862P - Clinical utility of circulating tumor HPV16 DNA detection in plasma from oropharyngeal squamous cell carcinoma patients

Background

Human papillomavirus-driven (HPV) oropharyngeal cancers (OPC) are treated with aggressive multimodality regimens, despite their usually favourable prognosis. Yet, ∼25% of cases will develop recurrent or distant metastasis. Clinical monitoring of tumour progression and treatment response is often insufficient to detect asymptomatic lesions, delaying salvage treatment and reducing chances of cure. Therefore, we are exploring the clinical utility of measuring circulating tumour HPV DNA (ctHPVDNA) in HPV-driven OPC patients to guide outcome stratification and improve disease monitoring.

Methods

ctHPV16DNA levels were measured in plasma samples from OPC patients and controls from South America and Europe using droplet digital PCR (ddPCR). HPV16E6 serology results and well-annotated lifestyle and clinical information were available, and findings were tested for associations between ctHPV16DNA status/levels and patient clinical information. All samples were part of the HEADSpAcE study, coordinated by the International Agency for Research on Cancer (IARC). Funding: INCa_16295 and EUH2020_825771.

Results

Baseline plasma samples from HPV-seropositive (n=75) and seronegative (n=26) OPC cases, and 57 HPV-seronegative controls (n=57) were tested, and we reached 100% specificity and an overall sensitivity of 92.0% (69/75) in detecting ctHPV16DNA in HPV16-seropositive cases. 10/11 patients with small volume disease (cT1/T2 N0) were positive for ctHPVctDNA, and increasing levels were observed according to N (p=0.01) and clinical stage (p=0.0029). Moreover, baseline detection of ctHPV16DNA was associated with a reduced risk of death (HR= 0.38; p=0.034) and disease relapse (HR= 0.2; p=0.028).

Conclusions

We showed a high accuracy of plasma ctHPVDNA detection by ddPCR in a case series of OPC from Europe and South America. ctHPV16DNA levels/status in baseline plasma were associated with disease volume, and a reduced risk of relapse and death, suggesting its use in patient outcome stratification. Next, we will test ctHPVDNA in post-treatment plasma samples as a potential tool for improving patient management through a more efficient monitoring of minimal residual disease during patient surveillance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ana Carolina de Carvalho, International Agency for Research on Cancer.

Funding

Institut National Du Cancer (INCa, France) - European Union - Horizon 2020.

Disclosure

All authors have declared no conflicts of interest.