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Background <p>Scarce data exist on host gene methylation in oropharyngeal squamous cell carcinomas (OPCs), which are caused by human papillomavirus (HPV) in approximately 40% of cases. We analyzed the methylation status of two host genes involved in cervical carcinogenesis, <i>FAM19A4</i> and <i>miR124-2</i>, in formalin-fixed paraffin-embedded (FFPE) tissues of primary HPV-driven OPCs (i.e., HPV-positive and p16INK4A-positive), HPV-negative OPCs, head and neck (HN) squamous cell papillomas, and oral rinse-and-gargles (ORGs) from individuals without HN lesions.</p> Methods <p>A multiplex real-time methylation-specific PCR on bisulfite-converted DNA was employed (PreCursor-M+, Fujirebio). Hypermethylation for each target was expressed as negative/positive based on the ΔΔCt, as well as by the ΔΔCt ratio (2<sup>-ΔΔCt</sup>).</p> Results <p>A total of 70 HPV-driven OPCs (66 HPV16+, 94.3%), 71 HPV-negative OPCs, 12 HN papillomas, and 20 ORGs were evaluated. Six of the 153 FFPE-purified DNA samples (3.9%) yielded invalid results. Hypermethylation for at least one target gene was observed in 56 of 69 valid HPV-driven OPCs (81.2%) and 33 of 67 valid HPV-negative OPCs (49.2%; <i>p</i> &lt; 0.0001). None of the papillomas or ORGs were hypermethylated. HPV-driven OPCs showed a significantly higher methylation level compared with HPV-negative OPCs for both <i>FAM19A4</i> (median ΔΔCt ratio 11.95 vs. 5.49; <i>p</i> = 0.0001) and <i>miR124-2</i> (median ΔΔCt ratio 15.65 vs. 8.27; <i>p</i> &lt; 0.0001).</p> Conclusions <p>Our findings indicate that <i>FAM19A4</i>/<i>miR124-2</i> hypermethylation occurs exclusively in tumor samples and that methylation levels are significantly higher in HPV-driven OPCs than in HPV-negative OPCs.</p>

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FAM19A4 and miR124-2 methylation status in human papillomavirus-driven and human papillomavirus-negative oropharyngeal squamous cell carcinomas

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月15日

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  • Maria Gabriella Donà,
  • Eugenia Giuliani,
  • Valentina Laquintana,
  • Renato Covello,
  • Raul Pellini,
  • Silvia Moretto,
  • Alessandra Latini,
  • Maria Benevolo,
  • Francesca Rollo

摘要

Background

Scarce data exist on host gene methylation in oropharyngeal squamous cell carcinomas (OPCs), which are caused by human papillomavirus (HPV) in approximately 40% of cases. We analyzed the methylation status of two host genes involved in cervical carcinogenesis, FAM19A4 and miR124-2, in formalin-fixed paraffin-embedded (FFPE) tissues of primary HPV-driven OPCs (i.e., HPV-positive and p16INK4A-positive), HPV-negative OPCs, head and neck (HN) squamous cell papillomas, and oral rinse-and-gargles (ORGs) from individuals without HN lesions.

Methods

A multiplex real-time methylation-specific PCR on bisulfite-converted DNA was employed (PreCursor-M+, Fujirebio). Hypermethylation for each target was expressed as negative/positive based on the ΔΔCt, as well as by the ΔΔCt ratio (2-ΔΔCt).

Results

A total of 70 HPV-driven OPCs (66 HPV16+, 94.3%), 71 HPV-negative OPCs, 12 HN papillomas, and 20 ORGs were evaluated. Six of the 153 FFPE-purified DNA samples (3.9%) yielded invalid results. Hypermethylation for at least one target gene was observed in 56 of 69 valid HPV-driven OPCs (81.2%) and 33 of 67 valid HPV-negative OPCs (49.2%; p < 0.0001). None of the papillomas or ORGs were hypermethylated. HPV-driven OPCs showed a significantly higher methylation level compared with HPV-negative OPCs for both FAM19A4 (median ΔΔCt ratio 11.95 vs. 5.49; p = 0.0001) and miR124-2 (median ΔΔCt ratio 15.65 vs. 8.27; p < 0.0001).

Conclusions

Our findings indicate that FAM19A4/miR124-2 hypermethylation occurs exclusively in tumor samples and that methylation levels are significantly higher in HPV-driven OPCs than in HPV-negative OPCs.