The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus

Abstract

Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.

A Machine-Learning-Based Bibliometric Analysis of the Scientific Literature on Anal Cancer

“…Biomarkers and patient-reported outcomes also emerged as recent trend topics in ASCC. The HPV/p16 status, tumor-infiltrating lymphocytes (TILs) rate, Epidermal Growth Factor Receptor (EGFR) overexpression, circulating HPV-DNA and blood biomarkers [Neutrophil-to-lymphocyte ratio (NLR), Systemic Index of Inflammation (SII), absolute number of leukocytes and neutrophils, hemoglobin level] were the most frequently studied biomarkers [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Intensified Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Anus—A Population-Based Experience from the Danish Anal Cancer Group

“…Further intensification of the local treatment (to lower the risk of local failures) should also be considered in future studies, by exploring new radiotherapy techniques and concomitant systemic options like immunotherapy [25,26]. Nevertheless, there is an urgent need for tools to improve the selection of patients who will benefit from ICT prior to CRT [27,28].…”

Construction and validation of a prognostic nomogram for anal squamous cell carcinoma

“… 2 , 9 , 10 , 11 , 12 Researchers have reported that some hematological and immunohistochemical indicators may play a prognostic role in patients with ASCC who received definitive treatment. 13 , 14 , 15 Casadei‐Gardini et al enrolled 308 ASCC patients to develop a logistic nomogram using the pre‐treatment systemic inflammation index (platelet × neutrophil/lymphocyte), pre‐treatment nodal status and pre‐treatment hemoglobin levels in order to predict the prognosis of patients treated with concurrent chemoradiation. 16 However, for patients newly diagnosed with ASCC, there is a lack of effective prognostic models to better predict individual patient survival outcomes.…”