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Identification of HPV16-p16INK4a mediated methylation in oral potentially malignant disorder

Maria Rosa Buenahora1, Gloria Inés Lafaurie2, Sandra J Perdomo3

  • 1Unit of Oral Clinical Epidemiology, School of Dentistry, El Bosque University, Bogotá, Colombia.

Epigenetics
|November 9, 2020
PubMed

Insights

Epigenetic changes, specifically DNA methylation, are altered in oral potentially malignant disorders (OPMD). Human papillomavirus (HPV) infection influences immune and cell cycle genes in OPMD.

Area of Science:

  • Epigenetics
  • Oral Oncology
  • Virology

Background:

  • Oral potentially malignant disorders (OPMD) represent a critical stage in oral cancer development.
  • Epigenetic modifications, such as DNA methylation, are increasingly recognized as key players in carcinogenesis.
  • The role of Human Papillomavirus (HPV), particularly HPV16, and its interaction with host epigenetic machinery in OPMD is not fully elucidated.

Purpose of the Study:

  • To investigate the involvement of epigenetic modulation, specifically DNA methylation, by HPV16 and p16INK4a in OPMD.
  • To compare DNA methylation profiles in OPMD samples with varying p16INK4a expression and HPV16 status.

Main Methods:

  • Reduced-representation bisulphite sequencing (RRBS-Seq) was employed to generate DNA methylation profiles.
  • Twelve OPMD samples were analyzed in triplicate, categorized by p16INK4a expression and HPV16 genotype (positive or negative).
  • Groups included: p16INK4a+/HPV16+, p16INK4a+/HPV16-, and p16INK4a-/HPV16-.

Main Results:

  • Fifty-four percent of differentially methylated regions (DMRs) were hypermethylated, and 46% were hypomethylated.
  • Increased methylation in OPMD was independent of HPV presence; however, HPV+ samples showed hypermethylation in NOTCH1, Interferon-gamma, and Interleukin-6 signaling pathways.
  • Hypomethylated genes in HPV-infected samples were associated with immune response pathways (TRAF3-IRF, RIG-I/MDA5, TRAF6-IRF7, TLR3/4, MyD88-independent cascade).
  • DMRs in OPMD involved 19 genes related to cell cycle regulation, immune system, and focal adhesion.
  • Aberrant methylation was observed in p16INK4a-positive samples, suggesting a role in cancer progression.

Conclusions:

  • Epigenetic alterations, particularly DNA methylation changes, are prevalent in OPMD.
  • HPV infection in OPMD modulates genes involved in immune response and cell cycle regulation.
  • Aberrant DNA methylation in p16INK4a-positive OPMD samples indicates its potential significance in oral cancer progression.
Keywords:
DNA-methylationOral potentially malignant disorderRRBShuman papilloma virusimmune system

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