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Cervical Cancer Screening: Current Practices and Future Perspectives

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 1 October 2026 | Viewed by 4025

Special Issue Editor


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Guest Editor
1st Department of Obstetrics & Gynecology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece
Interests: gynecologic oncology; cervical cancer screening; HPV-related diseases

Special Issue Information

Dear Colleagues,

Cervical carcinoma is caused by a persistent high-risk human papillomavirus (HPV) infection. This scientifically proven statement has led, in recent decades, to the development of two very important innovations, i.e., the HPV vaccine and the HPV-based cervical cancer screening. The latter refers to the implementation of various screening tests, developed and validated in large-scale trials, based on the detection of HPV nucleic acids, into organized cervical cancer screening. 

In 2018, the WHO launched a strategy for the elimination of cervical cancer utilizing the abovementioned tools and novel advancements regarding the treatment of invasive cervical cancer. This strategy is based on three goals, namely, the achievement of a 90% coverage of girls up to the age of 15 with the vaccine against HPV, the coverage of 70% of women with a high-performance HPV-based screening test twice in their lifetime, and the proper treatment of at least 90% of women diagnosed with cervical (pre)cancer.

 This Special Issue will be dedicated to the second pillar of the WHO goals for cervical cancer elimination, i.e., to cervical cancer secondary prevention or cervical cancer screening, and will accept manuscripts investigating, but not being limited to, the following:

  • The performance of screening algorithms;
  • Novel screening modalities (for primary screening or triage);
  • Self-sampling;
  • Modelling on the projection of screening in the context of HPV vaccination;  
  • Screening for underserved populations;
  • Screening for immunocompromised populations;
  • Screening for populations vaccinated against HPV;   
  • Performance of AI-assisted colposcopy;    
  • Cervical precancer treatment and follow-up. 

I strongly encourage researchers in basic science, public health, or clinical science involved with HPV, cervical disease, and screening to submit their work to be included in this Special Issue; I hope that in this way we will be able to produce a collection of scientific publications presenting up-to-date and innovative research, which would reflect the present and future landscape of cervical cancer screening, from a multi-disciplinary perspective.

Dr. Kimon Chatzistamatiou
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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

  • cervical cancer screening
  • cervical carcinogenesis
  • human papillomavirus
  • HPV primary screening
  • self-sampling
  • triage of HPV-positive
  • post-conization follow-up
  • screening for immunocompromised women
  • screening for vac-cinated women

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Published Papers (4 papers)

