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Pathogens
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Latest Advances in Human Papillomavirus (HPV) Research
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Latest Advances in Human Papillomavirus (HPV) Research

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 21845

Special Issue Editors

Dr. Paul Licciardi

E-Mail Website
Guest Editor
Infection and Immunity, Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
Interests: human papillomavirus vaccines; immunogenicity; correlates of protection
Special Issues, Collections and Topics in MDPI journals
Dr. Zheng Quan Toh

E-Mail Website
Guest Editor
Infection and Immunity, Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
Interests: infection; immunity; global health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human papillomavirus (HPV) causes a range of diseases from benign anogenital warts to anogenital cancers, particularly cervical cancer. HPV was first discovered to cause cervical cancer in the 1980s, and since then, there have been several major scientific breakthroughs that have led to the development and implementation of highly effective prophylactic HPV vaccines, cervical cancer screening programs, and treatment of cervical lesions. These important discoveries build upon key basic science research and technological advancement that has enabled novel discoveries within HPV research. In 2018, the Director-General of the World Health Organization made a pledge to eliminate cervical cancer as a public health problem within the next century and outlined a strategy encompassing HPV vaccination, screening, and treatment. However, significant barriers remain to cervical cancer elimination globally, and research into novel HPV diagnostics and therapeutics as well as intervention research will be important to overcome these barriers. This Special Issue aims to present the latest research into HPV in the hope that it will contribute new knowledge to the field as well as ultimately aid in achieving the cervical cancer elimination goal.

Dr. Paul Licciardi
Dr. Zheng Quan Toh
Guest Editors

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Keywords

  • human papillomavirus
  • vaccine
  • immune response
  • pathogenesis
  • cervical cancer screening
  • treatment

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Published Papers (7 papers)

