Time Dependency for Human Papillomavirus Circulating Tumor DNA Detection after Chemoradiation as a Prognostic Biomarker for Localized Anal Cancer

Authors

Van K Morris
Weihong Xiao
Kangyu Lin
Chi Wut Wong
Michael T Wotman
Emma B Holliday
Ryan W Huey
Sonal S Noticewala
Ethan B Ludmir
Alisha H Bent
Kaysia Ludford
Craig Messick
Eugene J Koay
Grace Smith
Tsuyoshi Konishi
Brian Bednarski
George J Chang
Albert C Koong
Y Nancy You
Prajnan Das
Maura L Gillison

Publication Date

6-13-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-24-2575

PMID

39873618

PMCID

PMC12163595

PubMedCentral® Posted Date

6-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Purpose: Although detection of ctDNA weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Experimental design: Patients with stages I to III anal cancer treated with chemoradiation between December 2020 and March 2024 were evaluated for human papillomavirus (HPV) ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay, targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was estimated via Kaplan-Meier and compared using a log-rank test.

Results: Detection of HPV ctDNA at ≥3 months after chemoradiation was associated with recurrence (80% vs. 2%; OR, 168; 95% confidence interval (CI), 13.6-2,080; P < 0.0001) and inferior RFS [4.9 months vs. not reached; HR, 39.2; 95% CI, 4.6-330; P < 0.0001] relative to HPV ctDNA-negative status. Sensitivity and specificity for recurrence according to HPV ctDNA detection were 89% and 95%, respectively, with positive and negative predictive values of 80% and 98%, respectively. Differences in RFS according to HPV ctDNA status were not observed at the end of treatment (median RFS, not reached for both; HR, 1.6; 95% CI, 0.35-7.4; P = 0.48).

Conclusions: With a novel, highly sensitive assay, detection of HPV ctDNA at least 3 months after chemoradiation was associated with unfavorable survival. Future clinical trials should incorporate this 3-month post-treatment time point to identify patients with HPV-positive anal cancer at elevated recurrence risk according to HPV ctDNA status. See related commentary by Bercz et al., p. 2261.

Keywords

Humans, Anus Neoplasms, Circulating Tumor DNA, Male, Female, Middle Aged, Biomarkers, Tumor, Chemoradiotherapy, Prognosis, Papillomavirus Infections, Aged, Papillomaviridae, Neoplasm Recurrence, Local, DNA, Viral, Adult, Time Factors, Human Papillomavirus Viruses

Published Open-Access

yes

Recommended Citation

Morris, Van K; Xiao, Weihong; Lin, Kangyu; et al., "Time Dependency for Human Papillomavirus Circulating Tumor DNA Detection after Chemoradiation as a Prognostic Biomarker for Localized Anal Cancer" (2025). Faculty, Staff and Student Publications. 4440.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4440