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Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance

Author

Listed:
  • Ankur Chakravarthy

    (University Health Network)

  • Ian Reddin

    (University of Southampton)

  • Stephen Henderson

    (University College London)

  • Cindy Dong

    (University of Kent)

  • Nerissa Kirkwood

    (University of Kent)

  • Maxmilan Jeyakumar

    (University of Kent)

  • Daniela Rothschild Rodriguez

    (University of Kent)

  • Natalia Gonzalez Martinez

    (University of Kent)

  • Jacqueline McDermott

    (University College London)

  • Xiaoping Su

    (MD Anderson Cancer Center)

  • Nagayasau Egawa

    (University of Cambridge)

  • Christina S. Fjeldbo

    (Oslo University Hospital)

  • Vilde Eide Skingen

    (Oslo University Hospital)

  • Heidi Lyng

    (Oslo University Hospital
    University of Oslo)

  • Mari Kyllesø Halle

    (University of Bergen)

  • Camilla Krakstad

    (University of Bergen)

  • Afschin Soleiman

    (Tirol Kliniken Innsbruck)

  • Susanne Sprung

    (Medical University of Innsbruck)

  • Matt Lechner

    (University College London)

  • Peter J. I. Ellis

    (University of Kent)

  • Mark Wass

    (University of Kent)

  • Martin Michaelis

    (University of Kent)

  • Heidi Fiegl

    (Medical University of Innsbruck)

  • Helga Salvesen

    (University of Bergen)

  • Gareth J. Thomas

    (University of Southampton)

  • John Doorbar

    (University of Cambridge)

  • Kerry Chester

    (University College London)

  • Andrew Feber

    (Royal Marsden Hospital Trust
    University College London)

  • Tim R. Fenton

    (University of Southampton
    University of Kent
    University of Southampton)

Abstract

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of the STK11 tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

Suggested Citation

  • Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33544-x
    DOI: 10.1038/s41467-022-33544-x
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    1. Manuel Rodrigues & Giulia Vanoni & Pierre Loap & Coraline Dubot & Eleonora Timperi & Mathieu Minsat & Louis Bazire & Catherine Durdux & Virginie Fourchotte & Enora Laas & Nicolas Pouget & Zahra Castel, 2023. "Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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