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Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment
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Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment

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

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 10153

Special Issue Editor

Prof. Dr. Kouya Shiraishi

E-Mail Website
Guest Editor
Division of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: cancer genome; germline variations; cancer prevention

Special Issue Information

Dear Colleagues,

Cervical cancer is the fourth most common cancer among women worldwide, and the fourth most common cause of cancer-related deaths. It is primarily caused by persistent infection by carcinogenic strains of human papillomavirus (HPV), especially strains 16 and 18. The HPV vaccine has reduced the incidence of cervical cancer by 87％ in women aged 20–30 years who were offered the vaccine when they were aged 12–13 years as part of the UK HPV vaccination program. Although safe and effective prophylactic vaccines against the most carcinogenic forms of HPV are widely available, the HPV vaccination rate in low- and middle-income countries is low compared with that of other routine childhood immunizations. Furthermore, cervical cancer screening rates among women are relatively low, and the incidence of invasive cervical cancer has not decreased. HPV vaccine recommendations were resumed in 2022, but it will take more than 10 years for the vaccination efforts to translate into a tangible and effective reduction in cervical cancer incidence rates, since the target age group for vaccination is 12–16 years old. Therefore, continued research into prevention, screening, and novel treatments for HPV-associated cervical cancer is required during this lag period, especially in countries where vaccination is still not widely available. In this Special Issue, the latest developments in this field will be presented.

Prof. Dr. Kouya Shiraishi 
Guest Editor

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Keywords

  • cervical cancer
  • HPV vaccination
  • prevention
  • screening
  • treatment
  • genome alternations

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Published Papers (5 papers)

