Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 10737

Special Issue Editors


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Guest Editor
1. División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara C.P. 44340, Jalisco, Mexico
2. Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara C.P. 44340, Jalisco, Mexico
Interests: HPV genotyping; HPV oncogenes function; biomarkers of cervical cancer

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Guest Editor
1. División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara C.P. 44340, Jalisco, Mexico
2. Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara C.P. 44340, Jalisco, Mexico
Interests: molecular oncology; cervical cancer; HPV-mediated oncogenesis; immune evasion

Special Issue Information

Dear Colleagues,

Persistent human papillomavirus (HPV) infection is the principal etiological factor of the development of cervical cancer and various other types of neoplasms. According to their oncogenic potential, HPVs have been classified as low risk (LR-HPV) and high risk (HR-HPV); however, thanks to next-generation sequencing, more and more complete sequences of HPVs have been reported, and many of them have already been classified as new genotypes, but a large number still remains unclassified.On the other hand, since the first publications of the oncogenicity of HPV 16 and 18, molecular biology techniques have rapidly evolved, which has allowed deepening or discovering new strategies that these viruses use to alter the cellular environment and evade the immune response. This Special Issue aims to deepen our understanding of the molecular and immunological mechanisms that human papillomaviruses have developed to establish viral infection, cell transformation, and cancer development, so original research related to the processes mentioned above are welcome, as well as studies that include HPV genotyping with next-generation sequencing (NGS). In addition, reviews on a specific topic are also welcome.

Dr. Adriana Aguilar-Lemarroy
Dr. Luis Felipe Jave-Suárez
Guest Editors

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Keywords

  • HPV infection
  • transformation
  • carcinogenesis
  • immune evasion
  • oncogenes
  • biomarkers
  • HPV genotyping by NGS

Published Papers (5 papers)

