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

Author:

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,Halle Mari Kyllesø,Krakstad Camilla,Soleiman Afschin,Sprung Susanne,Ellis Peter,Wass Mark,Michaelis Martin,Lyng Heidi,Fiegl Heidi,Salvesen Helga,Thomas Gareth,Doorbar John,Chester Kerry,Feber Andrew,Fenton Tim RORCID

Abstract

AbstractHuman papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

Publisher

Cold Spring Harbor Laboratory

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