, kinase and transcription factor enrichment analyses highlighted HR-HPV-associated regulatory molecules, including E2F4 and CSNK2A1, suggesting HPV’s role in modulating host cell cycle control. These findings support the hypothesis that HPV infection may initiate cellular alterations in oesophageal tissue, potentially predisposing it to malignancy. This study contributes to understanding HPV’s impact in non-cancerous tissues and identifies possible biomarkers for early HPV-related cellular changes, offering insights into HPV-driven cancer development beyond traditionally associated sites. Full article
(This article belongs to the Special Issue New Strategies to Improve the Detection of Human Papillomavirus (HPV) Persisting Infections)
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14 pages, 948 KiB  
Article
Could APTIMA mRNA Assay Contribute to Predicting Cervical Bacterial Sexually Transmitted Co-Infections? A Colposcopy Population Study
by George Valasoulis, Abraham Pouliakis, Ioulia Magaliou, Dimitrios Papoutsis, Nikoletta Daponte, Chrysoula Margioula-Siarkou, Georgios Androutsopoulos, Alexandros Daponte and Georgios Michail
Int. J. Mol. Sci. 2024, 25(23), 13146; https://doi.org/10.3390/ijms252313146 - 6 Dec 2024
Cited by 1 | Viewed by 1081
Abstract
In addition to chronic hrHPV anogenital infection, continuing inflammatory cervical changes are intrinsic in the development of precancerous lesions. In younger women, much of this inflammatory background parallels the progressive maturation of squamous metaplasia, often rendering treatment interventions redundant; however, patients with persistent [...] Read more.
In addition to chronic hrHPV anogenital infection, continuing inflammatory cervical changes are intrinsic in the development of precancerous lesions. In younger women, much of this inflammatory background parallels the progressive maturation of squamous metaplasia, often rendering treatment interventions redundant; however, patients with persistent cervical precancer, as well as those harboring invasive bacterial pathogens, might benefit from controlling the active inflammatory process by shortening the HPV natural cycle and avoiding subsequent cervical surgery. In a colposcopy population of 336 predominantly young asymptomatic individuals, we explored the impact of molecularly detected bacterial STIs on HPV DNA and APTIMA positivity rates using validated assays. In the multivariable analysis, several largely anticipated epidemiological factors were related to STI positivity. In this cohort, the HPV DNA test illustrated better performance for the prediction of STI positivity than the corresponding APTIMA test (sensitivity 52.94% vs. 33.82%), while inversely, the APTIMA test was more indicative of bacterial STI negativity than the HPV DNA test (specificity 77% vs. 60%). In addition, no significant differences between these two molecular assays were documented in terms of PPV, NPV, and overall accuracy. Despite the high Ureaplasma urealyticum and low Chlamydia trachomatis prevalence recorded in this study’s population, which is among the first assessing the co-variation of bacterial STI expression with established HPV biomarkers, the APTIMA assay did not predict concurrent bacterial STIs superiorly compared with an established HPV DNA assay. Full article
(This article belongs to the Special Issue New Strategies to Improve the Detection of Human Papillomavirus (HPV) Persisting Infections)
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