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Recent Research on Human Papillomavirus (HPV) Infection and Vaccination

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Human Papillomavirus Vaccines".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 18822

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Special Issue Editors

Dr. Li Shi

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Guest Editor

Laboratory of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming 650118, China
Interests: major research interests in the immunogenetic basis of susceptibility and resistance to human papilloma virus infection; the application of immunogenetics in novel vaccine design, development and evaluation, such as HPV therapeutic vaccine

Prof. Dr. Yufeng Yao

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Guest Editor

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China
Interests: the interaction of host-HPV in the development of cervical cancer and the HPV therapeutic vaccine

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute a paper for the special edition on “Recent Research on Human Papillomavirus (HPV) Infection and Vaccination”. Persistent infection with high-risk Human papillomavirus is associated with virtually all cervical cancers and a significant proportion of anogenital and oropharyngeal cancers. In recent years, significant progress has been made in cervical cancer prevention, especially in terms of the availability of prophylactic vaccines. However, the HPV vaccine has not yet achieved full coverage, and rates have dropped during the COVID-19 pandemic. It is therefore necessary to strengthen HPV vaccine education, vaccination and early prevention, especially in situations such as in low-income countries, where there are still multiple issues related to its dissemination and acceptance. Meanwhile, exploring the various aspects underlying the mechanism of progression of HPV-associated malignancies, host immune system reactions toward HPV viruses as well as HPV vaccination are important for the development of specific therapeutics and vaccines against viral clinical manifestations.

Original research articles and reviews are welcome in this Special Issue. Research areas may include (but are not limited to) discussing the knowledge and attitudes surrounding prophylactic HPV vaccination; vaccination implementation; effective instruments or interventions to improve public awareness of HPV vaccination; improving equity in HPV vaccination; the impact of the COVID-19 pandemic on HPV vaccination; host factors related to HPV infection, persistent, cervical intraepithelial neoplasia, and cervical cancer; co-infection of HPV with other pathogens; progression of HPV-associated malignancies; HPV and host–virus interaction; novel HPV vaccine development.

We look forward to receiving your contributions.

Dr. Li Shi
Prof. Dr. Yufeng Yao
Guest Editors

Manuscript Submission Information

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Keywords

HPV infection
HPV vaccination
willingness
hesitancy
therapeutic vaccines
cervical cancer prevention

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15 pages, 1634 KiB

Open AccessArticle

Elimination of Human Papillomavirus 16-Positive Tumors by a Mucosal rAd5 Therapeutic Vaccination in a Pre-Clinical Murine Study

by Molly R. Braun, Anne C. Moore, Jonathan D. Lindbloom, Katherine A. Hodgson, Emery G. Dora and Sean N. Tucker

Vaccines 2024, 12(9), 955; https://doi.org/10.3390/vaccines12090955 - 23 Aug 2024

Viewed by 1290

Abstract

Therapeutic vaccination can harness the body’s cellular immune system to target and destroy cancerous cells. Several treatment options are available to eliminate pre-cancerous and cancerous lesions caused by human papillomaviruses (HPV), but may not result in a long-term cure. Therapeutic vaccination may offer an effective, durable, and minimally intrusive alternative. We developed mucosally delivered, recombinant, non-replicating human adenovirus type 5 (rAd5)-vectored vaccines that encode HPV16′s oncogenic proteins E6 and E7 alongside a molecular dsRNA adjuvant. The induction of antigen-specific T cells and the therapeutic efficacy of rAd5 were evaluated in a mouse model of HPV tumorigenesis where E6E7-transformed cells, TC-1, were implanted subcutaneously in C57BL/6 mice. After tumor growth, mice were treated intranasally with rAd5 vaccines expressing the wildtype form of E6E7 (rAd5-16/E6E7_Wt) in combination with an anti-PD-1 antibody or isotype control. Animals treated with rAd5-16/E6E7_Wt with and without anti-PD-1 had significant reductions in tumor volume and increased survival compared to controls. Further, animals treated with rAd5-16/E6E7_Wt had increased CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and produced a cytotoxic tumor microenvironment. In a second study, the immunogenicity of a non-transformative form of E6E7 (rAd5-16/E6E7_Mu) and a vaccine encoding predicted T cell epitopes of E6E7 (rAd5-16/E6E7_epi) were evaluated. These vaccines elicited significant reductions in TC-1 tumor volume and increased survival of animals. Antigen-specific CD8+ T effector memory cells were observed in the animals treated with E6E7-encoding rAd5, but not in the rAd5-empty group. The work described here demonstrates that this mucosal vaccination can be used therapeutically to elicit specific cellular immunity and further identifies a clinical candidate with great potential for the treatment and prevention of human cervical cancer. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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14 pages, 1456 KiB

