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Viruses
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Human and Animal Papillomavirus: Infections, Genetics, and Vaccines
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Human and Animal Papillomavirus: Infections, Genetics, and Vaccines

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

Deadline for manuscript submissions: 10 September 2025 | Viewed by 9160

Special Issue Editors

Dr. Antonio Carlos de Freitas

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Guest Editor
Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Recife, Brazil
Interests: nucleic acid vaccine; yeast-based vaccines; application of immunoinformatics in novel vaccine design; development and evaluation of HPV therapeutic; vaccine Zika; viral pathogenesis; Vaccine delivery
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcus Vinícius de Aragão Batista

E-Mail Website
Guest Editor
Laboratory of Molecular Genetics and Biotechnology, Department of Biology, Federal University of Sergipe, São Cristóvão 49100-000, Brazil
Interests: application of bioinformatics; bovine and human papillomavirus; molecular epidemiology; vaccines
Prof. Dr. Maria Angélica Ramos da Silva

E-Mail Website
Guest Editor
Federal Institute of Paraíba, Paraíba, Brazil
Interests: bovine and human papillomavirus; molecular epidemiology; oncogenesis; infection biology

Special Issue Information

Dear Colleagues,

Papillomavirus (PV) induces exophytic lesions (papillomas, warts) and flat lesions (flat warts, cervical intraepithelial neoplasia) in cutaneous and mucosal epithelia. The lesions are usually benign and generally regress without eliciting severe clinical problems in the host, but occasionally persist. Persistent lesions can be debilitating and can also provide a focus for malignant transformation, particularly in the presence of environmental or genetic cofactors. Human PV (HPV) encompasses over 200 sequenced, characterized, and cataloged types. In contrast to HPV, Bos taurus papillomavirus (BPV) comprises only a few dozen.

For this Special Issue, we hope experts present exciting advances related to papillomavirus genetics and molecular epidemiology, infection biology, and prophylactic and therapeutic vaccine strategies.

Dr. Antonio Carlos de Freitas
Prof. Dr. Marcus Vinícius de Aragão Batista
Prof. Dr. Maria Angélica Ramos da Silva
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

  • vaccines
  • infection biology
  • genetics
  • molecular epidemiology
  • bioinformatics
  • oncogenesis
  • HPV and nongenital cancer
  • HPV and cancer
  • animal papillomavirus and associated diseases

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Published Papers (7 papers)