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Research

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13 pages, 634 KiB  
Article
Human Papillomavirus (HPV) Infection and Risk Behavior in Vaccinated and Non-Vaccinated Paraguayan Young Women
by María Liz Bobadilla, Verónica Villagra, Héctor Castro, Marta von Horoch, Soraya Araya, Gerardo Deluca and Vanessa Salete de Paula
Pathogens 2024, 13(3), 209; https://doi.org/10.3390/pathogens13030209 - 27 Feb 2024
Viewed by 2442
Abstract
Cervical cancer is a global health concern and ranks fourth among the most prevalent cancers in women worldwide. Human papillomavirus (HPV) infection is a known precursor of cervical cancer and preventive measures include prophylactic vaccines. This study focused on sexually active Paraguayan women [...] Read more.
Cervical cancer is a global health concern and ranks fourth among the most prevalent cancers in women worldwide. Human papillomavirus (HPV) infection is a known precursor of cervical cancer and preventive measures include prophylactic vaccines. This study focused on sexually active Paraguayan women aged 18–25 years, exploring the intersection of HPV vaccination and sexual behavior. Among 254 participants, 40.9% received the Gardasil-4 vaccine, with no significant differences in sexual behavior between the vaccinated and unvaccinated sexually active groups. However, a notable decrease in the prevalence of HPV among the vaccinated women highlights the efficacy of this vaccine in reducing infections. The prevalence of any HPV type was 37.5% in vaccinated participants compared to 56.7% in unvaccinated participants (p = 0.0026). High-risk HPV types showed a significant difference, with a prevalence of 26.0% in vaccinated women compared with 52.7% in unvaccinated women (p < 0.001). Although a potential decline in genital warts was observed among the vaccinated individuals, statistical significance (p = 0.0564) was not reached. Despite the challenges in achieving high vaccination coverage, the observed reduction in HPV prevalence underscores the importance of ongoing monitoring, healthcare professional recommendations, and comprehensive risk management. These findings contribute to dispelling concerns about HPV vaccination influencing sexual behavior, advocating further large-scale research to explore the impact of vaccines on various HPV types and potential cross-protection. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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16 pages, 2575 KiB  
Article
HPV and Other Risk Factors Involved in Pharyngeal Neoplasm—Clinical and Morphopathological Correlations in the Southwestern Region of Romania
by Carmen Aurelia Mogoantă, Mircea Sorin Ciolofan, Anca-Maria Istrate-Ofițeru, Stelian-Ștefăniță Mogoantă, Gabriela-Camelia Roșu, Florin Anghelina, Alina-Nicoleta Căpitanescu, Ioana Cristina Opriscan, Nina Ionovici, Mihaela Roxana Mitroi, Oana Badea and Gheorghe Iovănescu
Pathogens 2023, 12(8), 984; https://doi.org/10.3390/pathogens12080984 - 27 Jul 2023
Cited by 2 | Viewed by 1165
Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) development is strongly associated with risk factors like smoking, chronic alcohol consumption, and the living environment, but also chronic human papilloma virus (HPV) infection, which can trigger cascade cellular changes leading to a neoplastic transformation. The prevalence of [...] Read more.
Oropharyngeal squamous cell carcinoma (OPSCC) development is strongly associated with risk factors like smoking, chronic alcohol consumption, and the living environment, but also chronic human papilloma virus (HPV) infection, which can trigger cascade cellular changes leading to a neoplastic transformation. The prevalence of these factors differs among different world regions, and the prevention, diagnosis, and prognosis of OPSCC are highly dependent on them. We performed a retrospective study on 406 patients diagnosed with OPSCC in our region that were classified according to the tumor type, localization and diagnosis stage, demographic characteristics, risk factors, and histological and immunohistochemical features. We found that most of the patients were men from urban areas with a smoking habit, while most of the women in our study were diagnosed with tonsillar OPSCC and had a history of chronic alcoholism. During the immunohistochemical study, we analyzed the tumor immunoreactivity against anti-p16 and anti-HPV antibodies as markers of HPV involvement in tumor progression, as well as the correlation with the percentage of intratumoral nuclei immunomarked with the anti-Ki 67 antibody in serial samples. We observed that the percentage of Ki67-positive nuclei increased proportionally with the presence of intratumoral HPV; thus, active HPV infection leads to an increase in the rate of tumor progression. Our results support the implementation of strategies for OPSCC prevention and early diagnosis and can be a starting point for future studies aiming at adapting surgical and oncological treatment according to the HPV stage for better therapeutic results. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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13 pages, 856 KiB  
Article
Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer
by Yasmin L. Jayasinghe, Sepehr N. Tabrizi, Matthew Stevens, Trishe Y-M. Leong, Jan Pyman, Sonia R. Grover, Suzanne M. Garland and the Early-Onset Cervical Cancer (EOCC) Study Group
Pathogens 2023, 12(3), 451; https://doi.org/10.3390/pathogens12030451 - 13 Mar 2023
Cited by 1 | Viewed by 2186
Abstract
Background: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the [...] Read more.
Background: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. Methods: HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. Results: HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7–97.7). Conclusions: Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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10 pages, 843 KiB  
Article
Association and Effectiveness of PAX1 Methylation and HPV Viral Load for the Detection of Cervical High-Grade Squamous Intraepithelial Lesion
by Mingzhu Li, Chao Zhao, Yun Zhao, Jingran Li, Xiaobo Zhang, Wei Zhang, Qingqing Gao and Lihui Wei
Pathogens 2023, 12(1), 63; https://doi.org/10.3390/pathogens12010063 - 30 Dec 2022
Cited by 4 | Viewed by 3129
Abstract
Background: PAX1 methylation (PAX1m) and HPV viral load (VL) have been reported to detect cervical high-grade squamous intraepithelial lesions (HSIL), but the relationship between them is unclear. This study aimed to evaluate the correlation between HPV VL and PAX1m and [...] Read more.
Background: PAX1 methylation (PAX1m) and HPV viral load (VL) have been reported to detect cervical high-grade squamous intraepithelial lesions (HSIL), but the relationship between them is unclear. This study aimed to evaluate the correlation between HPV VL and PAX1m and its effectiveness in predicting cervical lesions. (2) Methods: A total of 476 women referred to colposcopy for abnormal cervical screening at the Peking University People’s Hospital between November 2020 and November 2021 were enrolled. PAX1m and HPV VL were determined by QMSP and BMRT-HPV reports type-specific VL/10,000 cells, respectively. (3) Results: PAX1m was significantly increased in HSIL, especially in cervical cancer, but there was no significant difference between cervical intraepithelial neoplasms 1(CIN1) and CIN2. However, HPV VL significantly differed between CIN1 and CIN2 but not between CIN3 and cervical cancer. In general, PAX1m positively correlated with all hrHPV VL, mainly in the HPV16/18 VL (p < 0.001), but had no relationship with the other 12 types of hrHPV VL. PAX1m had the highest specificity in diagnosing CIN2+, followed by HPV16/18 VL, which are higher than cytology ≥ASCUS. (4) Conclusions: Hypermethylation of PAX1 is associated with high HPV VL, especially HPV16/18, and both present advantageous specificity in detecting CIN2+. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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13 pages, 2640 KiB  
Article
Expression of HIF-1α and Genes Involved in Glucose Metabolism Is Increased in Cervical Cancer and HPV-16-Positive Cell Lines
by Víctor D. Priego-Hernández, Adán Arizmendi-Izazaga, Diana G. Soto-Flores, Norma Santiago-Ramón, Milagros D. Feria-Valadez, Napoleón Navarro-Tito, Hilda Jiménez-Wences, Dinorah N. Martínez-Carrillo, Eric G. Salmerón-Bárcenas, Marco A. Leyva-Vázquez, Berenice Illades-Aguiar, Luz del C. Alarcón-Romero and Julio Ortiz-Ortiz
Pathogens 2023, 12(1), 33; https://doi.org/10.3390/pathogens12010033 - 25 Dec 2022
Cited by 10 | Viewed by 3088
Abstract
Cervical cancer (CC) is the most common cancer in women in the lower genital tract. The main risk factor for developing CC is persistent infection with HPV 16. The E6 and E7 oncoproteins of HPV 16 have been related to metabolic reprogramming in [...] Read more.
Cervical cancer (CC) is the most common cancer in women in the lower genital tract. The main risk factor for developing CC is persistent infection with HPV 16. The E6 and E7 oncoproteins of HPV 16 have been related to metabolic reprogramming in cancer through the regulation of the expression and stability of HIF-1α and consequently of the expression of its target genes, such as HIF1A (HIF-1α), SLC2A1 (GLUT1), LDHA, CA9 (CAIX), SLC16A3 (MCT4), and BSG (Basigin or CD147), which are involved in glucose metabolism. This work aimed to evaluate the expression of HIF-1α, GLUT1, LDHA, CAIX, MCT4, and Basigin in patient samples and CC cell lines. To evaluate the expression level of HIF1A, SLC2A1, LDHA, CA9, SLC16A3, and BSG genes in tissue from patients with CC and normal tissue, the TCGA dataset was used. To evaluate the expression level of these genes by RT-qPCR in CC cell lines, HPV-negative (C-33A) and HPV-16-positive (SiHa and Ca Ski) cell lines were used. Increased expression of HIF1A, SLC2A1, LDHA, SLC16A3, and BSG was found in Ca Ski and CA9 in SiHa compared to C-33A. Similar results were observed in CC tissues compared to normal tissue obtained by bioinformatics analysis. In conclusion, the expression of HIF-1α, GLUT1, LDHA, CAIX, MCT4, and BSG genes is increased in CC and HPV-16-positive cell lines. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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Review