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Research

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16 pages, 915 KiB  
Article
Haplotype Structures and Protein Levels of TGFB1 in HPV Infection and Cervical Lesion: A Case-Control Study
by Kleber Paiva Trugilo, Guilherme Cesar Martelossi Cebinelli, Érica Romão Pereira, Nádia Calvo Martins Okuyama, Fernando Cezar-dos-Santos, Eliza Pizarro Castilha, Tamires Flauzino, Valéria Bumiller-Bini Hoch, Maria Angelica Ehara Watanabe, Roberta Losi Guembarovski and Karen Brajão de Oliveira
Cells 2023, 12(1), 84; https://doi.org/10.3390/cells12010084 - 25 Dec 2022
Cited by 1 | Viewed by 1425
Abstract
This study aimed to verify the role of TGFB1 variants (c.–1638G>A, c.–1347C>T, c.29C>T, and c.74G>C) in HPV infection susceptibility and cervical lesions development, and their impact on TGFB1 cervical and plasma levels. TGFB1 genotypes were assessed with PCR-RFLP and haplotypes were inferred for [...] Read more.
This study aimed to verify the role of TGFB1 variants (c.–1638G>A, c.–1347C>T, c.29C>T, and c.74G>C) in HPV infection susceptibility and cervical lesions development, and their impact on TGFB1 cervical and plasma levels. TGFB1 genotypes were assessed with PCR-RFLP and haplotypes were inferred for 190 HPV-uninfected and 161 HPV-infected women. TGFB1 levels were determined with immunofluorimetric assay. Case-control analyses were performed with logistic regression adjusted for possible confounders. Women carrying –1347TT or –1347CT+TT as well as those with 29CT, 29CC, or 29CT+CC were more likely to have HPV than –1347CC and 29TT carriers, respectively. Regarding haplotypes, the most frequent were *4 (GCTG) and *3 (GTCG). Women *4/*4 were less likely to have HPV than those with no *4 copy. Comparing the inheritance of *3 and *4, carriers of *3/*4 or *3/*3 were more susceptible to HPV than *4/*4. The TGFB1 plasma and cervical levels were higher in the infected patients. Plasma levels were also higher in infected women with low-grade lesions. HPV-infected patients carrying *3/Other and *3/Other+*3/*3 presented lower TGFB1 plasma levels than those with no copy of *3. TGFB1 variants could contribute to the comprehension of the TGFB1 role in HPV-caused cervical disease. Full article
(This article belongs to the Special Issue Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis)
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21 pages, 4836 KiB  
Article
RIPOR2 Expression Decreased by HPV-16 E6 and E7 Oncoproteins: An Opportunity in the Search for Prognostic Biomarkers in Cervical Cancer
by Leslie Olmedo-Nieva, J. Omar Muñoz-Bello, Imelda Martínez-Ramírez, Antonio Daniel Martínez-Gutiérrez, Yunuen Ortiz-Pedraza, Claudia González-Espinosa, Vicente Madrid-Marina, Kirvis Torres-Poveda, Margarita Bahena-Roman and Marcela Lizano
Cells 2022, 11(23), 3942; https://doi.org/10.3390/cells11233942 - 06 Dec 2022
Cited by 4 | Viewed by 1847
Abstract
High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival [...] Read more.
High-risk human papillomavirus (HPV) infection is the main risk factor for cervical cancer (CC) development, where the continuous expression of E6 and E7 oncoproteins maintain the malignant phenotype. In Mexico, around 70% of CC cases are diagnosed in advanced stages, impacting the survival of patients. The aim of this work was to identify biomarkers affected by HPV-16 E6 and E7 oncoproteins that impact the prognosis of CC patients. Expression profiles dependent on E6 and E7 oncoproteins, as well as their relationship with biological processes and cellular signaling pathways, were analyzed in CC cells. A comparison among expression profiles of E6- and E7-expressing cells and that from a CC cohort obtained from The Cancer Genome Atlas (TCGA) demonstrated that the expression of 13 genes impacts the overall survival (OS). A multivariate analysis revealed that the downregulated expression of RIPOR2 was strongly associated with a worse OS. RIPOR2, including its transcriptional variants, were overwhelmingly depleted in E6- and E7-expressing cells. Finally, in a Mexican cohort, it was found that in premalignant cervical lesions, RIPOR2 expression decreases as the lesions progress; meanwhile, decreased RIPOR2 expression was also associated with a worse OS in CC patients. Full article
(This article belongs to the Special Issue Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis)
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21 pages, 2978 KiB  
Article
Reduced MHC Class I and II Expression in HPV−Negative vs. HPV−Positive Cervical Cancers
by Andris M. Evans, Mikhail Salnikov, Tanner M. Tessier and Joe S. Mymryk
Cells 2022, 11(23), 3911; https://doi.org/10.3390/cells11233911 - 03 Dec 2022
Cited by 6 | Viewed by 2006
Abstract
Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV−negative (HPV−) CC represents [...] Read more.
Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV−negative (HPV−) CC represents a distinct disease phenotype with increased mortality. HPV−positive (HPV+) and HPV− CC demonstrate different molecular pathology, prognosis, and response to treatment. Furthermore, CC caused by HPV α9 types (HPV16-like) often have better outcomes than those caused by HPV α7 types (HPV18-like). This study systematically and comprehensively compared the expression of genes involved in major histocompatibility complex (MHC) class I and II presentation within CC caused by HPV α9 types, HPV α7 types, and HPV− CC. We observed increased expression of MHC class I and II classical and non-classical genes in HPV+ CC and overall higher expression of genes involved in their antigen loading and presentation apparatus as well as transcriptional regulation. Increased expression of MHC I-related genes differs from previous studies using cell culture models. These findings identify crucial differences between antigen presentation within the tumor immune microenvironments of HPV+ and HPV− CC, as well as modest differences between HPV α9 and α7 CC. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers. Full article
(This article belongs to the Special Issue Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis)
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14 pages, 1532 KiB  
Article
The Diagnostic Value of Circulating Cell-Free HPV DNA in Plasma from Cervical Cancer Patients
by Sara Bønløkke, Magnus Stougaard, Boe Sandahl Sorensen, Berit Bargum Booth, Estrid Høgdall, Gitte-Bettina Nyvang, Jacob Christian Lindegaard, Jan Blaakær, Jesper Bertelsen, Katrine Fuglsang, Mikael Lenz Strube, Suzan Lenz and Torben Steiniche
Cells 2022, 11(14), 2170; https://doi.org/10.3390/cells11142170 - 11 Jul 2022
Cited by 13 | Viewed by 2460
Abstract
Circulating cell-free HPV DNA (ccfHPV DNA) may serve as a marker for cervical cancer. In this study, we used digital droplet PCR (ddPCR) to detect and quantify ccfHPV DNA in plasma from patients with HPV16- or HPV18-associated cervical cancer. Blood samples from 60 [...] Read more.
Circulating cell-free HPV DNA (ccfHPV DNA) may serve as a marker for cervical cancer. In this study, we used digital droplet PCR (ddPCR) to detect and quantify ccfHPV DNA in plasma from patients with HPV16- or HPV18-associated cervical cancer. Blood samples from 60 patients diagnosed with cervical cancer (FIGO IA1-IVA) at Aarhus or Odense University Hospital (June 2018 to March 2020) were collected prior to treatment, and patients were subdivided into an early stage (n = 30) and a late-stage subgroup (n = 30) according to disease stage. Furthermore, blood samples from eight women with HPV16- or 18-associated premalignant conditions (CIN3), and 15 healthy controls were collected. ddPCR was used to analyze plasma from all participants. ccfHPV DNA was detected in 19 late-stage patients (63.33%), 3 early stage patients (10.00%), and none of the CIN3 patients or controls. Quantitative evaluation showed significant correlations between ccfHPV DNA level and stage, tumor score, and tumor size. Thus, our results indicate that ccfHPV DNA may not be a useful marker for early detection of cervical cancer. However, for patients with advanced stage cervical cancer, ccfHPV DNA level represents a promising tool to establish tumor burden, making it useful for establishing treatment response and monitoring the disease. Full article
(This article belongs to the Special Issue Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis)
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Review