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Research

17 pages, 3029 KiB  
Article
Cultivable Microbiome Approach Applied to Cervical Cancer Exploration
by Irma Berenice Mulato-Briones, Ismael Olan Rodriguez-Ildefonso, Julián Antonio Jiménez-Tenorio, Patricia Isidra Cauich-Sánchez, María del Socorro Méndez-Tovar, Gerardo Aparicio-Ozores, María Yicel Bautista-Hernández, Juan Francisco González-Parra, Jesús Cruz-Hernández, Ricardo López-Romero, Teresita María del Rosario Rojas-Sánchez, Raúl García-Palacios, Ónix Garay-Villar, Teresa Apresa-García, Juan López-Esparza, Daniel Marrero, Juan Arturo Castelán-Vega, Alicia Jiménez-Alberto, Mauricio Salcedo and Rosa María Ribas-Aparicio
Cancers 2024, 16(2), 314; https://doi.org/10.3390/cancers16020314 - 11 Jan 2024
Cited by 2 | Viewed by 1706
Abstract
Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under [...] Read more.
Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role. Full article
(This article belongs to the Special Issue Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment)
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20 pages, 2282 KiB  
Article
Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors’ PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen
by Joana Daradoumis, Mikkel Dons Müller, Patrick Neckermann, Benedikt Asbach, Silke Schrödel, Christian Thirion, Ralf Wagner, Per thor Straten, Peter Johannes Holst and Ditte Boilesen
Cancers 2023, 15(24), 5863; https://doi.org/10.3390/cancers15245863 - 15 Dec 2023
Cited by 1 | Viewed by 1629
Abstract
Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from [...] Read more.
Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples. Full article
(This article belongs to the Special Issue Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment)
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15 pages, 956 KiB  
Article
Triage Strategies for Non-16/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16/Ki67 Dual Stain vs. Cytology
by Karolina Mazurec, Martyna Trzeszcz, Maciej Mazurec, Joanna Streb, Agnieszka Halon and Robert Jach
Cancers 2023, 15(20), 5095; https://doi.org/10.3390/cancers15205095 - 21 Oct 2023
Cited by 4 | Viewed by 2047
Abstract
Background: In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. [...] Read more.
Background: In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. However, there remains a dearth of comprehensive data for comparing their performance. Methods: Among 30,066 results from liquid-based cervical cancer screening tests, a cohort of 332 cases was meticulously selected based on available high-risk human papillomavirus (HPV) test results, limited genotyping for HPV 16 and 18, liquid-based cytology, DS, and histology outcomes from standardized colposcopy with biopsy. For cases positive for 12 other high-risk HPV genotypes, three retrospective triage approaches were analyzed. We computed the positive predictive value (PPV) for the detection of high-grade squamous intraepithelial lesions or worse (HSIL+). Results: Both triage models employing DS (reflex cytology followed by DS and reflex DS alone in all cases) exhibited significantly higher PPV for HSIL+ compared to the strategy with reflex cytology alone (35.9%/33.3% vs. 18.8%; p < 0.0001). Additionally, these DS-based models showed higher negative predictive values (NPV) (100%/96.2% vs. 69.2%; p = 0.0024/0.0079). In the DS-inclusive models, fewer colposcopies were necessitated (103/102 vs. 154), and fewer cases of HSIL+ were overlooked (0/3 vs. 8). Conclusions: Our findings suggest that p16/Ki67 dual-stain, either as a standalone or combined triage test, holds promise for the effective detection of HSIL+ in patients with minor screening abnormalities in primary HPV-based cervical cancer screening. Full article
(This article belongs to the Special Issue Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment)
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23 pages, 2883 KiB  
Article
Interaction between Human Papillomavirus-Encoded E6 Protein and AurB Induces Cell Immortalization and Proliferation—A Potential Target of Intervention
by Siaw Shi Boon, Yin Ching Lee, Ka Lai Yip, Ho Yin Luk, Chuanyun Xiao, Man Kin Yim, Zigui Chen and Paul Kay Sheung Chan
Cancers 2023, 15(9), 2465; https://doi.org/10.3390/cancers15092465 - 25 Apr 2023
Cited by 2 | Viewed by 1672
Abstract
The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we identified, for the first time, that Aurora kinase B (AurB) is a bona [...] Read more.
The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we identified, for the first time, that Aurora kinase B (AurB) is a bona fide interacting partner of E6. We systematically characterized the AurB-E6 complex formation and its consequences in carcinogenesis using a series of in vitro and cell-based assays. We also assessed the efficacy of Aurora kinase inhibitors in halting HPV-mediated carcinogenesis using in vitro and in vivo models. We showed that AurB activity was elevated in HPV-positive cells, and this correlated positively with the E6 protein level. E6 interacted directly with AurB in the nucleus or mitotic cells. A previously unidentified region of E6, located upstream of C-terminal E6-PBM, was important for AurB-E6 complex formation. AurB-E6 complex led to reduced AurB kinase activity. However, the AurB-E6 complex increased the hTERT protein level and its telomerase activity. On the other hand, AurB inhibition led to the inhibition of telomerase activity, cell proliferation, and tumor formation, even though this may occur in an HPV-independent manner. In summary, this study dissected the molecular mechanism of how E6 recruits AurB to induce cell immortalization and proliferation, leading to the eventual cancer development. Our findings revealed that the treatment of AZD1152 exerted a non-specific anti-tumor effect. Hence, a continuous effort to seek a specific and selective inhibitor that can halt HPV-mediated carcinogenesis should be warranted. Full article
(This article belongs to the Special Issue Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment)
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13 pages, 1288 KiB  
Article
Impact of Preventive Strategies on HPV-Related Diseases: Ten-Year Data from the Italian Hospital Admission Registry
by Vincenzo Restivo, Giuseppa Minutolo, Marianna Maranto, Antonio Maiorana, Francesco Vitale, Alessandra Casuccio and Emanuele Amodio
Cancers 2023, 15(5), 1452; https://doi.org/10.3390/cancers15051452 - 24 Feb 2023
Cited by 6 | Viewed by 1919
Abstract
Human papillomavirus (HPV)-related diseases are still a challenge for public health. Some studies have shown the effects of preventive strategies on them, but studies at the national level are few in number. Therefore, a descriptive study through hospital discharge records (HDRs) was conducted [...] Read more.
Human papillomavirus (HPV)-related diseases are still a challenge for public health. Some studies have shown the effects of preventive strategies on them, but studies at the national level are few in number. Therefore, a descriptive study through hospital discharge records (HDRs) was conducted in Italy between 2008 and 2018. Overall, 670,367 hospitalizations due to HPV-related diseases occurred among Italian subjects. In addition, a significant decrease in hospitalization rates for cervical cancer (average annual percentage change (AAPC) = −3.8%, 95% CI = −4.2, −3.5); vulval and vaginal cancer (AAPC = −1.4%, 95% CI = −2.2, −0.6); oropharyngeal cancer; and genital warts (AAPC = −4.0%, 95% CI = −4.5, −3.5) was observed during the study period. Furthermore, strong inverse correlations were found between screening adherence and invasive cervical cancer (r = −0.9, p < 0.001), as well as between HPV vaccination coverage and in situ cervical cancer (r = −0.8, p = 0.005). These results indicate the positive impact of HPV vaccination coverage and cervical cancer screening on hospitalizations due to cervical cancer. Indeed, HPV vaccination also resulted in a positive impact on the decrease in hospitalization rates due to other HPV-related diseases. Full article
(This article belongs to the Special Issue Human Papilloma Virus (HPV)—Cervical Cancer Prevention, Screening, and Treatment)
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