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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 17498

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Special Issue Editor

Prof. Dr. Beata Biesaga

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Guest Editor

Maria Skłodowska-Curie National Research Institute of Oncology, Cracow Branch, Cracow, Poland
Interests: HPV infections; cancer
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Dear Colleagues,

Currently, infection with high-risk human papillomavirus (HR-HPV) is estimated to be the primary etiological factor for approximately 5% of all malignant tumors. HR-HPV infection is a well-established risk factor in the development of certain anogenital cancers, including cervical, vulvar, penile, and anal cancers. Recently, increasing attention has been directed toward the role of this infection in the development of other types of malignant tumors. Understanding the prevalence of HPV infection across various malignant tumor types may enhance our comprehension of the carcinogenesis process and assist in identifying novel prognostic and/or predictive factors in non-anogenital cancers. Although HPV infection is a recognized risk factor in the aforementioned cancers, its significance in the development of many other malignant tumors remains under investigation. Additionally, methods for detecting transcriptionally active infection, in particular, require further research. Therefore, we warmly invite you to submit your publication to the Special Issue of Cancers entitled “Human Papillomavirus (HPV) and Related Cancer”.

Prof. Dr. Beata Biesaga
Guest Editor

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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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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Keywords

HPV
carcinogenesis
methods of virus identification diagnostics
prognostification

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Published Papers (7 papers)

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Research

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17 pages, 1721 KB

Open AccessArticle

Informative High-Risk HPV Genotyping in Cervical Cancer Screening: Integrated Analysis of Cytology and p16/Ki67 Dual Staining

by Martyna Trzeszcz, Karolina Mazurec, Maciej Mazurec, Christopher Kobierzycki, Agnieszka Halon and Robert Jach

Cancers 2026, 18(7), 1056; https://doi.org/10.3390/cancers18071056 - 25 Mar 2026

Viewed by 460

Abstract

Background/Objectives: The informative value of integrating high-risk human papillomavirus (HR-HPV) genotyping with cytology and p16/Ki67 dual-stain biomarker results, using limited and two types of extended genotyping assays, has not yet been evaluated. Methods: A total of 32,724 screening test results between 2015 and 2024 were included. Limited HPV genotyping was performed using the Abbott RealTime High Risk HPV assay. Extended genotyping was performed using two assays: the Alinity m HR HPV and BD Onclarity HPV Assay. Trends in age-specific, cytology-specific, and p16/Ki67-specific HR-HPV prevalence and distribution were observed, and differences between limited and extended genotyping were examined. Results: The overall HR-HPV positivity rate was 15.0%. HR-HPV prevalence was 13.9% in the limited genotyping group, 17.8% in in the Onclarity group 1, and 17.2% in the Alinity group 2, with a statistically significant difference in the proportions of positive/negative cases (p < 0.0001). No statistically significant difference was observed between extended genotyping groups (p = 0.706). In the Onclarity group: the highest p16/Ki67 positivity was observed for HPV 33/58 (100.0%) and HPV 31 (58.8%), while the lowest was for HPV 45 (18.2%), HPV 18 (25.0%) and HPV 59/56/66 (28.9%). In the Alinity group: the highest p16/Ki67 positivity was observed for HPV 16 (66.7%) and HPV 31/33/52/58 (58.8%). Conclusions: Based on ten years of HPV-based cervical cancer screening data, this study demonstrates that genotype-specific HR-HPV information obtained through extended genotyping provides clinically relevant risk stratification when interpreted together with cytology and p16/Ki67 dual-stain results. These findings support an integrated screening approach combining molecular HPV testing, cytology, and immunocytochemical biomarkers to improve risk-based triage in cervical cancer screening. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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12 pages, 241 KB

Open AccessArticle

Association of TLR-4 and TLR-9 Polymorphisms with HPV Infection and Cervical Dysplasia in Hispanic Women

by Keimari Mendez, Ana Rosario-Santos, Magaly Martínez-Ferrer, Naydi Pérez-Rios, Alejandro O. Rivera-Torres, Josefina Romaguera and Filipa Godoy-Vitorino

Cancers 2025, 17(23), 3795; https://doi.org/10.3390/cancers17233795 - 27 Nov 2025