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22 pages, 3635 KiB  
Article
Human Papillomavirus Type 16 Stimulates WAVE1- and WAVE2-Dependent Actin Protrusions for Endocytic Entry
by Daniel J. Fernandez, Stephanie Cheng, Ruben Prins, Sarah F. Hamm-Alvarez and W. Martin Kast
Viruses 2025, 17(4), 542; https://doi.org/10.3390/v17040542 - 8 Apr 2025
Viewed by 402
Abstract
Human papillomavirus type 16 (HPV16) is an etiological agent of human cancers that requires endocytosis to initiate infection. HPV16 entry into epithelial cells occurs through a non-canonical endocytic pathway that is actin-driven, but it is not well understood how HPV16–cell surface interactions trigger [...] Read more.
Human papillomavirus type 16 (HPV16) is an etiological agent of human cancers that requires endocytosis to initiate infection. HPV16 entry into epithelial cells occurs through a non-canonical endocytic pathway that is actin-driven, but it is not well understood how HPV16–cell surface interactions trigger actin reorganization in a way that facilitates entry. This study provides evidence that Wiskott–Aldrich syndrome protein family verprolin-homologous proteins 1 and 2 (WAVE1 and WAVE2) are molecular mediators of actin protrusions that occur at the cellular surface upon HPV addition to cells, and that this stimulation is a key step prior to endocytosis and intracellular trafficking. We demonstrate through post-transcriptional gene silencing and genome editing that WAVE1 and WAVE2 are critical for efficient HPV16 infection, and that restoration of each in knockout cells rescues HPV16 infection. Cells lacking WAVE1, WAVE2, or both internalize HPV16 at a significantly reduced rate. Microscopic analysis of fluorescently labeled cells revealed that HPV16, WAVE1, WAVE2, and actin are all colocalized at the cellular dorsal surface within a timeframe that precedes endocytosis. Within that same timeframe, we also found that HPV16-treated cells express cellular dorsal surface filopodia, which does not occur in cells lacking WAVE1 and WAVE2. Taken together, this study provides evidence that WAVE1 and WAVE2 mediate a key step prior to HPV entry into cells that involves actin reorganization in the form of cellular dorsal surface protrusions. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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11 pages, 1143 KiB  
Article
Assessment of Relative Contributions of Lifestyle, Behavioral and Biological Risk Factors for Cervical Human Papillomavirus Infections in Female Sex Workers
by Imran Morhason-Bello, Kyeezu Kim, Yusuf Bello, Yinan Zheng, Sunday Oyerinde, Oluwasegun Caleb Idowu, Miquel Ángel Pavón, Kathy Baisley, Jun Wang, Adeola Fowotade, Mamoudou Maiga, Musa Jonah, Elizabeth Nicole Christian, Olufemi Ogunbiyi, Isaac Adewole, Lifang Hou, Suzanna C. Francis and Deborah Watson-Jones
Viruses 2025, 17(4), 485; https://doi.org/10.3390/v17040485 - 28 Mar 2025
Viewed by 522
Abstract
This study aimed to identify and quantify the relative and collective contributions of lifestyle, behavioral, and biological risk factors to cervical HPV infections among female sex workers (FSWs) in Ibadan, Nigeria. This cross-sectional study was part of the Sexual Behavior and HPV Infections [...] Read more.
This study aimed to identify and quantify the relative and collective contributions of lifestyle, behavioral, and biological risk factors to cervical HPV infections among female sex workers (FSWs) in Ibadan, Nigeria. This cross-sectional study was part of the Sexual Behavior and HPV Infections in Nigerians in Ibadan project and involved 182 FSWs for whom complete data on HPV genotypes were available. Quantile-based g-computation was employed to assess the relative and collective contributions of risk factors to any cervical HPV/hrHPV infections and multiple cervical HPV/hrHPV. The collective contribution of all selected risk factors to multiple high-risk cervical HPV was 2.47 (95% CI: 0.97–3.23). The number of other anatomic sites with HPV infections showed the highest positive relative contribution to multiple cervical HPV/hrHPV. Alcohol consumption and the total number of sexual partners contributed to high-risk cervical HPV and multiple cervical HPV/hrHPV, while age at first vaginal sex had a negative relative contribution. This study highlights the significant contribution of HPV infections in multiple anatomic sites as a risk to the acquisition of cervical HPV in FSWs. Routine screening protocols should be enhanced to include multiple anatomic sites, and targeted educational programs are recommended to address the specific risks faced by FSWs. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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21 pages, 1854 KiB  
Article
Therapeutic Impact of Gardasil® in Recurrent Respiratory Papillomatosis: A Retrospective Study on RRP Patients
by Jennifer Sieg, Asita Fazel, Elgar Susanne Quabius, Astrid Dempfle, Susanne Wiegand and Markus Hoffmann
Viruses 2025, 17(3), 321; https://doi.org/10.3390/v17030321 - 26 Feb 2025
Viewed by 782
Abstract
Background: Recurrent respiratory papillomatosis (RRP) is a rare, non-malignant disease caused by human papillomavirus (HPV) types 6 and 11. The condition primarily affects the larynx, potentially leading to life-threatening airway obstruction. It is more aggressive in younger patients, necessitating frequent surgical interventions. This [...] Read more.
