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Updated: Jun 27, 2025

Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis
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Published on: June 14, 2019

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HPV DNA Integration at Actionable Cancer-Related Genes Loci in HPV-Associated Carcinomas

Xavier Sastre-Garau1, Lilia Estrada-Virrueta2, François Radvanyi2

  • 1Department of Pathology, Centre Hospitalier Intercommunal de Créteil, 40, Avenue de Verdun, 94010 Créteil, France.

Cancers
|April 27, 2024
PubMed

Insights

Human papillomavirus (HPV) integration into host DNA frequently targets cancer-related genes, especially in highly recurrent events. These HPV-targeted genes represent promising therapeutic targets for HPV-associated cancers.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Human papillomavirus (HPV) infection is a major cause of various carcinomas.
  • Viral integration into the host genome can alter cancer-related genes, presenting potential therapeutic targets.
  • Quantitative assessments of these integration events, particularly for less frequent targets, are lacking.

Purpose of the Study:

  • To quantitatively assess host DNA sequences targeted by HPV integration in HPV-associated cancers.
  • To identify and characterize cancer-related genes and potential therapeutic targets affected by viral insertion.
  • To investigate the relationship between HPV genotypes, tumor localization, and targeted gene recurrence.

Main Methods:

  • Construction and analysis of a database comprising 1455 HPV-associated carcinoma cases.
  • Classification of host DNA integration sites into non-recurrent, weakly recurrent, and highly recurrent categories.
  • Comparison of cancer-related gene targeting rates between different recurrence categories and HPV genotypes.
  • Analysis of druggable targets among HPV-integrated genes using literature and DepMap database.

Main Results:

  • A significant increase in cancer-related gene targeting was observed with increasing recurrence of HPV integration sites (6.5% non-recurrent to 40.1% highly recurrent).
  • High-risk HPV genotypes (16/18/45) were associated with a higher rate of cancer-related gene targeting.
  • Approximately 30.2% of all targeted genes were druggable, rising to 50% in highly recurrent targets.
  • Genes targeted by viral insertion emerged as potential candidates in HPV-driven oncogenesis.

Conclusions:

  • HPV integration events disproportionately target cancer-related genes, with a strong correlation between recurrence frequency and the likelihood of targeting such genes.
  • A substantial proportion of HPV-targeted genes are druggable, highlighting their therapeutic potential.
  • Systematic characterization of HPV/host fusion sequences is crucial for understanding HPV-driven carcinogenesis and developing personalized treatments.
Keywords:
HPVHPV DNA integrationtherapeutic targetviral oncogenesis

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