Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Human Papillomavirus from Lab to Life: Insights from Molecular Researches

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 25929

Share This Special Issue

Special Issue Editor

Dr. Marta del Pino

E-Mail Website
Guest Editor

1. Gynecology Oncology Unit, Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic, 08036 Barcelona, Spain
2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona, Barcelona, Spain
Interests: HPV; CIN; VIN; AIN; prognosis; genotyping; p16; dual staining; HPV-vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human Papillomavirus (HPV) affects a significant part of the population worldwide. Although the immunological system is usually able to clear the virus, some infections persist inducing a broad spectrum of cell abnormalities that range from benign proliferations to premalignant lesions at risk of progression to cancer. Approximately 4.5% (640,000 cases) of all new cancers diagnosed yearly worldwide are caused by persistent HPV infection. Despite an impressive amount of information on HPV infection has become available the last years, several gaps still remain regarding HPV disease.

Cervical cancer is one of the most common cancers in women worldwide. HPV infection of cervical epithelium with high-risk (hr-)HPV might result in productive or transforming cervical intraepithelial neoplasia (CIN) lesions, the morphology of which can overlap. On the basis of (epi)genetic changes and aberrations in host-cell genes, early and advanced transforming CIN lesions a risk of progression can be distinguished. The characterization of the transforming infections is a priority in the current landscape of cervical disease, since the identification of HPV positive women at higher risk of premalignancies in the newly introduced HPV-based screening strategies (triage) is fundamental.

Finally, in recent years, we have observed an exponential increase of other HPV-related cancers such as head and neck, anal or vulvar cancers, especially in high-income countries. The natural history and the molecular pathways behind the development of these HPV-associated cancers still remains poorly understood.

In this special issue we look forward promoting and recognizing research on HPV and HPV-associated diseases, focusing on molecular studies. We are calling for manuscripts dealing with biomarkers improving the identification of HPV-associated disease, prognostic markers and strategies of triage for HPV positive women. We aim to provide a broad overview of the ongoing research in the HPV world.

Dr. Marta del Pino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

biomarkers (DNA, mRNA, E6, E7, E4, p16, Ki67, miRNA, methylation, genotyping...)
triage
HPV vaccines
prognosis

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

20 pages, 25014 KiB

Open AccessArticle

K-Mer Analyses Reveal Different Evolutionary Histories of Alpha, Beta, and Gamma Papillomaviruses

by Zigui Chen, Filippo Utro, Daniel Platt, Rob DeSalle, Laxmi Parida, Paul K. S. Chan and Robert D. Burk

Int. J. Mol. Sci. 2021, 22(17), 9657; https://doi.org/10.3390/ijms22179657 - 06 Sep 2021

Cited by 10 | Viewed by 2789

Abstract

Papillomaviruses (PVs) are a heterogeneous group of DNA viruses that can infect fish, birds, reptiles, and mammals. PVs infecting humans (HPVs) phylogenetically cluster into five genera (Alpha-, Beta-, Gamma-, Mu- and Nu-PV), with differences in tissue tropism and carcinogenicity. The evolutionary features associated with the divergence of Papillomaviridae are not well understood. Using a combination of k-mer distributions, genetic metrics, and phylogenetic algorithms, we sought to evaluate the characteristics and differences of Alpha-, Beta- and Gamma-PVs constituting the majority of HPV genomes. A total of 640 PVs including 442 HPV types, 27 non-human primate PV types, and 171 non-primate animal PV types were evaluated. Our analyses revealed the highest genetic diversity amongst Gamma-PVs compared to the Alpha and Beta PVs, suggesting reduced selective pressures on Gamma-PVs. Using a sequence alignment-free trimer (k = 3) phylogeny algorithm, we reconstructed a phylogeny that grouped most HPV types into a monophyletic clade that was further split into three branches similar to alignment-based classifications. Interestingly, a subset of low-risk Alpha HPVs (the species Alpha-2, 3, 4, and 14) split from other HPVs and were clustered with non-human primate PVs. Surprisingly, the trimer-constructed phylogeny grouped the Gamma-6 species types originally isolated from the cervicovaginal region with the main Alpha-HPV clade. These data indicate that characterization of papillomavirus heterogeneity via orthogonal approaches reveals novel insights into the biological understanding of HPV genomes. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