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Research

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18 pages, 2106 KB  
Article
MicroRNA-Based Triage of HPV-Positive Women Using Liquid-Based Cytology: Diagnostic Performance and Network-Level Insights
by Justyna Pisarska, Aleksandra Kożańska, Rafał Rzepka and Katarzyna Baldy-Chudzik
Cancers 2026, 18(4), 559; https://doi.org/10.3390/cancers18040559 - 9 Feb 2026
Viewed by 575
Abstract
Background: Human papillomavirus (HPV)-based screening has substantially improved sensitivity for cervical cancer detection but remains limited by low specificity, leading to unnecessary colposcopy referrals. MicroRNAs (miRNAs) represent promising biomarkers for improving triage of HPV-positive women. This study evaluated the diagnostic and regulatory roles [...] Read more.
Background: Human papillomavirus (HPV)-based screening has substantially improved sensitivity for cervical cancer detection but remains limited by low specificity, leading to unnecessary colposcopy referrals. MicroRNAs (miRNAs) represent promising biomarkers for improving triage of HPV-positive women. This study evaluated the diagnostic and regulatory roles of selected miRNAs in cervical lesion progression using liquid-based cytology (LBC) specimens. Methods: Expression of six biologically relevant miRNAs (miR-15a-5p, miR-16-5p, miR-20b-5p, miR-155-5p, miR-34a-5p, and miR-140-3p) was analyzed across NILM, CIN II, CIN III, and cervical cancer (CC) samples. All miRNA analyses were performed using residual cellular material derived from the same liquid-based cytology (LBC) specimens collected during the HPV screening visit, without requiring any additional sampling prior to colposcopy. Diagnostic performance was assessed using ROC analysis. To capture regulatory dynamics beyond expression magnitude, correlation, and differential correlation (Δρ), network analyses were applied. Results: Stage-dependent changes in miRNA expression were observed across disease categories; however, expression magnitude alone did not fully explain diagnostic performance. Upregulated miRNAs, particularly miR-16-5p, miR-20b-5p, and miR-155-5p, demonstrated high diagnostic accuracy for distinguishing NILM from high-grade lesions and invasive cancer. In contrast, downregulated miRNAs showed limited diagnostic utility. Correlation analyses revealed progressive remodeling of miRNA co-expression networks, with the most pronounced changes occurring during the CIN II–to–CIN III transition. Notably, miRNAs with strong diagnostic performance did not uniformly function as network hubs, indicating distinct roles as biomarkers versus regulators of network dynamics. Conclusions: Cervical lesion progression is characterized not only by changes in miRNA expression levels but also by stage-specific reorganization of miRNA regulatory networks. Integrating diagnostic performance with network-level analysis enables improved identification of clinically robust triage markers and provides additional insight into regulatory instability associated with progression. Full article
(This article belongs to the Special Issue Cervical Cancer Screening: Current Practices and Future Perspectives)
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16 pages, 855 KB  
Article
Human Papillomavirus Self-Sampling Attitudes Amongst Women Living with HIV Prior to a Self-Sampling Intervention
by Sofia Nicolls, Emma Karlsen, Isabelle Boucoiran, Shariq Haider, Valérie Martel-Laferrière, Vanessa Poliquin, Marie-Louise Vachon, Sharon Walmsley, Alexander Wong, Sean Yaphe, Mark H. Yudin, Gina Ogilvie, Deborah Money and Elisabeth McClymont
Cancers 2026, 18(1), 14; https://doi.org/10.3390/cancers18010014 - 19 Dec 2025
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Abstract
Background/Objectives: Our objective was to determine the acceptability of and attitudes towards HPV self-sampling among women with HIV and investigate any associations between self-sampling attitudes and participant demographic and clinical characteristics. Methods: Women with HIV aged 18–45 were given a description of [...] Read more.
Background/Objectives: Our objective was to determine the acceptability of and attitudes towards HPV self-sampling among women with HIV and investigate any associations between self-sampling attitudes and participant demographic and clinical characteristics. Methods: Women with HIV aged 18–45 were given a description of HPV self-sampling and instructions on how to self-collect the sample. Participants completed a questionnaire assessing their perceptions of the acceptability and comfort of HPV self-sampling before using the self-sampling methodology. Responses were based on a 5-point Likert scale (strongly agree to strongly disagree) for each statement. Participants’ characteristics were included in bivariate analysis. Chi-square and Fisher’s exact tests were used to assess associations between questionnaire results and participant characteristics. Results: Of the 117 completed questionnaires, 79.6% of participants had a CD4+ T cell count ≥ 500 cells/mm3. Participants’ median age was 39 (IQR 34–43). One hundred participants (85.5%) felt confident they could collect their samples correctly, and 77.8% did not think they would experience difficulties with self-collection. Most participants (68.4%) preferred to self-collect their sample instead of provider-collected sampling. Ninety-six participants (82.1%) agreed they would likely use self-collection methods for future cervical screening. Many participants were concerned about receiving a positive HPV result (68.4%), passing HPV on to their partner(s) (75.7%), and disclosing their HPV status to friends/family (49.6%). Conclusions: Women with HIV seem to be accepting of HPV self-sampling as a cervical cancer screening methodology; however, many participants were concerned about the implications associated with a positive HPV test result. Full article
(This article belongs to the Special Issue Cervical Cancer Screening: Current Practices and Future Perspectives)
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20 pages, 3357 KB  
Article
Noninvasive Cell Population Profiling of Normal and Dysplastic Cervical Biofluids by Multicolor Flow Cytometry as a Promising Tool for Companion Diagnostics
by Christoph Berger, Wolf Dietrich, Manuela Richter, Florian Kellner, Christian Kühne and Katharina Strasser
Cancers 2025, 17(20), 3328; https://doi.org/10.3390/cancers17203328 - 15 Oct 2025
Viewed by 1140
Abstract
Background/Objectives: Cervical Pap smears are routinely used to detect cellular abnormalities as a cervical cancer screening tool and to assess the presence of HPV for risk stratification of the disease. Here, we aimed to extend the applications of this sampling procedure by [...] Read more.
Background/Objectives: Cervical Pap smears are routinely used to detect cellular abnormalities as a cervical cancer screening tool and to assess the presence of HPV for risk stratification of the disease. Here, we aimed to extend the applications of this sampling procedure by combining it with multicolor flow cytometry to characterize cell populations across cervical cancer disease stages. Methods: Cervical Pap smears from 30 patients with various disease stages ranging from normal to intraepithelial neoplasia up to treated cancers were analyzed as biofluids using multicolor flow cytometry. Individual samples were evaluated, and statistical analyses were performed over all sample stages. Cancer cell lines (CaSki, SiHa, HeLa, A549, U2OS) were examined as tumor cell controls. Results: Cervical biofluids were subdivided into cell populations according to their scattering properties and the expression of specific biomarkers: EpCAM and cytokeratin 8 for epithelial cells from tumors as well as healthy ectocervical and endocervical regions, and CD45 for immune cells. Discrimination of tumor cells was facilitated with cancer cell lines. Statistical analysis revealed that the composition of cell populations differs among disease stages, whereas treated cancer samples were consistently associated with a reduction in squamous epithelial cells and an increase in immune cells compared to normal samples. Conclusions: Herein, we identified the major cell populations in cervical biofluid samples and demonstrated that this method can detect changes in the cellular composition across different disease stages. This approach could be further exploited in cancer research and potentially serve as a companion diagnostic tool in tumor development, progression and during treatment. Full article
(This article belongs to the Special Issue Cervical Cancer Screening: Current Practices and Future Perspectives)
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Review