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29 pages, 15807 KiB  
Review
Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers
by Andrea Jazmín Chiliquinga, Brenda Acosta, Ingrid Ogonaga-Borja, Fernanda Villarruel-Melquiades, Jaime de la Garza, Patricio Gariglio, Rodolfo Ocádiz-Delgado, Ana Ramírez, Yesennia Sánchez-Pérez, Claudia M. García-Cuellar, Cecilia Bañuelos and Javier Camacho
Cells 2023, 12(10), 1376; https://doi.org/10.3390/cells12101376 - 12 May 2023
Cited by 1 | Viewed by 2262
Abstract
The human papilloma virus (HPV) group comprises approximately 200 genetic types that have a special affinity for epithelial tissues and can vary from producing benign symptoms to developing into complicated pathologies, such as cancer. The HPV replicative cycle affects various cellular and molecular [...] Read more.
The human papilloma virus (HPV) group comprises approximately 200 genetic types that have a special affinity for epithelial tissues and can vary from producing benign symptoms to developing into complicated pathologies, such as cancer. The HPV replicative cycle affects various cellular and molecular processes, including DNA insertions and methylation and relevant pathways related to pRb and p53, as well as ion channel expression or function. Ion channels are responsible for the flow of ions across cell membranes and play very important roles in human physiology, including the regulation of ion homeostasis, electrical excitability, and cell signaling. However, when ion channel function or expression is altered, the channels can trigger a wide range of channelopathies, including cancer. In consequence, the up- or down-regulation of ion channels in cancer makes them attractive molecular markers for the diagnosis, prognosis, and treatment of the disease. Interestingly, the activity or expression of several ion channels is dysregulated in HPV-associated cancers. Here, we review the status of ion channels and their regulation in HPV-associated cancers and discuss the potential molecular mechanisms involved. Understanding the dynamics of ion channels in these cancers should help to improve early diagnosis, prognosis, and treatment in the benefit of HPV-associated cancer patients. Full article
(This article belongs to the Special Issue Molecular and Immunological Mechanisms of HPV-Induced Carcinogenesis)
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