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

Chakravarthy, Ankur, Reddin, Ian, Henderson, Stephen, Dong, Cindy, Kirkwood, Nerissa, Jeyakumar, Maxmilan, Rodriguez, Daniela Rothschild, Martinez, Natalia Gonzalez, McDermott, Jacqueline, Su, Xiaoping, and others. (2022) Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nature Communications, 13 (1). Article Number 5818. ISSN 2041-1723. (doi:10.1038/s41467-022-33544-x) (KAR id:97465)

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Official URL: https://doi.org/10.1038/s41467-022-33544-x

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.

Item Type:	Article
DOI/Identification number:	10.1038/s41467-022-33544-x
Additional information:	For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords:	HPV, cancer, HPV16, HPV18, oncology, CSCC, cervical cancer, prognosis
Subjects:	Q Science
Divisions:	Divisions > Division of Natural Sciences > Centre for Interdisciplinary Studies of Reproduction Divisions > Division of Natural Sciences > Biosciences
Funders:	Rosetrees Trust (https://ror.org/04e3zg361) Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982) Royal Society (https://ror.org/03wnrjx87) Medical Research Council (https://ror.org/03x94j517) Cancer Research UK (https://ror.org/054225q67)
Depositing User:	Peter Ellis
Date Deposited:	17 Oct 2022 08:02 UTC
Last Modified:	04 Mar 2024 16:24 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/97465 (The current URI for this page, for reference purposes)

University of Kent Author Information

Dong, Cindy.

Creator's ORCID:
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Jeyakumar, Maxmilan.

Creator's ORCID:
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Ellis, Peter J.I..

Creator's ORCID:	https://orcid.org/0000-0001-9709-7934
CReDIT Contributor Roles:

Wass, Mark N..

Creator's ORCID:	https://orcid.org/0000-0001-5428-6479
CReDIT Contributor Roles:

Michaelis, Martin.

Creator's ORCID:	https://orcid.org/0000-0002-5710-5888
CReDIT Contributor Roles:

Fenton, Tim R..

Creator's ORCID:	https://orcid.org/0000-0002-4737-8233
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