Viewed by 1124

Abstract

Background/Objective: Cervical cancer incidence is rising in Puerto Rico (PR) despite being preventable through HPV vaccination, Pap smear screening, and the timely treatment of dysplasia. This study evaluated the presence of single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLR4 and TLR9) among women with cervical dysplasia and HPV infection, as potential immune-related susceptibility factors. Methods: Cervicovaginal samples from 210 Hispanic women in PR were analyzed for dysplasia severity and HPV genotype. Demographic data were collected. Seven SNPs (four in TLR4, three in TLR9) were examined using PCR-RFLP and AS-PCR. Associations between SNP frequency, dysplasia severity, and high-risk HPV (HR-HPV) were assessed. Results: HR-HPV was found in 64% of severe dysplasia cases versus 46% of mild/negative cases (p < 0.025). The TLR4 AG (rs4986790) and CT (rs1927911) genotypes were more frequent in severe dysplasia. For TLR9, CT heterozygotes (rs187084) and the TC genotype (rs5743836) were also enriched in severe dysplasia. Conclusions: This first PR-based study shows that TLR4 and TLR9 SNPs significantly correlate with HR-HPV infection and dysplasia severity, supporting further research on their potential as biomarkers for cervical cancer prevention. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

12 pages, 707 KB

Open AccessArticle

Discordance Between p16-Expression and HPV-Status in Sinonasal Carcinoma: A Multicenter Retrospective Study

by Nina Wenda, Henrike Barbara Zech, Marta Barde, Leoni Ramke, Anna Sophie Hoffmann, Till Clauditz, Sebastian Wagner, Jan Gosepath and Christian Stephan Betz

Cancers 2025, 17(19), 3135; https://doi.org/10.3390/cancers17193135 - 26 Sep 2025

Cited by 2 | Viewed by 1240

Abstract

Background/Objectives: Human papillomavirus (HPV) infection is a well-established risk factor for oropharyngeal squamous cell carcinoma (OPSCC), where p16 immunohistochemistry serves as a surrogate marker. However, the role of HPV in sinonasal squamous cell carcinoma (SNSCC) remains less defined, and the reliability of p16 as a standalone surrogate is under debate. This study aimed to assess the concordance between p16 expression and HPV-DNA status in SNSCC and characterize clinicopathologic features in HPV-associated cases. Methods: We retrospectively analyzed 111 SNSCC cases diagnosed between 2008 and 2024 at two German centers. p16 status was determined by immunohistochemistry using site-specific antibody protocols. HPV-DNA testing and genotyping were performed via PCR and reverse hybridization. Clinical and histopathological data were collected and compared between HPV-positive and -negative tumors. Results: HPV-DNA was detected in 31/111 cases (27.9%), with HPV16 and HPV33 (Site A) and HPV 16 and HPV18 (Site B) being the most frequent subtypes. Discordance between p16 and HPV-DNA status was observed in 29.7% of cases, with site-specific discordance rates of 44.6% and 14.5%. Patients with HPV-positive tumors were younger than their HPV-negative counterparts. Conclusions: Our findings underscore the limitations of p16 as a single surrogate marker for detecting HPV-associated sinonasal cancer. Future research on the role of HPV in sinonasal cancer should integrate complementary testing methods (like p16Ink4A immunohistochemistry and HPV DNA/mRNA analysis) and aim for test standardization. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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Review

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29 pages, 3271 KB

Open AccessReview

Therapeutic Landscape of HPV-Associated Cancers: From Mechanisms and Conventional Approaches to Future Innovations

by Muneera Anwer, Krupa Bhaliya, Memoona Zahra, Urooj Yousaf Virk, Hafiza Aasia Malik and Ming Q. Wei

Cancers 2026, 18(4), 636; https://doi.org/10.3390/cancers18040636 - 15 Feb 2026

Viewed by 880

Abstract

Cancer remains the second leading cause of mortality worldwide. Human papillomavirus is a widespread DNA virus with well-established oncogenic potential, particularly among high-risk genotypes such as HPV16 and HPV18. Persistent infection with these genotypes can lead to the development of several malignancies, including cervical, oropharyngeal, anal, penile, vulvar, and vaginal cancers. Cervical cancer persists as the most prevalent malignancy associated with HPV infection, disproportionately affecting low- and middle-income countries. This review provides an overview of the HPV genome, viral genotypes, and associated malignancies, with particular emphasis on the viral oncoproteins E6 and E7 and the mechanisms of viral DNA integration into the host genome. In addition, recent advances in diagnostic technologies, therapeutic strategies, ongoing clinical trials, and future directions to reduce the global burden of HPV-related cancers are discussed. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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14 pages, 412 KB

Open AccessReview

Neoadjuvant Chemotherapy for Oropharyngeal Cancer Treatment De-Escalation: From Historical Failures to Contemporary HPV-Driven Paradigms

by Alvaro Sanabria, Juan P. Rodrigo, Anna Luíza Damaceno Araújo and Luiz P. Kowalski

