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Viruses
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HPV-Associated Cancers
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HPV-Associated Cancers

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 12100

Special Issue Editors

Prof. Dr. Rui Medeiros

E-Mail Website
Guest Editor
Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal
Interests: HPV; cervical cancer; microrna; cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hugo Sousa

E-Mail Website
Guest Editor
Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal
Interests: human papillomavirus; herpesvirus; epstein-barr virus; genetic susceptibility; cervical cancer; nasopharyngeal carcinoma; head and neck cancer; gastric cancer

Special Issue Information

Dear Colleagues,

Approximately 10% of worldwide cancers may be attributable to viral infection, which strongly impact the survival and quality of life of affected individuals. Since the identification and characterization of human papillomaviruses (HPVs), an enormous amount of knowledge has been acquired for better understanding the HPV-related disease burden and its associated risk factors, prevention strategies, screening activities, and the onset of immunization programs/vaccination. We must consider that viral diseases, as in the case of HPV, are the result of “pathogen–host–environment” interaction. Epidemiology, diagnosis and treatment studies are critical to the elucidation of the complexity of viral diseases and develop efficient prevention strategies. Cervical cancer is the most studied cancer linked to HPV, but the new trends in research indicate the role of HPV in other cancers as in the case of head and neck and penile cancer. Furthermore, it seems that in the case of head and neck cancer, we must consider HPV not only as a putative etiologic factor in part of the cases, but also as a biomarker of a different biologic behaviour, particularly linked to a better response to therapy compared to non-HPV-associated cancer. Moreover, research has underlined that we must consider HPV in its interaction with the genetic background, epigenetics and tissue environment.

The aim of this Special Issue is to consider the social and public health impact of these diseases and foster discussion and knowledge in the field. The hope is that this Special Issue can contribute to the development of efficient prevention strategies against HPV-associated cancers or better treatment of patients and in accordance with the World Health Assembly’s adopted global strategy to accelerate cervical cancer elimination and other HPV-associated cancers.

Prof. Dr. Rui Medeiros
Prof. Dr. Hugo Sousa
Guest Editors

Manuscript Submission Information

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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 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
  • cervical cancer
  • head and neck cancer
  • penile cancer
  • cancer prevention
  • targeted therapy
  • cancer stem cells
  • molecular study
  • carcinogenesis
  • immunotherapy

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Published Papers (7 papers)

