# Interactions between hematological biomarkers of virus infection and immune cells in mediating distant metastasis in nasopharyngeal carcinoma: insights into prognosis and induction chemotherapy administration

## TL;DR

This study explores how HBsAg positivity interacts with immune markers and virus load to worsen metastasis risk in nasopharyngeal cancer patients, suggesting tailored treatment approaches.

## Contribution

The study identifies novel interactions between HBsAg, EBV DNA load, and immune cell counts that mediate metastasis risk and treatment outcomes in HBsAg-positive nasopharyngeal carcinoma patients.

## Key findings

- HBsAg positivity combined with low lymphocyte count or high EBV DNA load independently predicts poor distant metastasis-free survival.
- Tumor staging effects on metastasis are mediated by these interactions, requiring tailored treatment strategies beyond induction chemotherapy.

## Abstract

Considering the increased metastatic risk in hepatitis B surface antigen (HBsAg)-positive patients with nasopharyngeal carcinoma (NPC), we aimed to investigate the interactions among HBsAg, tumor burden indicators, and immune function in the accurate stratification of prognosis and treatment for this specific cohort.

We retrospectively analysed 1650 pathologically-confirmed patients with NPC from two centers and performed interaction and mediation analyses among HBsAg, plasma Epstein-Barr virus (EBV) DNA load, and absolute lymphocyte count (ALC), concerning distant metastasis. A 1:1 random matched-paired analysis was performed to evaluate survival according to risk and treatment stratification. Treatment-related adverse events were also compared.

Overall, 17.3% (285/1650) of patients tested positive for HBsAg. Significant interactions occurred between HBsAg and low ALC (≤ 1.9×109/L) (HL), as well as between HBsAg and high plasma EBV DNA load (> 4000 copies/mL) (HE), both independently predicting poor distant metastasis-free survival (DMFS). The influence of T and N staging on tumor metastasis was mediated by HL (+) and HE (+), respectively. Among patients with stage III–IVa NPC, interaction associations presented with a worse 5-year DMFS and higher rates of severe neutropenia and leukopenia among those treated with additional induction chemotherapy (IC) than among those treated with radiochemotherapy alone.

Interactions exist between HBsAg positivity and high EBV/low ALC, mediating the effects of tumor staging and distant metastasis. The collective influence of viral infection, tumor burden, and reduced immune cells leads to worse DMFS in patients with HBsAg-positive NPC, requiring a tailored treatment beyond IC.