15 pages, 1720 KiB

Open AccessArticle

Genetic and Epigenetic Variations of HPV52 in Cervical Precancer

by Katharine J. Bee, Ana Gradissimo, Zigui Chen, Ariana Harari, Mark Schiffman, Tina Raine-Bennett, Philip E. Castle, Megan Clarke, Nicolas Wentzensen and Robert D. Burk

Int. J. Mol. Sci. 2021, 22(12), 6463; https://doi.org/10.3390/ijms22126463 - 16 Jun 2021

Cited by 9 | Viewed by 2631

Abstract

The goal of this study was to identify human papillomavirus (HPV) type 52 genetic and epigenetic changes associated with high-grade cervical precancer and cancer. Patients were selected from the HPV Persistence and Progression (PaP) cohort, a cervical cancer screening program at Kaiser Permanente Northern California (KPNC). We performed a nested case-control study of 89 HPV52-positive women, including 50 cases with predominantly cervical intraepithelial neoplasia grade 3 (CIN3) and 39 controls without evidence of abnormalities. We conducted methylation analyses using Illumina sequencing and viral whole genome Sanger sequencing. Of the 24 CpG sites examined, increased methylation at CpG site 5615 in HPV52 L1 region was the most significantly associated with CIN3, with a difference in median methylation of 17.9% (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.9–11.8) and an area under the curve of 0.73 (AUC; 95% CI = 0.62–0.83). Complete genomic sequencing of HPV52 isolates revealed associations between SNPs present in sublineage C2 and a higher risk of CIN3, with ORs ranging from 2.8 to 3.3. This study identified genetic and epigenetic HPV52 variants associated with high risk for cervical precancer, improving the potential for early diagnosis of cervical neoplasia caused by HPV52. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

20 pages, 5599 KiB

Open AccessArticle

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions

by María Lourdes Garza-Rodríguez, Mariel Araceli Oyervides-Muñoz, Antonio Alí Pérez-Maya, Celia Nohemí Sánchez-Domínguez, Anais Berlanga-Garza, Mauro Antonio-Macedo, Lezmes Dionicio Valdés-Chapa, Diego Vidal-Torres, Oscar Vidal-Gutiérrez, Diana Cristina Pérez-Ibave and Víctor Treviño

Int. J. Mol. Sci. 2021, 22(6), 3242; https://doi.org/10.3390/ijms22063242 - 22 Mar 2021

Cited by 7 | Viewed by 2380

Abstract

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

12 pages, 15345 KiB

Open AccessArticle

Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers

by Rüveyda Dok, Mary Glorieux, Marieke Bamps and Sandra Nuyts

Int. J. Mol. Sci. 2021, 22(4), 1504; https://doi.org/10.3390/ijms22041504 - 03 Feb 2021

Cited by 14 | Viewed by 2229

Abstract

Radiotherapy (RT) has a central role in head and neck squamous cell carcinoma (HNSCC) treatment. Targeted therapies modulating DNA damage response (DDR) and more specific cell cycle checkpoints can improve the radiotherapeutic response. Here, we assessed the influence of ataxia-telangiectasia mutated and Rad3-related (ATR) inhibition with the ATR inhibitor AZD6738 on RT response in both human papillomavirus (HPV)-negative and HPV-positive HNSCC. We found that ATR inhibition enhanced RT response in HPV-negative and HPV-positive cell lines independent of HPV status. The radiosensitizing effect of AZD6738 was correlated with checkpoint kinase 1 (CHK1)-mediated abrogation of G2/M-arrest. This resulted in the inhibition of RT-induced DNA repair and in an increase in the percentage of micronucleated cells. We validated the enhanced RT response in HPV-negative and HPV-positive xenograft models. These data demonstrate the potential use of ATR inhibition in combination with RT as a treatment option for both HPV-negative and HPV-positive HNSCC patients. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