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Research

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13 pages, 970 KiB  
Article
Identification of HPV16 Lineages in South African and Mozambican Women with Normal and Abnormal Cervical Cytology
by Cremildo Maueia, Olivia Carulei, Alltalents T. Murahwa, Ongeziwe Taku, Alice Manjate, Tufária Mussá and Anna-Lise Williamson
Viruses 2024, 16(8), 1314; https://doi.org/10.3390/v16081314 - 18 Aug 2024
Viewed by 933
Abstract
Background: Human papillomavirus 16 (HPV16) is an oncogenic virus responsible for the majority of invasive cervical cancer cases worldwide. Due to genetic modifications, some variants are more oncogenic than others. We analysed the HPV16 phylogeny in HPV16-positive cervical Desoxyribonucleic Acid (DNA) samples collected [...] Read more.
Background: Human papillomavirus 16 (HPV16) is an oncogenic virus responsible for the majority of invasive cervical cancer cases worldwide. Due to genetic modifications, some variants are more oncogenic than others. We analysed the HPV16 phylogeny in HPV16-positive cervical Desoxyribonucleic Acid (DNA) samples collected from South African and Mozambican women to detect the circulating lineages. Methods: Polymerase chain reaction (PCR) amplification of the long control region (LCR) and 300 nucleotides of the E6 region was performed using HPV16-specific primers on HPV16-positive cervical samples collected in women from South Africa and Mozambique. HPV16 sequences were obtained through Next Generation Sequencing (NGS) methods. Geneious prime and MEGA 11 software were used to align the sequences to 16 HPV16 reference sequences, gathering the A, B, C, and D lineages and generating the phylogenetic tree. Single nucleotide polymorphisms (SNPs) in the LCR and E6 regions were analysed and the phylogenetic tree was generated using Geneious Prime software. Results: Fifty-eight sequences were analysed. Of these sequences, 79% (46/58) were from women who had abnormal cervical cytology. Fifteen SNPs in the LCR and eight in the E6 region were found to be the most common in all sequences. The phylogenetic analysis determined that 45% of the isolates belonged to the A1 sublineage (European variant), 34% belonged to the C1 sublineage (African 1 variant), 16% belonged to the B1 and B2 sublineage (African 2 variant), two isolates belonged to the D1–3 sublineages (Asian-American variant), and one to the North American variant. Conclusions: The African and European HPV16 variants were the most common circulating lineages in South African and Mozambican women. A high-grade squamous intraepithelial lesion (HSIL) was the most common cervical abnormality observed and linked to European and African lineages. These findings may contribute to understanding molecular HPV16 epidemiology in South Africa and Mozambique. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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13 pages, 2884 KiB  
Article
From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study
by Pei-Ju Wu, Stella Chin-Shaw Tsai, Jing-Yang Huang, Maw-Sheng Lee, Po-Hui Wang and Frank Cheau-Feng Lin
Viruses 2023, 15(12), 2314; https://doi.org/10.3390/v15122314 - 25 Nov 2023
Cited by 2 | Viewed by 1730
Abstract
Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal [...] Read more.
Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335–1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376–2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377–2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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10 pages, 2371 KiB  
Article
Broad-Spectrum Detection of HPV in Male Genital Samples Using Target-Enriched Whole-Genome Sequencing
by Tengguo Li, Elizabeth R. Unger and Mangalathu S. Rajeevan
Viruses 2023, 15(9), 1967; https://doi.org/10.3390/v15091967 - 21 Sep 2023
Viewed by 1325
Abstract
Most human papillomavirus (HPV) surveillance studies target 30–50 of the more than 200 known types. We applied our recently described enriched whole-genome sequencing (eWGS) assay to demonstrate the impact of detecting all known and novel HPV types in male genital samples (n [...] Read more.
Most human papillomavirus (HPV) surveillance studies target 30–50 of the more than 200 known types. We applied our recently described enriched whole-genome sequencing (eWGS) assay to demonstrate the impact of detecting all known and novel HPV types in male genital samples (n = 50). HPV was detected in nearly all (82%) samples, (mean number of types/samples 13.6; range 1–85), and nearly all HPV-positive samples included types in multiple genera (88%). A total of 560 HPV detections (237 unique HPV types: 46 alpha, 55 beta, 135 gamma, and 1 mu types) were made. The most frequently detected HPV types were alpha (HPV90, 43, and 74), beta (HPV115, 195, and 120), and gamma (HPV134, mSD2, and HPV50). High-risk alpha types (HPV16, 18, 31, 39, 52, and 58) were not common. A novel gamma type was identified (now officially HPV229) along with 90 unclassified types. This pilot study demonstrates the utility of the eWGS assay for broad-spectrum type detection and suggests a significantly higher type diversity in males compared to females that warrants further study. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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Review