Open AccessArticle

Longitudinal Screening for Oral High-Risk Non-HPV16 and Non-HPV18 Strains of Human Papillomavirus Reveals Increasing Prevalence among Adult and Pediatric Biorepository Samples: A Pilot Study

by Jordan Jacobs, Eugene Chon and Karl Kingsley

Vaccines 2024, 12(8), 895; https://doi.org/10.3390/vaccines12080895 - 8 Aug 2024

Viewed by 751

Abstract

Most high-risk oral human papillomavirus research has focused on prevalent HPV16 and HPV18, with fewer studies focused on other high-risk strains incorporated into the nine-valent HPV vaccine. Therefore, the objective of this study was to determine the oral prevalence of non-HPV16 and non-HPV18 high-risk strains. A total of n = 251 existing biorepository saliva samples were screened using validated primers and qPCR. A total of n = 72 samples tested positive for HPV, including HPV31, HPV33, HPV35, HPV52, and HPV58. In addition, there were also significant increases in the prevalence of these high-risk strains (2011–2014, 21.3%) following the nine-valent HPV vaccine’s introduction (2015–2019, 36.2%). However, the distribution of HPV-positive samples was nearly equal among males and females (52.8%, 47.2%, respectively, p = 0.5485), although the majority (66.7%) of the HPV-positive samples were within the HPV vaccination age (11 to 26 years) or catch-up range (27 to 45 years). These data demonstrated that the prevalence of high-risk oral HPV may be higher than anticipated, highly concentrated among patients within the recommended vaccination age range, and may be increasing over time—providing new evidence and support for the nine-valent HPV vaccine that covers these additional high-risk HPV strains. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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14 pages, 1410 KiB

Open AccessArticle

Overview of the Implementation of the First Year of Immunization against Human Papillomavirus across Different Administrative Units in Serbia and Montenegro

by Mirjana Štrbac, Milko Joksimović, Vladimir Vuković, Mioljub Ristić, Goranka Lončarević, Milena Kanazir, Nataša Nikolić, Tatjana Pustahija, Smiljana Rajčević, Stefan Ljubičić, Marko Koprivica, Dragan Laušević and Vladimir Petrović

Vaccines 2024, 12(7), 803; https://doi.org/10.3390/vaccines12070803 - 19 Jul 2024

Viewed by 1039

Abstract

Despite the availability of a safe and effective vaccination, uptake of human papillomavirus (HPV) vaccination remains low worldwide. We aimed to analyze the coverage of HPV immunization during the first year of the immunization program and the sociodemographic characteristics across different administrative units in Serbia and Montenegro. Coverage of HPV vaccination in Serbia for females aged 9–14 and 15–19 years was 5.5% and 5.9%, respectively. The coverage rate of immunization against HPV in Montenegro for girls aged 9–14 years was 22.1%. Within Serbia, only one administrative region (Moravica) had HPV immunization coverage in girls 9–19 years old above 10%, 11 districts had coverage from 5 to 10%, while 13 districts had coverage below 5%. As per Montenegro, two administrative units, Cetinje and Berane, reported the highest coverage, with 39% and 36.4% of vaccinated eligible girls, respectively. When we explored the coverage of HPV immunization among girls aged 9–19 years across different regions in Serbia, we observed that the level of coverage did not correlate with the number of pediatricians or with the population density. In Montenegro, we observed a similar situation. On the other hand, we noticed a statistically significant moderate negative correlation (r = −0.446; p = 0.026) between HPV immunization coverage and the percentage of illiterate women in the administrative units. Comparing the coverage between the two countries we found that the higher coverage in Montenegro corresponded with a smaller number of female populations aged 9–14 years, with higher average net monthly income, with smaller population density and smaller number of pediatricians, among divorced persons, and among those without formal education or incompletely primary education. Taking into account the experiences in Montenegro, increasing immunization coverage in Serbia could be achieved through a more vigorous educational campaign targeting schools, the general population, and healthcare workers as well as by additionally incentivizing those engaged in these activities. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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17 pages, 6135 KiB

