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Updated: Feb 7, 2026

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
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A Three-subtype Molecular model of Cervical Cancer: Multiple PI3K Pathway inhibitors suppress growth and cooperate

Hong Lou1, David Langan2, Nick Syracuse3

  • 1Cancer Genetics Research Laboratory, Division of Cancer Epidemiology and Genetics, Frederick National Laboratory for Cancer Research, Gaithersburg, MD USA.

Medrxiv : the Preprint Server for Health Sciences
|February 6, 2026
PubMed
Abstract

Insights

This study defines three molecular subtypes of cervical cancer (CC) based on PIK3CA and YAP1 status. PI3K inhibitors show promise in targeting PIK3CA-mutant CC and may enhance immune therapies for advanced HPV16 cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Cervical cancer (CC) is primarily caused by human papillomavirus (HPV) infections.
  • Lack of molecularly defined subtypes and targeted therapies hinders effective treatment.
  • Understanding molecular alterations is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To define molecular subtypes of cervical cancer.
  • To evaluate the efficacy of targeted agents, specifically PI3K inhibitors, against defined subtypes.
  • To explore the potential of combining targeted therapies with immune-based treatments.

Main Methods:

  • Analysis of public datasets to identify molecular subtypes.
  • In vitro drug treatment of cervical cancer cell lines with PI3K and pan-AKT inhibitors.
  • Assessment of T cell proliferation and cytotoxicity in response to targeted agents.

Main Results:

  • Three molecular subtypes were identified: PIK3CA wild-type/no YAP1 amplification, PIK3CA mutation/no YAP1 amplification, and PIK3CA wild-type/YAP1 amplification.
  • YAP1-amplified cervical cancer is associated with poorer patient survival.
  • PI3K inhibitors (Alpelisib, Inavolisib) selectively inhibited PIK3CA-mutated cell lines.
  • Alpelisib demonstrated inhibition of HPV16 E7 oncoprotein, CD274/PD-L1, YAP1, and EGFR in PI3K-mutated cells.
  • Combination therapy with Alpelisib and donor T cells enhanced anti-cancer cytotoxicity.

Conclusions:

  • Targeted inhibitors effectively target PIK3CA-mutant cervical cancer.
  • Combining PI3K inhibitors with immune therapies may improve outcomes for advanced HPV16-positive cervical cancer.
  • Further investigation into targeted therapies is essential for improving patient prognosis.
Keywords:
Cervical CancerImmune Checkpoint InhibitorImmunotherapyMajor histocompatibility complex - MHCVirologyclinical outcomesreal-world data

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