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Pathogens
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Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections
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Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections

A Special Issue of Pathogens (ISSN 2076-0817) belonging to the section "Viral Pathogens".

Deadline for manuscript submissions: 10 March 2027 | Viewed by 4678

Editors

Dr. Zhengchun Lu

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA
Interests: human papilloma virus; early cancer detection; clinical diagnosis; molecular microbiology; molecular pathology
Prof. Dr. Guang Fan

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA
Interests: hematopathology; leukemia and lymphoma; clinical microbiology; laboratory management

Special Issue Information

Dear Colleagues,

High-risk human papillomaviruses (hrHPVs) are responsible for nearly all cervical cancers and contribute substantially to a wide spectrum of anogenital and other HPV-associated cancers worldwide. While cervical cancer remains the most recognized outcome, hrHPV also causes significant disease across multiple anatomic sites, underscoring the need for integrated research spanning epidemiology, diagnostics, prevention, and treatment. In alignment with global public health goals—including the World Health Organization (WHO) initiative to eliminate cervical cancer as a public health problem—this Special Issue aims to highlight advances that deepen our understanding of HPV pathogenesis, improve screening and triage strategies, and support equitable implementation of diagnostic and clinical approaches in diverse populations and healthcare settings. We welcome original research, reviews, and translational studies that explore novel testing technologies, biomarkers, vaccines, and therapeutic interventions, with the overarching goal of reducing the global burden of HPV-associated disease.

Dr. Zhengchun Lu
Prof. Dr. Guang Fan
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • high-risk HPV
  • HPV-associated diseases
  • screening and diagnostics
  • HPV epidemiology
  • therapeutic and preventive strategies

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Published Papers (5 papers)