Open AccessArticle

Effect of an HPV Vaccination Multi-Level, Multi-Component Program on HPV Vaccination Initiation and Completion in a Pediatric Clinic Network

by Lara S. Savas, Ross Shegog, Erica L. Frost, C. Mary Healy, Dale S. Mantey, Sharon P. Coan, L. Aubree Shay, Travis A. Teague, Juan J. Ferreris, Sharice M. Preston and Sally W. Vernon

Vaccines 2024, 12(5), 510; https://doi.org/10.3390/vaccines12050510 - 8 May 2024

Viewed by 1725

Abstract

Despite clear evidence of the public health benefits of the human papillomavirus (HPV) vaccine in preventing HPV-related cancers and genital warts, underutilization of HPV vaccination in the United States persists. Interventions targeting multi-level determinants of vaccination behavior are crucial for improving HPV vaccination rates. The study’s purpose was to implement and evaluate the adapted Adolescent Vaccination Program (AVP), a clinic-based, multi-level, multi-component intervention aimed at increasing HPV vaccine initiation and completion rates in a five-clinic pediatric network in Bexar County, Texas. The adaptation process was guided by established frameworks and involved formative work with clinic stakeholders. The study utilized a quasi-experimental single group pre- and post- study design, with an external comparison data using the National Immunization Survey-Teen (NIS-Teen) datasets for the same time period to examine the AVP’s effect on HPV vaccination initiation and completion. A series of interrupted time series analyses (ITSA) compared the clinic system patient outcomes (HPV vaccination initiation and completion rates) in the post-intervention to the general adolescent population (NIS-Teen). Of the 6438 patients (11–17 years) with clinic visits during the 3-year study period, HPV vaccination initiation rates increased from 64.7% to 80.2% (p < 0.05) and completion rates increased from 43.2% to 60.2% (p < 0.05). The AVP was effective across various demographic and economic subgroups, demonstrating its generalizability. ITSA findings indicated the AVP improved HPV vaccination initiation and completion rates in clinic settings and that AVP strategies facilitated resilience during the pandemic. The minimal adaptation required for implementation in a new clinic system underscores its feasibility and potential for widespread adoption. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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17 pages, 2236 KiB

Open AccessArticle

Human Papillomavirus Vaccination Acceleration and Introduction in Sub-Saharan Africa: A Multi-Country Cohort Analysis

by Gbadebo Collins Adeyanju, Tene-Alima Essoh, Annick Raissa Sidibe, Furaha Kyesi and Muyi Aina

Vaccines 2024, 12(5), 489; https://doi.org/10.3390/vaccines12050489 - 1 May 2024

Viewed by 2551

Abstract

Background: Cervical cancer, caused by human papillomavirus (HPV) infection, is the second-largest cancer killer of women in low- and middle-income countries. The brunt of the global burden is borne predominantly in Sub-Saharan Africa. In 2020 alone, 70,000 of the 100,000 infected women in Africa died from it, thereby making up 21% of global cervical cancer mortality. The introduction of the HPV vaccine into the National Immunization Program was expected to change the trajectory. However, uptake of the vaccination has been poor, especially for the second dose. Only about half of the countries in Africa currently provide the vaccine. Without urgent intervention, the 2030 global cervical cancer elimination targets will be undermined. The study aims to understand the key challenges facing the HPV vaccine and to develop a roadmap to accelerate the uptake. Method: Fourteen countries were purposively included using a cohort design methodology and the investigation spanned March–July 2023. The Africa region was stratified into three focus-group discussion cohorts (Abidjan, Nairobi and Dar es Salaam), comprising pre-selected countries that have already and those about to introduce the HPV vaccine. In each country, the EPI manager, the NITAG chair or representatives and an HPV-focal researcher were selected participants. The methods involved a collaborative and knowledge-sharing format through regional and country-specific discussions, plenary discussions, and workshop-style group missions. Results: The study reached a total of 78 key stakeholders, comprising 30 participants in cohort one, 21 in cohort two and 27 in cohort three. Key outcomes included the prevalence of declining HPV2 vaccination across all countries in the region; country-specific barriers impeding uptake were identified and strategy for accelerating vaccination demand initiated, e.g., utilizing investments from COVID-19 (e.g., electronic registry and multisector coordination); individual countries developing their respective HPV vaccination recovery and acceleration roadmaps; the identification and inclusion of a zero-dose catch-up strategy into the vaccination roadmaps; support for a transition from multiple-doses to a single-dose HPV vaccine; the incorporation of implementation science research to support the decision-making process such as vaccine choices, doses and understanding behavior. Conclusion: Beyond research, the study shows the significance of scientific approaches that are not limited to understanding problems, but are also solution-oriented, e.g., development of roadmaps to overcome barriers against HPV vaccination uptake. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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16 pages, 8455 KiB