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30 pages, 1333 KiB  
Review
Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems
by Ingrid Andrêssa de Moura, Anna Jéssica Duarte Silva, Larissa Silva de Macêdo, Maria da Conceição Viana Invenção, Mylenna Máyra Gois de Sousa and Antonio Carlos de Freitas
Pathogens 2022, 11(12), 1444; https://doi.org/10.3390/pathogens11121444 - 30 Nov 2022
Cited by 9 | Viewed by 3567
Abstract
Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on [...] Read more.
Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used—due to its impact on the immune response and desired final effect. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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Other

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14 pages, 626 KiB  
Systematic Review
Do We Have Enough Evidence to Specifically Recommend Transoral Robotic Surgery in HPV−Driven Oropharyngeal Cancer? A Systematic Review
by Armando De Virgilio, Andrea Costantino, Davide Rizzo, Claudia Crescio, Roberto Gallus, Giuseppe Spriano, Giuseppe Mercante, Bianca Maria Festa, Remo Accorona, Lorenzo Pignataro, Pasquale Capaccio and Francesco Bussu
Pathogens 2023, 12(2), 160; https://doi.org/10.3390/pathogens12020160 - 18 Jan 2023
Cited by 4 | Viewed by 2336
Abstract
Introduction: International guidelines include transoral robotic surgery (TORS) as an option for selected oropharyngeal squamous cell carcinomas (OPSCCs). In the perspective of treatment de-intensification, many surgeons have started recommending and performing TORS preferentially in p16- positive OPSCC in order to reduce the [...] Read more.
Introduction: International guidelines include transoral robotic surgery (TORS) as an option for selected oropharyngeal squamous cell carcinomas (OPSCCs). In the perspective of treatment de-intensification, many surgeons have started recommending and performing TORS preferentially in p16- positive OPSCC in order to reduce the long-term morbidity related to chemoradiotherapy. The aim of the present review is to analyze the current evidence supporting the above-cited strategy. Materials and Methods: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Twenty-two studies were included in this review, with a total of 3992 patients treated with primary TORS. The majority of patients were classified as HPV+ (n = 3655, 91.6%), and 8.2% (n = 327) as HPV−. The HPV status was unknown in only 10 (0.3%) patients. In particular, only five of the included studies compared survival outcomes of HPV−positive patients with HPV−negative ones treated with primary TORS, and only two of these found a significant improvement in survival in the HPV−driven cohort. Discussion: The current literature does not clarify whether HPV+ OPSCCs treated with TORS, alone or with adjuvant treatments, are associated with a better oncologic and/or functional outcome compared to those treated with radio- or chemoradiotherapy. However, TORS alone obtained good oncological outcomes in a high percentage of cases in the reviewed series. Recent data, on the other hand, suggest that TORS could represent a promising strategy for intensifying treatments in HPV− OPSCC. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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