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17 pages, 974 KiB  
Review
HPV and HCMV in Cervical Cancer: A Review of Their Co-Occurrence in Premalignant and Malignant Lesions
by Rancés Blanco and Juan P. Muñoz
Viruses 2024, 16(11), 1699; https://doi.org/10.3390/v16111699 - 30 Oct 2024
Viewed by 1086
Abstract
Cervical cancer remains a significant global health concern, particularly in low- and middle-income countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human [...] Read more.
Cervical cancer remains a significant global health concern, particularly in low- and middle-income countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human cytomegalovirus (HCMV) is a widespread β-herpesvirus known for its ability to establish lifelong latency and reactivate under certain conditions, often contributing to chronic inflammation and immune modulation. Emerging evidence suggests that HCMV may play a role in various cancers, including cervical cancer, through its potential to influence oncogenic pathways and disrupt host immune responses. This review explores clinical evidence regarding the co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer. The literature reviewed indicates that HCMV is frequently detected in cervical lesions, particularly in those co-infected with HPV, suggesting a potential synergistic interaction that could enhance HPV’s oncogenic effects, thereby facilitating the progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) and invasive cancer. Although the precise molecular mechanisms were not thoroughly investigated in this review, the clinical evidence suggests the importance of considering HCMV alongside HPV in the management of cervical lesions. A better understanding of the interaction between HR-HPV and HCMV may lead to improved diagnostic, therapeutic, and preventive strategies for cervical cancer. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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22 pages, 391 KiB  
Review
HPV and Cervical Cancer: Molecular and Immunological Aspects, Epidemiology and Effect of Vaccination in Latin American Women
by Christian David Hernández-Silva, Adrián Ramírez de Arellano, Ana Laura Pereira-Suárez and Inocencia Guadalupe Ramírez-López
Viruses 2024, 16(3), 327; https://doi.org/10.3390/v16030327 - 21 Feb 2024
Cited by 3 | Viewed by 2692
Abstract
Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores [...] Read more.
Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores molecular and immunological aspects of HPV infection, its role in cervical cancer development, and the epidemiology in this region, highlighting the prevalence and diversity of HPV genotypes. The impact of vaccination initiatives on cervical cancer rates in Latin America is critically evaluated. The advent of HPV vaccines has presented a significant tool in combating the burden of this malignancy, with notable successes observed in various countries, the latter due to their impact on immune responses. The review synthesizes current knowledge, emphasizes the importance of continued research and strategies for cervical cancer prevention, and underscores the need for ongoing efforts in this field. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
25 pages, 2536 KiB  
Review
Comparative Analysis of Alpha and Beta HPV E6 Oncoproteins: Insights into Functional Distinctions and Divergent Mechanisms of Pathogenesis
by Josipa Skelin and Vjekoslav Tomaić
Viruses 2023, 15(11), 2253; https://doi.org/10.3390/v15112253 - 14 Nov 2023
Cited by 1 | Viewed by 2477
Abstract
Human papillomaviruses (HPVs) represent a diverse group of DNA viruses that infect epithelial cells of mucosal and cutaneous tissues, leading to a wide spectrum of clinical outcomes. Among various HPVs, alpha (α) and beta (β) types have garnered significant attention due to their [...] Read more.
Human papillomaviruses (HPVs) represent a diverse group of DNA viruses that infect epithelial cells of mucosal and cutaneous tissues, leading to a wide spectrum of clinical outcomes. Among various HPVs, alpha (α) and beta (β) types have garnered significant attention due to their associations with human health. α-HPVs are primarily linked to infections of the mucosa, with high-risk subtypes, such as HPV16 and HPV18, being the major etiological agents of cervical and oropharyngeal cancers. In contrast, β-HPVs are predominantly associated with cutaneous infections and are commonly found on healthy skin. However, certain β-types, notably HPV5 and HPV8, have been implicated in the development of non-melanoma skin cancers in immunocompromised individuals, highlighting their potential role in pathogenicity. In this review, we comprehensively analyze the similarities and differences between α- and β-HPV E6 oncoproteins, one of the major drivers of viral replication and cellular transformation, and how these impact viral fitness and the capacity to induce malignancy. In particular, we compare the mechanisms these oncoproteins use to modulate common cellular processes—apoptosis, DNA damage repair, cell differentiation, and the immune response—further shedding light on their shared and distinct features, which enable them to replicate at divergent locations of the human body and cause different types of cancer. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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Other

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5 pages, 869 KiB  
Brief Report
The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region
by Tiziana Pisani, Ettore Domenico Capoluongo and Maria Cenci
Viruses 2024, 16(7), 1149; https://doi.org/10.3390/v16071149 - 17 Jul 2024
Viewed by 809
Abstract
Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation [...] Read more.
Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices. Full article
(This article belongs to the Special Issue HPV-Associated Cancers)
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