NPC: Plasma EBV DNA cannot replace nasoendoscopy and biopsy during COVID-19 pandemic

Plasma Epstein-Barr virus (EBV) measurement, even when supplemented by imaging, cannot replace nasoendoscopy and biopsy in nasopharyngeal cancer (NPC) management during the COVID-19 pandemic, according to consensus recommendations by an international multidisciplinary group of experts.

A total of 33 NPC experts from the fields of otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology from China, Hong Kong, Taiwan, Thailand, Malaysia, Singapore, Indonesia, Italy, France, Belgium, Spain, the US, Canada, and Tunisia were involved in development of the consensus recommendations. [Lancet Oncol 2022;doi:10.1016/S1470-2045(22)00505-8]

The experts, representing 51 international and national oncological and surgical societies, completed a modified Delphi consensus process involving three rounds of an online survey in August 2021. The survey focused on the use of plasma EBV DNA in NPC screening and diagnosis, staging, treatment response monitoring, post-treatment surveillance, and diagnosis of recurrent disease in a normal non-pandemic setting as well as in the context of the COVID-19 pandemic with severe personnel and resource constraints and risk of COVID-19 transmission during the aerosol-generating nasoendoscopy procedure or biopsy.

A majority (97 percent) of the experts disagreed with the use of plasma EBV DNA without histological confirmation for NPC diagnosis. There was also strong disagreement about the use and repeated use (ie, 4 weeks after an initial undetectable titre) of plasma EBV DNA, either exclusively (88 percent disagreement) or in combination with EBV immunoglobulin A (IgA) antiviral capsid antigen (94 percent disagreement), to replace nasoendoscopy and other diagnostic or imaging tools for NPC screening and diagnosis during the COVID-19 pandemic.

Unanimous disagreement was noted about the use of plasma EBV DNA and IgA antiviral capsid antigen, without imaging, to replace nasoendoscopy and biopsy as the only NPC staging investigations during the COVID-19 pandemic. Most experts (73 percent) disagreed with using plasma EBV DNA and imaging to replace nasoendoscopy and biopsy for NPC staging.

Seventy-three percent of experts disagreed with measuring plasma EBV DNA alone, without clinical consultations, for monitoring of response to radical treatment, or for treatment response monitoring in recurrent or metastatic disease without the use of imaging or other diagnostic tools. A majority (91 percent) also disagreed with the use of plasma EBV DNA alone, without imaging, nasoendoscopy or biopsy, for confirmation of local and regional remission following radical treatment.

Seventy percent of experts agreed that during the pandemic, plasma EBV DNA and imaging can replace nasoendoscopy and biopsy as the only relapse surveillance tools after completion of radical treatment. However, 82 percent disagreed with the use of plasma EBV DNA alone for this purpose.

All experts disagreed with the use of plasma EBV DNA alone, without imaging, nasoendoscopy and biopsy, for diagnosis of clinically suspicious NPC recurrence during the pandemic. Most experts (79 percent) also disagreed with replacement of nasoendoscopy and biopsy with plasma EBV DNA and imaging for diagnosis of NPC recurrence.

Similarly, 94 percent of experts disagreed with the use of increased or progressively rising plasma EBV DNA titres alone, without histological and imaging correlation, as the only criterion to diagnose NPC recurrence during the pandemic.

“Plasma EBV DNA in combination with imaging can be considered an acceptable alternative in a very restricted clinical setting, but cannot replace face-to-face consultations and nasoendoscopy, and cannot be used alone (without imaging) for NPC management,” the researchers noted.

“We hope that these recommendations can further stimulate international harmonization and more affordable use of plasma EBV DNA in low- and middle-income countries, and foster future research in more sensitive and accurate tumour markers for NPC and other cancers,” said Dr Victor Lee of the Department of Clinical Oncology, University of Hong Kong, who led the research.