Open AccessArticle

Immunoinformatics Design and In Vivo Immunogenicity Evaluation of a Conserved CTL Multi-Epitope Vaccine Targeting HPV16 E5, E6, and E7 Proteins

by Ni Guo, Zhixin Niu, Zhiling Yan, Weipeng Liu, Lei Shi, Chuanyin Li, Yufeng Yao and Li Shi

Vaccines 2024, 12(4), 392; https://doi.org/10.3390/vaccines12040392 - 9 Apr 2024

Viewed by 1783

Abstract

Human papillomavirus type 16 (HPV16) infection is responsible for more than 50% of global cervical cancer cases. The development of a vaccine based on cytotoxic T-lymphocyte (CTL) epitopes is a promising strategy for eliminating pre-existing HPV infections and treating patients with cervical cancer. In this study, an immunoinformatics approach was used to predict HLA-I-restricted CTL epitopes in HPV16 E5, E6, and E7 proteins, and a set of conserved CTL epitopes co-restricted by human/murine MHCs was screened and characterized, with the set containing three E5, four E6, and four E7 epitopes. Subsequently, the immunogenicity of the epitope combination was assessed in mice, and the anti-tumor effects of the multi-epitope peptide vaccine E5E6E7pep11 and the recombinant protein vaccine CTB-Epi11E567 were evaluated in the TC-1 mouse tumor model. The results demonstrated that mixed epitope peptides could induce antigen-specific IFN-γ secretion in mice. Prophylactic immunization with E5E6E7pep11 and CTB-Epi11E567 was found to provide 100% protection against tumor growth in mice. Moreover, both types of the multi-epitope vaccine significantly inhibited tumor growth and prolonged mouse survival. In conclusion, in this study, a multi-epitope vaccine targeting HPV16 E5, E6, and E7 proteins was successfully designed and evaluated, demonstrating potential immunogenicity and anti-tumor effects and providing a promising strategy for immunotherapy against HPV-associated tumors. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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15 pages, 241 KiB

Open AccessArticle

“You Don’t Know If It’s the Truth or a Lie”: Exploring Human Papillomavirus (HPV) Vaccine Hesitancy among Communities with Low HPV Vaccine Uptake in Northern California

by Julie H. T. Dang, Alexandra Gori, Lucy Rios, Angelica M. Rolon, Jingwen Zhang and Moon S. Chen, Jr.

Vaccines 2024, 12(4), 372; https://doi.org/10.3390/vaccines12040372 - 1 Apr 2024

Viewed by 2130

Abstract

Background: Vaccine hesitancy, delaying or refusing to vaccinate despite the availability of vaccines, impedes the progress of achieving optimal HPV vaccine coverage. Little is known about the sources of human papillomavirus (HPV) vaccine hesitancy among racially/ethnically and geographically diverse communities. The purpose of this paper is to explore HPV vaccine hesitancy among rural, Slavic, and Latino communities that reside in counties with low HPV vaccine uptake rates. Methods: Key informant interviews and focus groups were conducted with rural, Slavic, and Latino communities that reside within counties in California that have low HPV vaccine up to date rates (16–25%). Qualitative data were transcribed verbatim and analyzed using inductive and deductive thematic analysis. Results: A total of seven focus groups and 14 key informant interviews were conducted with 39 individuals from seven California counties. Salient themes that contributed to HPV vaccine hesitancy included the following: social media and the anti-vaccination movement; a strong belief in acquiring immunity naturally; prior vaccine experiences; and vaccine timing concerns. Participants suggested the provision of culturally appropriate, in-language, in-person easy to understand HPV vaccine education to mitigate HPV vaccine hesitancy. Conclusions: Our findings can inform future interventions to increase HPV vaccine uptake among hesitant communities. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

10 pages, 256 KiB

Open AccessArticle

Knowledge of HPV and HPV Vaccination among Polish Students from Medical and Non-Medical Universities

by Dominik Pruski, Sonja Millert-Kalińska, Jan Haraj, Sandra Dachowska, Robert Jach, Jakub Żurawski and Marcin Przybylski

Vaccines 2023, 11(12), 1850; https://doi.org/10.3390/vaccines11121850 - 14 Dec 2023

