Abstract
Background: Following chemo-radiotherapy (CRT) for human papilloma virus positive (HPV+) anal squamous cell carcinoma (ASCC), detection of residual/recurrent disease is challenging. Patients frequently undergo unnecessary repeated biopsies for abnormal MRI/clinical findings. In a pilot study we assessed the role of circulating HPV-DNA in identifying “true” residual disease.Methods: We prospectively collected plasma samples at baseline (n = 21) and 12 weeks post-CRT (n = 17). Circulating HPV-DNA (cHPV DNA) was measured using a novel next generation sequencing (NGS) assay, panHPV-detect, comprising of two primer pools covering distinct regions of eight high-risk HPV genomes (16, 18, 31, 33, 35, 45, 52, and 58) to detect circulating HPV-DNA (cHPV DNA). cHPV-DNA levels post-CRT were correlated to disease response.Results: In pre-CRT samples, panHPV-detect demonstrated 100% sensitivity and specificity for HPV associated ASCC. PanHPV-detect was able to demonstrate cHPV-DNA in 100% (9/9) patients with T1/T2N0 cancers. cHPV-DNA was detectable 12 weeks post CRT in just 2/17 patients, both of whom relapsed. 1/16 patients who had a clinical complete response (CR) at 3 months post-CRT but relapsed at 9 months and 1/1 patient with a partial response (PR). PanHPV-detect demonstrated 100% sensitivity and specificity in predicting response to CRT.Conclusion: We demonstrate that panHPV-detect, an NSG assay is a highly sensitive and specific test for the identification of cHPV-DNA in plasma at diagnosis. cHPV-DNA post-treatment may predict clinical response to CRT.
Highlights
Radical chemoradiotherapy (CRT) is a standard of care for patients with locally advanced anal squamous cell carcinoma (LA-ASCC) [1]
We developed an ultra-sensitive human papilloma virus (HPV) DNA generation sequencing (NGS) assay, panHPV-detect, with the ability to comprehensively detect circulating DNA of high-risk HPV genomes (16, 18, 31, 33, 35, 45, 52, and 58) and assess its relationship with disease status and response
Tumor tissue (ASCC diagnosis) and baseline blood samples were available for 21 patients (Table 2)
Summary
Radical chemoradiotherapy (CRT) is a standard of care for patients with locally advanced anal squamous cell carcinoma (LA-ASCC) [1]. The majority of patients with loco-regional disease will be cured, but patients with residual or recurrent disease may be salvaged with radical surgery making on going assessment of disease imperative. Following CRT there is no standard recommended single modality for response assessment. LA-ASCC are slow to regress and 26 weeks is said to be the optimal time-point for response assessment based on data from ACT II study [2]. Positive predictive value of these modalities is sub-optimal and can lead to unnecessary biopsies in some patients. Following chemo-radiotherapy (CRT) for human papilloma virus positive (HPV+) anal squamous cell carcinoma (ASCC), detection of residual/recurrent disease is challenging. In a pilot study we assessed the role of circulating HPV-DNA in identifying “true” residual disease
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