Cancers 2026, 18(1), 23; https://doi.org/10.3390/cancers18010023 - 21 Dec 2025

Viewed by 895

Abstract

Background/Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) management has shifted following recognition of HPV-driven disease. Neoadjuvant chemotherapy (NAC) has historically failed to improve overall survival (OS) in mixed head and neck cohorts, although contemporary HPV-stratified series suggest NAC may enable treatment de-escalation. We aimed to narratively synthesize OPSCC-specific evidence on NAC focusing on primary and nodal response, pathologic complete response (pCR), survival, and functional outcomes. Methods: We conducted a narrative review of PubMed, selecting primary studies in which OPSCC outcomes were reported separately (surgery- or chemoradiotherapy [CRT]-based strategies; HPV status when available). We extracted study design, treatment regimens, response outcomes, survival, and toxicity data. Results: Pre-HPV studies showed variable responses and no consistent OS advantage over locoregional therapy. In the HPV era, non-comparative cohorts of NAC followed by transoral surgery reported substantial downstaging and high pCR rates at both the primary site and regional nodes, with 3–5-year OS frequently ≥80%. NAC+CRT paradigms demonstrated high clinical CR rates and OS exceeding 80–90%, and lower feeding-tube dependence and reduced swallowing morbidity in de-escalated regimens. Comparative retrospective series suggest NAC + surgery may be associated with lower rates of distant metastases and feeding-tube use compared with CRT or upfront surgery, although interpretation is limited by selection bias, regimen heterogeneity, and small sample sizes. Conclusions: While randomized trials have not established an OS advantage for NAC over standard CRT in head and neck cancer overall, HPV-positive OPSCC shows emerging evidence that systemic intensification with NAC may enable surgical and/or radiation de-escalation with promising oncologic and functional outcomes. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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21 pages, 616 KB

Open AccessReview

Cervical Cancer Screening in the HPV-Vaccinated and Digital Era: Reassessing Strategies in Light of Artificial Intelligence and Evolving Risk

by Apostolia Galani, Athanasios Zikopoulos, Efthalia Moustakli, Anastasios Potiris, Maria Paraskevaidi, Ioannis Arkoulis, Pavlos Machairoudias, Stefania Maneta Stavrakaki, Maria Kyrgiou and Sofoklis Stavros

Cancers 2025, 17(19), 3179; https://doi.org/10.3390/cancers17193179 - 30 Sep 2025

Cited by 7 | Viewed by 3751

Abstract

Background: The widespread use of the human papillomavirus (HPV) vaccine and the rise in digital technologies like artificial intelligence (AI) are causing significant changes in the paradigms surrounding cervical cancer screening. Objective: This review addresses potential future paths toward risk-based, customized screening and prevention while summarizing the available data on how vaccination and digital innovation are changing cervical cancer screening methods. Results: A shift from cytology-based screening to HPV-based primary testing with longer intervals has been supported by the notable decrease in high-grade cervical lesions brought about by HPV vaccination. However, AI and digital health tools, such as digital colposcopy, automated cytology, telemedicine, and self-sampling, have the potential to increase diagnostic access, accuracy, and efficiency, especially in low-resource environments. Implementation hurdles, data security, and algorithmic bias are major obstacles. Conclusions: Digital platforms, molecular diagnostics, and vaccination histories must all be incorporated into screening methods in order to keep up with the decline in HPV-related illness. The elimination of cervical cancer could be accelerated and equality and efficiency increased with customized, risk-based algorithms. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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18 pages, 4098 KB

Open AccessReview

Human Papillomavirus-Related Cutaneous Squamous Cell Carcinoma

by Alejandra Sandoval-Clavijo, Ignasí Martí-Martí, Carla Ferrándiz-Pulido, Júlia Verdaguer-Faja, Ane Jaka and Agustí Toll

Cancers 2025, 17(5), 897; https://doi.org/10.3390/cancers17050897 - 5 Mar 2025

Cited by 4 | Viewed by 8276

Abstract

The human papillomavirus (HPV) has been associated with the carcinogenesis of cutaneous squamous cell carcinoma (cSCC), especially in immunosuppressed patients. This article reviews the microbiology of HPV and its role in tissue tropism, invasion, and oncogenesis. It also describes possible HPV oncogenic ability due to the inactivation of the host p53 and retinoblastoma protein (pRb) by HPV oncoproteins E6 and E7, producing a suppression of cell cycle checkpoints and uncontrolled cell proliferation that may eventually result in invasive carcinoma. We will focus on β-HPV types and their role in epidermodysplasia verruciformis (EV), as well as α types and their ability to cause cutaneous and mucosal pathology. We also intend to examine the clinical characteristics of cSCC related to HPV and host immunosuppression conditions such as solid organ transplant in order to provide management guidelines for patients with cSCC associated with HPV based on available data. Other topics addressed in this article include particular locations of cSCC, such as nails; the prognosis; the recurrence; therapeutic modalities; and the role of HPV vaccines. Full article

(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)

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