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Research

13 pages, 891 KB  
Article
Multiple High-Risk HPV Infections and Opportunistic HPV Prevalence Among Women Aged 18–25 Years with NILM, ASC-US, or LSIL Cytology: A 2024 Cross-Sectional Study
by Erik Kudela, Tomas Rokos, Erik Kozubik, Terezia Pribulova, Filip Piovar and Kamil Biringer
Pathogens 2026, 15(9), 949; https://doi.org/10.3390/pathogens15090949 - 7 Sep 2026
Viewed by 184
Abstract
Multiple high-risk human papillomavirus (hrHPV) infections in young women are poorly characterized across age and cytology, particularly with partial genotyping. We assessed multiple hrHPV infections among HPV-positive women aged 18–25 years with NILM, ASC-US, or LSIL; the secondary objective was hrHPV positivity among [...] Read more.
Multiple high-risk human papillomavirus (hrHPV) infections in young women are poorly characterized across age and cytology, particularly with partial genotyping. We assessed multiple hrHPV infections among HPV-positive women aged 18–25 years with NILM, ASC-US, or LSIL; the secondary objective was hrHPV positivity among electively tested women with NILM. This retrospective cross-sectional study analyzed 2024 laboratory data from northern Slovakia. Of 7613 unique women, 7574 met cytological eligibility criteria; 804 underwent cobas 4800 testing, and 295 were hrHPV-positive. Multiple infection, defined as concurrent detection of at least two reportable categories (HPV16, HPV18, or other hrHPV), occurred in 69/295 women (23.4%; 95% CI, 18.9–28.5%). No statistically detectable variation was observed by cytology after age adjustment (p = 0.471) or by age after cytology adjustment (p = 0.891). Among women with multiple infections, HPV16 combined with other hrHPV was the most frequent pattern (30/69; 43.5%). Among 396 electively tested women with NILM, 75 were hrHPV-positive (18.9%; 95% CI, 15.4–23.1%); positivity was lower at ages 23–25 than 18–22 (10.6% vs. 26.6%; OR, 0.33; 95% CI, 0.19–0.57; p < 0.001). The NILM estimate describes a self-selected preventive cohort and is not population-representative. Full article
(This article belongs to the Special Issue Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections)
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12 pages, 231 KB  
Article
Repeated Detection of Vaccine-Preventable Anal HPV Genotypes in a Screened Cohort: A Retrospective Observational Study
by Alberto Rizzo, Davide Moschese, Federica Salari, Luca Carsana, Samuel Lazzarin, Andrea Cavallo, Chiara Fusetti, Loriana Morelli, Francesco Caruso, Alessandra Lombardi, Andrea Giacomelli, Manuela Nebuloni, Alberto Dolci and Andrea Gori
Pathogens 2026, 15(7), 730; https://doi.org/10.3390/pathogens15070730 - 10 Jul 2026
Viewed by 439
Abstract
The clinical relevance of concurrent vaccine-preventable anal HPV genotype infections, particularly for short-term repeated detection and cytologic outcomes in screened high-risk populations, remains uncertain. We performed a single-centre retrospective study of 145 adults with at least one 9-valent vaccine-preventable anal HPV genotype at [...] Read more.
The clinical relevance of concurrent vaccine-preventable anal HPV genotype infections, particularly for short-term repeated detection and cytologic outcomes in screened high-risk populations, remains uncertain. We performed a single-centre retrospective study of 145 adults with at least one 9-valent vaccine-preventable anal HPV genotype at baseline and repeat HPV DNA testing and cytology approximately 12 months later. Baseline infections were classified as single- or multiple-genotype infections. Outcomes included clearance of all baseline vaccine-preventable genotypes, genotype-specific repeated detection, detection of new vaccine-preventable genotypes, complete HPV negativity, and cytologic regression or progression. At baseline, 70 participants (48.3%) had single and 75 (51.7%) had multiple genotype infections; most were male (95.2%) and people living with HIV (88.3%), reflecting a highly selected anal HPV-screened cohort. Multiple infections were associated with more frequent abnormal baseline cytology (69.3% vs. 45.7%). At follow-up, clearance of all baseline vaccine-preventable genotypes was more common after single than multiple infections (34.3% vs. 12.0%). Complete HPV negativity was also more frequent after single infection (24.3% vs. 4.0%), although this stringent endpoint is intrinsically more difficult to achieve in individuals with multiple baseline infections. New vaccine-preventable genotype detection did not differ significantly between groups. Genotype-specific repeated detection was generally similar between groups, except for HPV58, a finding based on small subgroup numbers. Cytologic regression was more frequent after single infection, but not statistically significant. Multiple vaccine-preventable anal HPV genotype infections were associated with greater baseline cytologic abnormality and lower clearance of baseline vaccine-preventable genotypes at 12 months. Given the retrospective design, selected population, limited event counts, and residual confounding, these findings should be interpreted as hypothesis-generating and do not prove impaired biological clearance. Full article
(This article belongs to the Special Issue Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections)
18 pages, 447 KB  
Article
Five-Year Risk of CIN3+ After CIN1 Biopsy in a Norwegian Screening Setting: Comparison of CIN1 Diagnosed in a Single Calendar Year and in Two Consecutive Calendar Years
by Sveinung Wergeland Sørbye, Mona Antonsen and Elin Richardsen
Pathogens 2026, 15(6), 657; https://doi.org/10.3390/pathogens15060657 - 22 Jun 2026