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20 pages, 1043 KB  
Review
Analysis of Molecular Markers of HPV Infection Persistence: A Narrative Review
by Dominik Pruski, Sonja Millert-Kalińska, Katarzyna Wszołek, Victoria Musiałowicz, Jacek P. Grabowski, Robert Jach, Mustafa Zelal Muallem, Jalid Sehouli and Marcin Przybylski
Cancers 2026, 18(6), 981; https://doi.org/10.3390/cancers18060981 - 18 Mar 2026
Viewed by 910
Abstract
Background: Persistent infection with high-risk human papillomavirus (hr-HPV) is the necessary agent of cervical cancer, yet its molecular definition remains heterogeneous. Multiple molecular approaches have been developed to characterize HPV persistence, including repeated detection of viral DNA, assessment of viral oncogene expression, and [...] Read more.
Background: Persistent infection with high-risk human papillomavirus (hr-HPV) is the necessary agent of cervical cancer, yet its molecular definition remains heterogeneous. Multiple molecular approaches have been developed to characterize HPV persistence, including repeated detection of viral DNA, assessment of viral oncogene expression, and analysis of HPV-related DNA methylation. These approaches originate from different scientific traditions and reflect distinct conceptualizations of persistence. Objective: To synthesize and compare molecular methods used to detect persistent HPV infection through a narrative review and to clarify how different biomarkers conceptualize HPV persistence and disease progression. Methods: We conducted a narrative review in accordance with the RAMESES guidelines. Medline, Scopus, and the Cochrane Library were searched for original studies published between 2016 and 2025 investigating molecular markers of HPV persistence. An interpretive synthesis was performed to identify research traditions, underlying assumptions, and clinical implications. Results: Three major molecular narratives were identified. Persistent DNA positivity defines persistence as repeated detection of the same HR-HPV genotype over time and reflects an epidemiological–virological perspective with high sensitivity but limited specificity. Persistent oncogene expression, assessed by E6/E7 mRNA detection, conceptualizes persistence as active viral oncogenic activity and shows improved specificity for clinically relevant lesions. Persistent epigenetic imprint, measured by DNA methylation of viral and host genes, captures cumulative biological effects of long-term infection and is strongly associated with high-grade lesions and cervical cancer. These narratives represent complementary stages along a continuum of molecular persistence. Conclusions: Molecular markers of HPV persistence reflect the evolving understanding of cervical carcinogenesis, progressing from repeated viral DNA detection to oncogenic activity and stable epigenetic alterations. These complementary biomarkers represent different biological stages of persistent infection and may improve risk stratification in HPV-based screening and triage strategies. Full article
(This article belongs to the Special Issue Cervical Cancer Screening: Current Practices and Future Perspectives)
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