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Diagnostics
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Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers
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Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 3703

Special Issue Editors

Dr. Anna Daniela Iacobone

E-Mail Website
Guest Editor
Preventive Gynecology Unit, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
Interests: gynecologic oncology; lower genital tract disease; HPV; colposcopy; ultrasound
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Tagliabue

E-Mail Website
Guest Editor
Department of Otorhinolaryngology and Head and Neck Surgery, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy
Interests: HPV-related oropharyngeal cancers; head and neck pathology

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue entitled “Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers”. Human papillomavirus (HPV) infection is a well-established cause of several malignancies, including cervical, vaginal, vulvar, anal, penile, and oropharyngeal cancers. Despite major advances in prevention, many questions remain regarding the biological mechanisms underlying the progression from infection to cancer, the identification of individuals at highest risk, and the development of tools to improve early detection.

This Special Issue aims to explore the most recent advances in understanding the pathogenesis of HPV-related cancers and pre-cancers, with a particular focus on early diagnosis. We welcome original research articles and reviews addressing molecular mechanisms, host–virus interactions, and the role of the microbiome, as well as the development and validation of novel molecular assays, biomarkers of persistence or progression, and prognostic indicators of treatment outcomes and recurrence risk.

In this Special Issue, we particularly encourage contributions on translational approaches that may guide clinical practice and improve patient management.

We look forward to hearing from you.

Dr. Anna Daniela Iacobone
Dr. Marta Tagliabue
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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. Diagnostics 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 2600 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

  • HPV-related cancer
  • molecular diagnostics
  • precancerous lesions
  • biomarkers
  • early detection
  • cervical cancer
  • anal cancer
  • oropharyngeal cancer
  • prognostic factors
  • HPV genotyping

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Published Papers (3 papers)

