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

Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance
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.
2041-1723
Chakravarthy, Ankur
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Reddin, Ian
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Henderson, Stephen
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Dong, Cindy
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Kirkwood, Nerissa
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Jeyakumar, Maxmilan
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Rodriguez, Daniela Rothschild
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Martinez, Natalia Gonzalez
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McDermott, Jacqueline
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Su, Xiaoping
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Egawa, Nagayasau
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Fjeldbo, Christina S.
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Skingen, Vilde Eide
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Lyng, Heidi
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Halle, Mari Kyllesø
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Krakstad, Camilla
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Soleiman, Afschin
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Sprung, Susanne
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Lechner, Matt
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Ellis, Peter J.I.
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Wass, Mark
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Michaelis, Martin
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Fiegl, Heidi
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Salvesen, Helga
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Thomas, Gareth J
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Doorbar, John
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Chester, Kerry
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Feber, Andrew
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Fenton, Tim R.
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Chakravarthy, Ankur
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Reddin, Ian
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Henderson, Stephen
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Dong, Cindy
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Kirkwood, Nerissa
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Jeyakumar, Maxmilan
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Rodriguez, Daniela Rothschild
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Martinez, Natalia Gonzalez
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McDermott, Jacqueline
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Su, Xiaoping
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Egawa, Nagayasau
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Fjeldbo, Christina S.
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Skingen, Vilde Eide
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Lyng, Heidi
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Halle, Mari Kyllesø
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Krakstad, Camilla
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Soleiman, Afschin
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Sprung, Susanne
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Lechner, Matt
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Ellis, Peter J.I.
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Wass, Mark
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Michaelis, Martin
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Fiegl, Heidi
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Salvesen, Helga
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Thomas, Gareth J
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Doorbar, John
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Chester, Kerry
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Feber, Andrew
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Fenton, Tim R.
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Chakravarthy, Ankur, Reddin, Ian, Henderson, Stephen, Dong, Cindy, Kirkwood, Nerissa, Jeyakumar, Maxmilan, Rodriguez, Daniela Rothschild, Martinez, Natalia Gonzalez, McDermott, Jacqueline, Su, Xiaoping, Egawa, Nagayasau, Fjeldbo, Christina S., Skingen, Vilde Eide, Lyng, Heidi, Halle, Mari Kyllesø, Krakstad, Camilla, Soleiman, Afschin, Sprung, Susanne, Lechner, Matt, Ellis, Peter J.I., Wass, Mark, Michaelis, Martin, Fiegl, Heidi, Salvesen, Helga, Thomas, Gareth J, Doorbar, John, Chester, Kerry, Feber, Andrew and Fenton, Tim R. (2022) Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nature Communications, 13 (1), [5818]. (doi:10.1038/s41467-022-33544-x).

Record type: Article

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.

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e-pub ahead of print date: 15 September 2022
Published date: 7 October 2022
Additional Information: © 2022. The Author(s).

Identifiers

Local EPrints ID: 471587
URI: http://eprints.soton.ac.uk/id/eprint/471587
ISSN: 2041-1723
PURE UUID: 10558174-0c20-426a-b0c9-0dc05a1a08e3
ORCID for Ian Reddin: ORCID iD orcid.org/0000-0001-5478-7855
ORCID for Tim R. Fenton: ORCID iD orcid.org/0000-0002-4737-8233

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Date deposited: 14 Nov 2022 17:38
Last modified: 06 Jan 2023 03:05

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Contributors

Author: Ankur Chakravarthy
Author: Ian Reddin ORCID iD
Author: Stephen Henderson
Author: Cindy Dong
Author: Nerissa Kirkwood
Author: Maxmilan Jeyakumar
Author: Daniela Rothschild Rodriguez
Author: Natalia Gonzalez Martinez
Author: Jacqueline McDermott
Author: Xiaoping Su
Author: Nagayasau Egawa
Author: Christina S. Fjeldbo
Author: Vilde Eide Skingen
Author: Heidi Lyng
Author: Mari Kyllesø Halle
Author: Camilla Krakstad
Author: Afschin Soleiman
Author: Susanne Sprung
Author: Matt Lechner
Author: Peter J.I. Ellis
Author: Mark Wass
Author: Martin Michaelis
Author: Heidi Fiegl
Author: Helga Salvesen
Author: Gareth J Thomas
Author: John Doorbar
Author: Kerry Chester
Author: Andrew Feber
Author: Tim R. Fenton ORCID iD

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