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Silencing HPV: the rise of RNA therapeutics in cervical cancer

Samira Mohammadi Khorramabadi1,2,3, Nader Ebrahimi2, Parisa Shiri Aghbash3,4

  • 1Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran.

Infectious Agents and Cancer
|January 30, 2026
PubMed

Insights

RNA-based therapies show promise for treating cervical cancer by targeting human papillomaviruses (HPV). These novel treatments selectively silence HPV oncogenes, leading to cancer cell death and tumor regression in preclinical studies.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Cervical cancer persists globally despite HPV vaccination, primarily due to persistent high-risk human papillomavirus (HPV) infections.
  • HPV oncogenes E6 and E7 inactivate tumor suppressors p53 and Rb, driving cancer development.
  • Targeting these oncogenes presents a promising therapeutic strategy for HPV-positive cervical cancers.

Purpose of the Study:

  • To review the progress and potential of RNA-based therapeutic strategies for cervical cancer.
  • To highlight the mechanisms of RNA-mediated gene silencing and mRNA vaccination against HPV.
  • To discuss advancements in delivery systems, combination therapies, and genome editing for cervical cancer treatment.

Main Methods:

  • Review of preclinical and early-stage clinical studies on RNA-based therapeutics for cervical cancer.
  • Analysis of RNA interference (RNAi) techniques including small interfering RNA (siRNA), short hairpin RNA (shRNA), and antisense oligonucleotides (ASOs).
  • Evaluation of messenger RNA (mRNA) vaccine platforms targeting HPV E6/E7 oncogenes.

Main Results:

  • RNA-mediated E6/E7 suppression restores p53/Rb activity, inducing apoptosis/senescence and inhibiting tumor growth in preclinical models.
  • mRNA vaccines encoding E6/E7 elicit potent HPV T-cell responses and achieve tumor regression in animal studies.
  • Early-phase clinical trials are investigating novel mRNA vaccines for HPV-positive malignancies, often combined with immunotherapies.

Conclusions:

  • RNA-based therapeutics offer a novel approach to targeting cervical cancer by selectively silencing HPV oncogenes.
  • Significant progress has been made in preclinical and early clinical settings, demonstrating efficacy in animal models and initial patient studies.
  • Future directions include advanced delivery systems, combinatorial treatments, and genome editing to enhance therapeutic outcomes for cervical cancer.

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