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Research

20 pages, 4171 KB  
Article
Opportunistic and Organized Cervical Cancer Screening: Impact on Lesion Severity and Surgical Outcomes in 9830 Cervical Conizations
by Mario Preti, Niccolò Gallio, Silvano Costa, Fulvio Borella, Paola Armaroli, Pedro Vieira-Baptista, Federica Zamagni, Federica Bevilacqua, Paola Garutti, Daniele Tota, Eleonora Robba, Ilaria Barbierato, Benedetta Pollano, Samuel Joseph Gardner-Medwin, Sara Babich, Camilla Cavallero, Ilaria Maschio, Alessio Mastrippolito, Alberto Revelli, Luca Marozio and Lauro Bucchiadd Show full author list remove Hide full author list
Diagnostics 2026, 16(6), 839; https://doi.org/10.3390/diagnostics16060839 - 12 Mar 2026
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Abstract
Objectives: To assess the impact of organized (OgS) versus opportunistic screening (OpS) on grade, extent, and surgical management of cervical lesions, and to evaluate human papillomavirus (HPV)-based versus cytology-based screening within OgS. Methods: This retrospective study analyzed 9830 women undergoing conization [...] Read more.
Objectives: To assess the impact of organized (OgS) versus opportunistic screening (OpS) on grade, extent, and surgical management of cervical lesions, and to evaluate human papillomavirus (HPV)-based versus cytology-based screening within OgS. Methods: This retrospective study analyzed 9830 women undergoing conization (1992–2021). Data included screening modality, histology, cervical intraepithelial neoplasia grade 3 (CIN3) linear extension, and cone volume. Statistical analysis employed chi-square test, Student’s t-tests, Cochran–Armitage test for trend, and Firth’s penalized multivariate logistic regression to identify independent predictors of invasive disease. Results: Of 9830 patients, 5097 (52%) were referred from OgS and 4733 (48%) from OpS. OgS patients were significantly older (40.0 vs. 37.0 years; p < 0.001). In the final decade, OgS achieved a significantly lower rate of invasive carcinomas compared to OpS (1.1% vs. 2.7%; p < 0.001). Mean CIN3 extension and cone volume were significantly lower in OgS (6.5 mm; 1150 mm3) than in OpS (7.1 mm; 1580 mm3; p < 0.001). Within OgS, HPV-detected CIN3 lesions were smaller than cytology-detected ones (5.9 vs. 6.4 mm; p < 0.001). Long-term analysis showed a borderline downward trend in invasive cancer for OgS (p = 0.089), whereas OpS remained stable at higher risk levels. Multivariate analysis confirmed the screening model as an independent predictor of invasiveness: OpS was associated with a two-fold increased risk of invasive cancer compared to OgS (adjusted odds ratio: 1.99; 95% confidence interval: 1.41–2.83; p < 0.001). Conclusions: OgS identifies high-grade precancers earlier and with smaller excisional requirements. OpS is associated with significantly higher invasive cancer rates and larger conizations. Multivariate data reinforce OgS as a superior framework, effectively halving the risk of invasive disease compared to OpS. Full article
(This article belongs to the Special Issue Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers)
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13 pages, 3450 KB  
Article
ROMO1 as a Diagnostic Biomarker in Cervical Neoplasia: Evidence from Normal, Pre-Invasive, and Invasive Lesions
by Eva Tsoneva, Polina Damyanova, Metodi V. Metodiev, Velizar Shivarov, Mariela Vasileva-Slaveva, Zornitsa Gorcheva, Yonka Ivanova, Yavor Kornovski, Stoyan Kostov, Stanislav Slavchev, Margarita Nikolova, Angel Yordanov and Rafał Watrowski
Diagnostics 2026, 16(1), 24; https://doi.org/10.3390/diagnostics16010024 - 21 Dec 2025
Cited by 1 | Viewed by 592
Abstract
Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of [...] Read more.
Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of cervical cancer are caused by persistent infection with oncogenic high-risk human papillomavirus (HPV). This malignancy usually exhibits a gradual development through well-defined precursor stages, known as cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3, before evolving into invasive carcinoma. In diagnostic practice, several biomarkers have been implemented to improve the detection of high-risk cervical lesions. p16 and Ki-67 greatly aid in identifying HPV-driven dysplasia, but they cannot always reliably distinguish progressive lesions from regressive or transient HPV infections. These limitations highlight the need for novel biomarkers with better predictive accuracy to complement current screening and diagnostic algorithms. ROMO1 has become a possible marker of a high-ROS, high-risk tumor phenotype in a number of cancers. Although oxidative stress, HPV, and cervical carcinogenesis have been linked, nothing is known about ROMO1’s involvement in cervical neoplasia. There is currently a lack of thorough information regarding the expression of ROMO1 in normal vs. precancerous lesions and in cervical cancer, as well as on whether or not its expression is correlated with the severity of the disease. In order to define ROMO1 expression throughout the course of cervical squamous neoplastic development, the current study was created. Methods: We performed immunohistochemical analysis of ROMO1 expression on cervical tissue samples from three groups: healthy cervix (n = 30), cervical intraepithelial neoplasia (CIN) (n = 41), and invasive cervical carcinoma (n = 205). ROMO1 expression in invasive carcinoma was evaluated using an H-score scale. Results: ROMO1 expression was basal in all normal cervix samples (0/30 cases). In contrast, CIN lesions showed 100% ROMO1 expression in the suprabasal layers of abnormal cells in all CIN cases. In invasive cervical carcinomas, ROMO1 expression was heterogeneous. In our cancer cohort (n = 205), ROMO1 H-score showed no significant association with the following: FIGO stage I vs. II vs. III (p = 0.25); histologic grade G1 vs. G2 vs. G3 (p = 0.46); lymphovascular invasion (no vs. yes; p = 0.80); nodal status N0 vs. N1 (p = 0.67); patient age (≤50 y vs. >50 y; p = 0.38). However, ROMO1 expression did vary by histologic subtype (AC vs. ASC vs. SCC; p = 0.02), with SCC enriched for strong staining compared to AC/ASC. With regard to tumor stage (pT stage), pT2a tumors exhibited significantly lower ROMO1 (pT1b1–pT2b; p = 0.035) than pT1b1 (p = 0.04). No other clinicopathologic variable remained significant. Notably, ROMO1 expression was highest in stage I tumors and declined in more advanced stages of cervical carcinoma. Conclusions: These results show a clear pattern of ROMO1 expression across the cervical neoplasia spectrum: it is attenuated in invasive tumors (with a peak in early-stage illness), significantly raised in pre-cancerous CIN lesions, and negligible in normal epithelium. The idea that oxidative stress may be the primary cause of early malignant transformation in the cervix is supported by the noticeable overexpression of ROMO1 in early lesions. For the detection of early-stage cervical carcinoma and high-grade precancerous lesions, ROMO1 may be a useful auxiliary biomarker. Full article
(This article belongs to the Special Issue Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers)
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15 pages, 1983 KB  
Article
Screening for Cervical Cancer and Early Treatment (SCCET) Project—The Programmatic Data of Romanian Experience in Primary Screening for High-Risk HPV DNA
by Gabriel Marian Saveliev, Adriana Irina Ciuvică, Dragos Cretoiu, Valentin Nicolae Varlas, Cristian Balalau, Irina Balescu, Nicolae Bacalbasa, Laurentiu Camil Bohiltea and Nicolae Suciu
Diagnostics 2025, 15(16), 2066; https://doi.org/10.3390/diagnostics15162066 - 18 Aug 2025
Cited by 1 | Viewed by 2142
Abstract
Background/Objectives: Cervical cancer (CC), caused mainly by high-risk human papillomavirus (hrHPV), remains a global health challenge despite being preventable. The disease’s incidence and mortality rates significantly vary across regions, highlighting the need for effective screening programs. The World Health Organization prioritizes CC screening [...] Read more.
Background/Objectives: Cervical cancer (CC), caused mainly by high-risk human papillomavirus (hrHPV), remains a global health challenge despite being preventable. The disease’s incidence and mortality rates significantly vary across regions, highlighting the need for effective screening programs. The World Health Organization prioritizes CC screening to monitor and eliminate the disease. The Screening for Cervical Cancer and Early Treatment (SCCET) project aligns with this goal by adhering to the 2012 National Program for Cervical Cancer Screening and implementing the European Guidelines of Quality Assurance. Methods: The SCCET initiative facilitates access to equitable and high-quality preventive medical services for Romanian women, incorporating the Babeș–Papanicolaou smear (Pap test) and/or hrHPV DNA screening. Focused on the Muntenia Region of South Romania, the project leverages a methodical approach to gather substantial medical data on hrHPV infection rates and cervical lesions, thereby improving health management for women in the screening program. Results: Through public information and educational campaigns about HPV and its link to CC, the SCCET project has significantly enhanced participation in the screening program. In the study conducted between September 2022 and March 2023, 14,385 women aged 30 to 64 years voluntarily participated; of these, 11,996 (83.4%) underwent primary hrHPV DNA screening and were tested using the PowerGene 9600 Plus Real-Time polymerase chain reaction (PCR) system and the commercial Atila BioSystems AmpFire® HPV Screening 16/18/HR test, version 4.1. This substantial participation indicates a positive shift in public attitudes towards CC prevention and highlights the success of the project’s outreach efforts. The study revealed an overall prevalence of hrHPV infection of 12.24%; of these, the most common genotype was other hrHPV types (9.84%), followed by HPV 16 (2.3%) and HPV 18 (0.71%). Conclusions: The SCCET project’s recent data on primary hrHPV DNA screening showcases its pivotal role in advancing the management and prevention of CC in Romania. By providing accessible, high-quality screening services and fostering public education on HPV, the initiative has made significant strides toward reducing the burden of CC. This effort aligns with global public health goals, and providing updated information on the prevalence of hrHPV types will allow the development of personalized national screening and vaccination programs to eradicate CC. Full article
(This article belongs to the Special Issue Pathogenesis and Early Diagnosis of HPV-Related Cancers and Pre-Cancers)
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