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Special Issue "Human Papillomavirus from Lab to Life: Insights from Molecular Researches"

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 2020).

Special Issue Editor

Dr. Marta del Pino

Guest Editor
Gynecology Oncology Unit. Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic, 08036 Barcelona, Spain. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona, Spain
Interests: HPV, CIN, VIN, AIN, prognosis, genotyping, p16, dual staining, HPV-vaccines

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 papers will be 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 (4 papers)

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Research

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Open AccessArticle
Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers
Int. J. Mol. Sci. 2021, 22(4), 1504; https://doi.org/10.3390/ijms22041504 - 03 Feb 2021
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 [...] Read more.
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
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Open AccessArticle
p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases
Int. J. Mol. Sci. 2020, 21(21), 8091; https://doi.org/10.3390/ijms21218091 - 29 Oct 2020
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 [...] Read more.
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
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Review

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Open AccessReview
Advances in Targeting HPV Infection as Potential Alternative Prophylactic Means
Int. J. Mol. Sci. 2021, 22(4), 2201; https://doi.org/10.3390/ijms22042201 (registering DOI) - 23 Feb 2021
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 [...] Read more.
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
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Open AccessReview
HPV Meets APOBEC: New Players in Head and Neck Cancer
Int. J. Mol. Sci. 2021, 22(3), 1402; https://doi.org/10.3390/ijms22031402 - 30 Jan 2021
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 [...] Read more.
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
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