Skip to main content
SMFM 2024 Pregnancy Meeting Main banner
Final Program


Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Presentation Icons
Additional registration fee required
Additional registration fee required
Faculty have requested this content not be shared on social media
Faculty have requested this content not be shared on social media
CME Credit Offered
CME Credit Offered
Poster Icons
Foundation Awardee
Foundation Awardee
No Social Media
No Social Media
Back
Q&A

Infectious Diseases

Poster Session 4

(939) Stages of HPV Cervical Cancer Discerned by Integrated Host-viral Single-cell and Spatial Biology

Wednesday, February 14, 2024
1:00 PM – 2:30 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level

    Coauthor(s)

  • KT

    Khanh L. Tran, BS

    Baylor College of Medicine and Texas Children’s Hospital
    Houston, TX, United States

  • David N. Moorshead, BS

    Mr.
    Baylor College of Medicine and Texas Children’s Hospital
    Houston, TX, United States

  • MZ

    Maryshe Zeitsman, BS

    Baylor College of Medicine and Texas Children’s Hospital
    Houston, TX, United States

  • Michael D. Jochum, Jr., PhD

    Postdoctoral Research Associate
    Baylor College of Medicine
    Houston, TX, United States

  • Kjersti M. Aagaard, MD, PhD

    Professor and Vice Chair of Research Department of Obstetrics and Gynecology, Division of MFM
    Texas Children's Hospital, Baylor College of Medicine
    Houston, TX, United States

    • Primary & Presenting Author(s)

  • Enrico R. Barrozo, PhD

    Baylor College of Medicine and Texas Children’s Hospital
    Houston, TX, United States

Objective: Cervical cancer damages cervical integrity and may necessitate invasive surgical procedures that negatively impact the likelihood of future successful pregnancies. Over 99% of cervical cancer cases are associated with human papillomavirus (HPV). The temporal transition and spatial distribution of cellular subsets during cervical cancer progression provide valuable insights into HPV disease development. A recent study examined HPV-induced malignant transformation and immune remodeling with single-cell and spatial transcriptomics. However, viral gene expression was not directly assessed. Therefore, we hypothesized that host immune response programs successfully restrict, or fail to control, HPV gene expression in the cervix, ultimately correlating with cancer progression.

Study Design:

To address this hypothesis, we analyzed the single-cell and spatial transcriptomics data from HPV+ subjects with known clinical phenotypes (n= 9;) and aligned them to our custom HPV16 and human reference.


Results: Out of the 88,743 total single-cell and spatial transcriptomes yielded 16 cell types and spatial niches, and we detected 4,710 transcriptomes with HPV gene expression (Fig. 1A). We identified 2,883 significant DEGs (Fig. 1B; q< 0.05) associated with controlling (28% of DEGs), or failing to control (72%), HPV. HPV gene expression correlated with high-grade intraepithelial lesions, specifically in a subset of epithelial cells. Host gene expression was significantly perturbed in a cervical cancer specimen and negatively correlated with HPV transcription (Fig. 1C). Restriction of HPV gene expression correlated with normal and cervical cancer phenotypes, and the gene signatures aligned with immune cell populations (Fig. 1D). Specifically, cervical cancer outcomes were associated with the B-to-plasma cell transition.

Conclusion: By integrative host-viral analyses, we identified gene signatures that may lead to potentially novel targets for therapeutic strategies combating HPV persistence and cervical cancer progression, which in turn may positively impact future pregnancies.