Potential Therapeutic Targets and Non-invasive Procedures for Improving the Treatment and Follow-Up of HPV-Associated Malignancies

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

Deadline for manuscript submissions: 15 June 2024 | Viewed by 992

Special Issue Editor


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Guest Editor
Department of Pathology, Hôpital Intercommunal de Créteil 40, Avenue de Verdun, 94010 Créteil, France
Interests: gynecological tumors; cervical cancer; human papillomaviruses; viral oncogenesis; ovarian cancers; head and neck cancers

Special Issue Information

Dear Colleagues,

The identification of specific genotypes of human papillomaviruses (HPVs) as the main etiologic factors of anogenital neoplasia and a large proportion of carcinomas of the head and neck is well established. This knowledge has contributed to the development of an efficient prophylactic policy based on the use of HPV vaccines directed against these genotypes. However, the population of patients who are not able to benefit from vaccination remains high, and invasive carcinomas associated with HPVs are a huge burden in many countries. The role of viral oncogenes in the tumor process has been well documented, but, although the acquired knowledge on the biology of HPVs has permitted the implementation of a coherent approach to reducing the frequency of persistent HPV infections, no original therapy of HPV-associated carcinomas specifically directed against viral targets or virally altered pathways has been developed to date. This contrasts with the impressive efficiency of immunotherapies or original approaches based on the targeting of specific molecular motives developed in other tumor types. Furthermore, circulating HPV DNA as a tumor marker should serve as a model for the development of clinical applications for the detection of ct-DNA in solid tumors.

In order to review the potential development of innovative therapeutic approaches in HPV-associated carcinoma, Cancers proposes a Special Issue focused on Potential Therapeutic Targets and Non-invasive Procedures for Improving Treatment and Follow-up of HPV-associated Malignancies. This Special Issue aims to document more particularly some of the following aspects:

  • To what extent does the HPV genome represent a rational therapeutic target in HPV-associated malignancies? In other terms, is the presence and/or the expression of the HPV genome necessary for the maintenance of the tumor state?
  • What is the potential of new approaches such as mRNAs or CRISPR/Cas9 for the treatment of patients with HPV-associated invasive carcinomas?
  • Immunotherapy has proven efficiency in the treatment of viral-associated tumors such as Merkel carcinoma associated with the Merkel Cell Polyomavirus (MCPyV). What are the perspectives of immunotherapy in the treatment of pre-invasive or invasive HPV-associated carcinomas?
  • Are there pathways recurrently altered via HPV in the tumor process that could correspond to druggable targets?
  • To what extent does HPV molecular characterization point to genetic alterations that may be used to improve the follow-up or treatment of patients with HPV-associated cancers?

We hope that this Special Issue will stimulate the consideration of potential therapeutic approaches offered by the presence of the oncogenic virus in HPV-associated neoplasia.

Dr. Xavier Sastre-Garau
Guest Editor

Manuscript Submission Information

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Keywords

  • therapeutic targets in HPV-associated cancers
  • HPV-targeted therapy
  • immunotherapy in HPV-associated carcinomas
  • circulating HPV DNA

Published Papers (1 paper)

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Research

16 pages, 3472 KiB  
Article
HPV DNA Integration at Actionable Cancer-Related Genes Loci in HPV-Associated Carcinomas
by Xavier Sastre-Garau, Lilia Estrada-Virrueta and François Radvanyi
Cancers 2024, 16(8), 1584; https://doi.org/10.3390/cancers16081584 - 20 Apr 2024
Viewed by 557
Abstract
In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built [...] Read more.
In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as “non-recurrent” (one single reported case; 838 loci), “weakly recurrent” (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci). Whereas the overall rate of cancer-related target genes was 3.3% in the Gencode database, this rate increased to 6.5% in “non-recurrent”, 11.4% in “weakly recurrent”, and 40.1% in “highly recurrent” genes targeted by integration (p = 4.9 × 10−4). This rate was also significantly higher in tumors associated with high-risk HPV16/18/45 than other genotypes. Among the genes targeted by HPV insertion, 30.2% corresponded to direct or indirect druggable targets, a rate rising to 50% in “highly recurrent” targets. Using data from the literature and the DepMap 23Q4 release database, we found that genes targeted by viral insertion could be new candidates potentially involved in HPV-associated oncogenesis. A more systematic characterization of HPV/host fusion DNA sequences in HPV-associated cancers should provide a better knowledge of HPV-driven carcinogenesis and favor the development of personalize patient treatments. Full article
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