Cited by 2 | Viewed by 1960

Abstract

Human papillomavirus (HPV) is a common sexually transmitted infection that can cause both benign and malignant lesions. HPV vaccines, preferably administered before the onset of sexual activity, have demonstrated remarkable efficacy in preventing HPV-related cancers. The impact of a healthcare provider’s recommendation on HPV vaccine acceptance is substantial. Therefore, medical students must undergo thorough training in this domain. This study compares fundamental understanding and viewpoints regarding HPV and anti-HPV vaccines among Polish students pursuing medical and non-medical sciences. This study was based on the authors’ questionnaire, and the results were statistically analyzed. The participants in this study were 1025 students (medical sciences students—520 respondents in total; and non-medical sciences students—505 respondents in total). According to the results, medical students’ knowledge about the consequences of HPV infection and vaccination against HPV was significantly greater. To date, numerous publications have investigated the understanding of particular social, gender, parental, etc., groups about vaccination, but the knowledge of students at different universities—medical and other—has not been compared. Social awareness is still insufficient, even in groups of medical students. There is much to be done to educate and encourage preventive behavior in those not receiving primary prevention in early childhood. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

14 pages, 266 KiB

Open AccessArticle

Knowledge and Attitudes towards Human Papillomavirus Vaccination (HPV) among Healthcare Providers Involved in the Governmental Free HPV Vaccination Program in Shenzhen, Southern China

by Danhong Song, Peiyi Liu, Dadong Wu, Fanghui Zhao, Yueyun Wang and Yong Zhang

Vaccines 2023, 11(5), 997; https://doi.org/10.3390/vaccines11050997 - 18 May 2023

Cited by 6 | Viewed by 2323

Abstract

No research has been conducted to explore the variables associated with healthcare providers’ (HCPs) knowledge and attitudes toward the human papillomavirus vaccine (HPV) since the vaccine was approved for free use in some Chinese cities. In Shenzhen, southern China, a convenience sample strategy was used to distribute questionnaires to HCPs involved in the government’s HPV vaccination program from Shenzhen. There were 828 questionnaires collected in total, with 770 used in the analysis. The mean HPV and HPV vaccine knowledge score was 12.0 among HCPs involved in the government HPV vaccination program (with a total score of 15). the average scores for HPV and HPV vaccine knowledge varied among different types of medical institutions. District hospitals had the highest mean score of 12.4, while private hospitals ranked fourth with a mean score of 10.9. Multivariate logistic regression results revealed significant disparities in the type of license and after-tax annual income across HCPs (p < 0.05). The future education and training for HCPs should focus on private community health centers (CHCs), HCPs whose license type is other than a doctor, and HCPs with low after-tax annual income. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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17 pages, 1210 KiB

Open AccessSystematic Review

School Teachers’ Perceptions of Adolescent Human Papillomavirus (HPV) Vaccination: A Systematic Review

by Jihye Choi, Efrat K. Gabay and Paula M. Cuccaro

Vaccines 2024, 12(4), 361; https://doi.org/10.3390/vaccines12040361 - 27 Mar 2024

Viewed by 1963

Abstract

School nurses are uniquely positioned to educate students about immunizations, including human papillomavirus (HPV) vaccination, but schools are often without a nurse for different reasons. In lieu of nurses, teachers who closely interact with students and are traditionally well-trusted by parents may be able to communicate about HPV vaccination, alleviating parental vaccine hesitancy. This systematic review explores school teachers’ perspectives on adolescent HPV vaccination and factors influencing their willingness to make vaccine recommendations. We searched three databases with appropriate medical subject headings and keywords to identify relevant studies. We reviewed fifteen studies and provided an extensive summary and a comparison of the results across the studies. Teachers had low to moderate levels of HPV knowledge with low self-efficacy to counsel parents about the HPV vaccine and expressed concerns about the vaccine condoning adolescent sexual activity, vaccine side effects, and parental disapproval. Nonetheless, some teachers showed interest in learning about vaccine effectiveness in preventing HPV-associated cancers and wanted guidance on vaccine communication with parents, viewing schools as adequate venues to promote and deliver HPV vaccines. Schools should consider educating teachers on HPV and HPV vaccination, with a focus on effective vaccine communication practices to increase adolescent HPV vaccine uptake. Full article

(This article belongs to the Special Issue Recent Research on Human Papillomavirus (HPV) Infection and Vaccination)

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