Viewed by 727
Abstract
Cervical intraepithelial neoplasia grade 1 (CIN1) is usually managed conservatively, but uncertainty remains about the subsequent risk of clinically significant high-grade disease, particularly after repeated CIN1. We conducted a retrospective population-based cohort study using anonymized cervical cytology, HPV, and histopathology records from Northern [...] Read more.
Cervical intraepithelial neoplasia grade 1 (CIN1) is usually managed conservatively, but uncertainty remains about the subsequent risk of clinically significant high-grade disease, particularly after repeated CIN1. We conducted a retrospective population-based cohort study using anonymized cervical cytology, HPV, and histopathology records from Northern Norway from 2011 to 2025. We described temporal trends in screening-related outcomes and estimated the 5-year risk of CIN3+ after histologically confirmed CIN1 diagnosed in a single calendar year or in two consecutive calendar years. Across 2011–2025, the annual datasets comprised 334,471 screening records; 35,796 had ASC-US+ cytology (10.7%), 29,723 had a positive HPV test (8.9%), 35,416 underwent biopsy (10.6%), and 7870 were diagnosed with CIN2+ (2.4%). HPV positivity increased from 0.9% in 2011 to 15.7% in 2025, whereas CIN2+ detection peaked at 3.1% in 2018 and declined to 1.8% in 2025. In person-based analyses, the 5-year risks after CIN1 diagnosed in a single calendar year versus two consecutive calendar years were 4.3% versus 3.4% for CIN3+, 0.2% versus 0.1% for cervical cancer, and 15.4% versus 14.3% for CIN2+. Repeated CIN1 was not associated with higher subsequent CIN3+ risk, supporting conservative, risk-based follow-up after CIN1 biopsy. Full article
(This article belongs to the Special Issue Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections)
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19 pages, 1487 KB  
Article
Genotype-Specific HPV mRNA Triage Improves Colposcopy Efficiency Compared with Cytology and ATHENA-Derived Triage: A Population-Based Study of HPV DNA-Positive Women
by Sveinung Wergeland Sørbye, Bente Marie Falang, Mona Antonsen and Elin Richardsen
Pathogens 2026, 15(6), 584; https://doi.org/10.3390/pathogens15060584 - 28 May 2026
Cited by 1 | Viewed by 658
Abstract
Background: Effective triage of HPV DNA-positive women is needed to reduce unnecessary colposcopies while maintaining cervical cancer prevention. We evaluated genotype-specific 7-type HPV E6/E7 mRNA triage in a real-world screening cohort. Methods: In this population-based single-centre study at the University Hospital of North [...] Read more.
Background: Effective triage of HPV DNA-positive women is needed to reduce unnecessary colposcopies while maintaining cervical cancer prevention. We evaluated genotype-specific 7-type HPV E6/E7 mRNA triage in a real-world screening cohort. Methods: In this population-based single-centre study at the University Hospital of North Norway, 42,791 women underwent primary screening with the cobas HPV DNA assay during the period 2019–2024. Among 2370 HPV DNA-positive women, reflex cytology, 7-type HPV mRNA testing, and an ATHENA-derived triage strategy were compared using histologically confirmed CIN3+ through 31 December 2025 as the endpoint. Results: CIN3+ was detected in 60/2370 women (2.5%). Test positivity was 47.0% for cytology, 54.7% for ATHENA-derived triage, and 33.4% for HPV mRNA. Sensitivity was 78.3%, 86.7%, and 73.3%; specificity was 53.8%, 46.1%, and 67.7%; and PPV was 4.2%, 4.0%, and 5.6%, respectively. Colposcopies per CIN3+ detected were 23.7, 24.9, and 18.0. Conclusions: HPV mRNA triage improved referral precision and colposcopy efficiency, but with lower sensitivity than ATHENA-derived triage. These findings support 7-type HPV mRNA testing as a potentially useful molecular triage option where structured follow-up is feasible. Full article
(This article belongs to the Special Issue Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections)
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21 pages, 3192 KB  
Article
The Exploration of Therapeutic Antivirals for Human Papillomavirus in the Last 40 Years: Bibliometric Research
by Zixiao Jiang, Liangrui Jin, Chengjun Wu, Zhenqing Li, Zhangrong Lou and Peng Qu
Pathogens 2026, 15(3), 265; https://doi.org/10.3390/pathogens15030265 - 2 Mar 2026
Viewed by 1970
Abstract
Human papillomavirus (HPV) is a well-known carcinogenic DNA virus, responsible for about 4% of all cancer cases globally. Effective antiviral treatments for those who are already infected with HPV are still in their early stages, despite the fact that prophylactic vaccinations have shown [...] Read more.
Human papillomavirus (HPV) is a well-known carcinogenic DNA virus, responsible for about 4% of all cancer cases globally. Effective antiviral treatments for those who are already infected with HPV are still in their early stages, despite the fact that prophylactic vaccinations have shown impressive success in preventing new infections. Effective treatments for HPV-related malignancies are also hampered by the fact that current articles address a wide spectrum of pathways but lack thorough systematic studies. In this work, we use bibliometric techniques to examine research trends and innovative approaches in the development of HPV antivirals over the last 40 years. Our results are intended to offer insightful information and direct future research into effective antiviral treatments for HPV-induced cancers. Full article
(This article belongs to the Special Issue Epidemiology, Diagnostics, and Therapeutics of High-Risk Human Papillomavirus (HPV) Infections)
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