Comprehensive molecular landscape of anal squamous cell carcinoma: analysis of tissue and liquid biopsies from 1844 patients
Anal squamous cell carcinoma (aSCC) is a rare, predominantly HPV-driven cancer with limited treatment options. This study aimed to define its genomic landscape, identify actionable targets (AT), and highlight the clinical value of molecular profiling-especially liquid biopsy (LB)-based on Gustave Roussy's (GR) experience. In this retrospective analysis, 1844 patients from the U.S. and France underwent tissue biopsy (TB, n = 1733) and/or LB (n = 140), analyzed using the FoundationOne®CDx or FoundationOne® Liquid CDx assays both comprehensive genomic profiling assays for solid tumors covering ~324 genes. Twenty-nine patients had paired TB/LB, and 44 LB patients formed the clinically annotated GR subgroup. HPV was detected in 86.6% of cases, predominantly HPV-16 (75.6%). High tumor mutational burden (≥10 mut/Mb) was found in 17.1% of patients; microsatellite instability was rare (1.7%). Frequent mutations included PIK3CA (34.5%), KMT2D (18.0%), PTEN (13.1%), FBXW7 (12.9%), and TP53 (12.0%). ATs were identified in BRCA1/2, FGFR2/3, EGFR, KRAS, BRAF, and NRAS. Mutation patterns varied by HPV subtype. LB showed high concordance with TB, including HPV detection. At GR, LB informed treatment decisions in 18.2% of cases. Four clinical examples illustrated LB-guided therapies. This largest-to-date aSCC cohort reinforces molecular profiling-especially LB-as a key tool for guiding personalized therapy.
Authors
- Léonor Benhaïm (ORCID: https://orcid.org/0000-0003-3948-4156)
- Elena Fernández de Sevilla
- Cristina Smolenschi (ORCID: https://orcid.org/0000-0002-7568-6196)
- Kristi Beshiri
- Smruthy Sivakumar (ORCID: https://orcid.org/0000-0001-7790-5615)
- Etienne Rouleau (ORCID: https://orcid.org/0000-0002-5955-7968)
- Luc Friboulet (ORCID: https://orcid.org/0000-0002-1129-4978)
- Mohamed Amine Bani (ORCID: https://orcid.org/0000-0003-4834-4905)
- Isabelle Sourouille
- Julieta Elena Rodriguez
- Gautier Boillet
- Rastislav Bahleda (ORCID: https://orcid.org/0009-0001-8245-0544)
- Marine Valéry (ORCID: https://orcid.org/0000-0002-7787-6911)
- Peggy Dartigues
- Radwa Sharaf (ORCID: https://orcid.org/0000-0002-5214-380X)
- Massimiliano Gelli
- Filippo Gustavo Dall’Olio (ORCID: https://orcid.org/0000-0003-0903-6109)
- Alina Fuerea (ORCID: https://orcid.org/0009-0002-7074-0189)
- Mihaela D. Aldea (ORCID: https://orcid.org/0000-0001-7685-051X)
- Antoîne Italiano (ORCID: https://orcid.org/0000-0002-8540-5351)
- T. Pudlarz (ORCID: https://orcid.org/0009-0006-6591-2213)
- Alice Boilève (ORCID: https://orcid.org/0000-0003-3708-4909)
- Saumya D. Sisoudiya (ORCID: https://orcid.org/0000-0001-7276-8084)
- Simon Pernot (ORCID: https://orcid.org/0000-0003-4580-585X)
- Arnaud Bayle (ORCID: https://orcid.org/0000-0002-2150-7906)
- Damien Vasseur (ORCID: https://orcid.org/0000-0001-8787-1498)
- Meagan Montesion
- Michel Ducreux (ORCID: https://orcid.org/0000-0001-8649-7449)
- Antoine Hollebecque (ORCID: https://orcid.org/0000-0003-2869-7551)
- Victor Euzen (ORCID: https://orcid.org/0000-0001-8571-654X)
- Fabrice Barlési (ORCID: https://orcid.org/0000-0001-5793-3539)
- Christophe Massard (ORCID: https://orcid.org/0000-0001-5505-0564)
- Francesco Facchinetti
- A. Tarabay (ORCID: https://orcid.org/0000-0002-3804-3554)
- V. Boige
- Ludovic Lacroix
Institutions
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut Bergonié (FR)
- Hôpital Saint-Louis (FR)
- Foundation Medicine (United States)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s41698-025-01181-4
- Primary Topic
- Colorectal and Anal Carcinomas
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Philippe Foundation
- Servier
- Institut Servier