Background: Recurrent respiratory papillomatosis (RRP) is a rare, non-malignant disease caused by human papillomavirus (HPV) types 6 and 11. The condition primarily affects the larynx, potentially leading to life-threatening airway obstruction. It is more aggressive in younger patients, necessitating frequent surgical interventions. This study investigates the therapeutic potential of the prophylactic HPV vaccine Gardasil® in RRP patients, focusing on its impact on lesion size and the frequency of surgical interventions. Furthermore, a literature review was conducted to analyze the factors influencing the decision to vaccinate. Methods: A retrospective analysis was conducted on 63 RRP patients treated from 2008 to 2021. Disease burden was assessed using the Derkay score and the annual frequency of laser-surgical ablations. Comparisons were made between pre- and post-vaccination periods in vaccinated patients (n = 18), and between first and second halves of the disease’s course in unvaccinated patients (n = 14). Results: A reduction in the frequency of surgical interventions post-vaccination (p < 0.05) could be seen. The cumulated Derkay score per year decreased after second and third vaccination (p < 0.05). The decision to be vaccinated is influenced by multiple factors (e.g., potential side-effects, sociocultural factors, impact of social media, pre-existing conditions and the wider context of the recent pandemic). Conclusions: Gardasil® appears to reduce the frequency of surgery and lessen disease severity in RRP patients, supporting the potential role of HPV vaccination as a therapeutic option for RRP. Moreover, it is crucial to overcome skepticism towards vaccinations to prevent the development of HPV-associated diseases in the first place. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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15 pages, 3086 KiB  
Article
Immune Response Modulation by HPV16 Oncoproteins in Lung Cancer: Insights from Clinical and In Vitro Investigations
by Bianca de França São Marcos, Daffany Luana dos Santos, Georon Ferreira de Sousa, Leonardo Carvalho de Oliveira Cruz, Bárbara Rafaela da Silva Barros, Matheus Gardini Amâncio Marques de Sena, Vanessa Emanuelle Pereira Santos, Talita Helena de Araújo Oliveira, Cristiane Moutinho Lagos de Melo and Antonio Carlos de Freitas
Viruses 2024, 16(11), 1731; https://doi.org/10.3390/v16111731 - 4 Nov 2024
Viewed by 1388
Abstract
Lung cancer has the highest mortality rates worldwide, and Human Papillomavirus (HPV) has been associated with its carcinogenesis. In this study, HPV16 genes’ expressions were investigated in patient samples, along with the immunological response promoted by lymphocytes and monocytes in A549 cells transfected [...] Read more.
Lung cancer has the highest mortality rates worldwide, and Human Papillomavirus (HPV) has been associated with its carcinogenesis. In this study, HPV16 genes’ expressions were investigated in patient samples, along with the immunological response promoted by lymphocytes and monocytes in A549 cells transfected with HPV oncogenes and co-cultured with PBMC. An increase in the expression of E5 was observed in the patients’ samples. In the in vitro analysis, a decrease in the number of monocytes and cytotoxic cells was observed when co-stimulated by E6 and E7, and it promoted an increase in the Th2 profile. In contrast, the high proliferation of cytotoxic cells in A549 cells transfected with E5, associated with the high expression of costimulatory molecules in monocytes, suggests a low capacity of E5 to inhibit the presentation of antigens by antigen-presenting cells (APC) and a possible use of E5 in future therapeutic strategies against lung cancers associated with HPV. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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10 pages, 570 KiB  
Article
Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women
by Ena Pešut, Ivana Šimić, Rajko Fureš, Nina Milutin Gašperov, Cvjetko Lež, Fabijan Feratović, Tomica Kukina Žvigač, Magdalena Grce, Ivana Erceg Ivkošić and Ivan Sabol
Viruses 2024, 16(4), 642; https://doi.org/10.3390/v16040642 - 20 Apr 2024
Cited by 2 | Viewed by 1857
Abstract
The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV [...] Read more.
The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999–2015) and post-vaccination periods (2020–2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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9 pages, 2663 KiB  
Case Report
Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency
by Assiya El Kettani, Hind Ouair, Farida Marnissi, Jalila El Bakkouri, Rémi Chevalier, Lazaro Lorenzo, Halima Kholaiq, Vivien Béziat, Emmanuelle Jouanguy, Jean-Laurent Casanova and Ahmed Aziz Bousfiha
Viruses 2024, 16(9), 1415; https://doi.org/10.3390/v16091415 - 5 Sep 2024
Viewed by 1431
Abstract
Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from two [...] Read more.
Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from two independent families, with syndromic EV for both of them. By whole exome sequencing, we found that the patients carry new homozygous variants in STK4, both leading to a premature stop codon. STK4 deficiency causes a combined immunodeficiency characterized by a broad infectious susceptibility to bacteria, viruses, and fungi. Auto-immune manifestations were also reported. Deep immunophenotyping revealed multiple cytopenia in the three affected patients, in particular deep CD4+ T cells deficiency. We report here the fourth and the fifth cases of the syndromic EV due to STK4 deficiency. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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11 pages, 805 KiB  
Perspective
Update on Effects of the Prophylactic HPV Vaccines on HPV Type Prevalence and Cervical Pathology
by Ian N. Hampson and Anthony W. Oliver
Viruses 2024, 16(8), 1245; https://doi.org/10.3390/v16081245 - 2 Aug 2024
Cited by 3 | Viewed by 1942
Abstract
Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have [...] Read more.
Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location—presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices. Full article
(This article belongs to the Special Issue Human and Animal Papillomavirus: Infections, Genetics, and Vaccines)
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