13 pages, 4456 KiB

Open AccessArticle

p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases

by Natalia Rakislova, Laia Alemany, Omar Clavero, Adela Saco, Aureli Torné, Marta del Pino, Meritxell Munmany, Maria Teresa Rodrigo-Calvo, José Guerrero, Lorena Marimon, Naiara Vega, Beatriz Quirós, Belen Lloveras, Inmaculada Ribera-Cortada, Maria Alejo, Michael Pawlita, Wim Quint, Silvia de Sanjose, Jaume Ordi and VVAP Study Group

Int. J. Mol. Sci. 2020, 21(21), 8091; https://doi.org/10.3390/ijms21218091 - 29 Oct 2020

Cited by 20 | Viewed by 6082

Abstract

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

Review

Jump to: Research

26 pages, 8897 KiB

Open AccessReview

Advances in Targeting HPV Infection as Potential Alternative Prophylactic Means

by Sinead Carse, Martina Bergant and Georgia Schäfer

Int. J. Mol. Sci. 2021, 22(4), 2201; https://doi.org/10.3390/ijms22042201 - 23 Feb 2021

Cited by 11 | Viewed by 5653

Abstract

Infection by oncogenic human papillomavirus (HPV) is the primary cause of cervical cancer and other anogenital cancers. The majority of cervical cancer cases occur in low- and middle- income countries (LMIC). Concurrent infection with Human Immunodeficiency Virus (HIV) further increases the risk of HPV infection and exacerbates disease onset and progression. Highly effective prophylactic vaccines do exist to combat HPV infection with the most common oncogenic types, but the accessibility to these in LMIC is severely limited due to cost, difficulties in accessing the target population, cultural issues, and maintenance of a cold chain. Alternative preventive measures against HPV infection that are more accessible and affordable are therefore also needed to control cervical cancer risk. There are several efforts in identifying such alternative prophylactics which target key molecules involved in early HPV infection events. This review summarizes the current knowledge of the initial steps in HPV infection, from host cell-surface engagement to cellular trafficking of the viral genome before arrival in the nucleus. The key molecules that can be potentially targeted are highlighted, and a discussion on their applicability as alternative preventive means against HPV infection, with a focus on LMIC, is presented. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Figure 1

14 pages, 976 KiB

Open AccessReview

HPV Meets APOBEC: New Players in Head and Neck Cancer

by Giuseppe Riva, Camilla Albano, Francesca Gugliesi, Selina Pasquero, Sergio Fernando Castillo Pacheco, Giancarlo Pecorari, Santo Landolfo, Matteo Biolatti and Valentina Dell’Oste

Int. J. Mol. Sci. 2021, 22(3), 1402; https://doi.org/10.3390/ijms22031402 - 30 Jan 2021

Cited by 23 | Viewed by 3265

Abstract

Besides smoking and alcohol, human papillomavirus (HPV) is a factor promoting head and neck squamous cell carcinoma (HNSCC). In some human tumors, including HNSCC, a number of mutations are caused by aberrantly activated DNA-modifying enzymes, such as the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. As the enzymatic activity of APOBEC proteins contributes to the innate immune response to viruses, including HPV, the role of APOBEC proteins in HPV-driven head and neck carcinogenesis has recently gained increasing attention. Ongoing research efforts take the cue from two key observations: (1) APOBEC expression depends on HPV infection status in HNSCC; and (2) APOBEC activity plays a major role in HPV-positive HNSCC mutagenesis. This review focuses on recent advances on the role of APOBEC proteins in HPV-positive vs. HPV-negative HNSCC. Full article

(This article belongs to the Special Issue Human Papillomavirus from Lab to Life: Insights from Molecular Researches)

► Show Figures

Journal Menu

Journal Browser

Human Papillomavirus from Lab to Life: Insights from Molecular Researches

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI