Nasopharyngeal carcinoma: Significance of changes in epstein‐barr virus‐related antibody patterns following therapy

Abstract

Sera were collected a t intervals of 3 t o 8 months over a 4-t o 5-year period from more than 103 patients with nasopharyngeal carcinomas (NPC) and examined for their spectra and titers of antibodies t o Epstein-Barr virus (EBV)-related antigens. They were titrated for IgG, IgA and I g M antibodies t o EB viral capsid antigen (VCA), for IgG and IgA antibodies t o the D (diffuse) and R (restricted) components of the EBV-determined early antigen (EA) complex, and for antibodies t o the EBVassociated nuclear antigen (EBNA). In the as yet untreated patients the incidences and titers of most of the antibodies increased with the stage of the disease; i.e., essentially with the total tumor burden. Such increases were observed in individual patients whose disease ultimately progressed t o death, a t times well i n advance of the recognition of relapses o r metastases. Increases were not noted o r were only minor and delayed i n some fatal cases if the tumor extended t o the cranial cavity in the absence of significant involvement of cervical lymph nodes. I n contrast, patients who responded well t o therapy and remained clinically free of disease during the 4-o r 5-year observation period after, a t most, early minor relapses, showed gradual, steady declines in the titers of all antibodies except anti-EBNA. Thus, VCA-specific IgA and D-specific IgA and IgG became undetectable in t i m e in many of the patients. I n several long-term survivors the declines were arrested a t given levels o r a reversal t o increasing titers was noted which was followed i n time by detection of a recurrent tumor o r metastases in some cases, but not in others who remain under close observation. It would appear that serologic monitoring of NPC patients may warn of recurrent tumor activity well before it becomes clinically evident.

Independent Effect of EBV and Cigarette Smoking on Nasopharyngeal Carcinoma: A 20-Year Follow-Up Study on 9,622 Males without Family History in Taiwan

“…In several prognosis studies, the anti-EBVs declined significantly after nasopharyngeal carcinoma treatment and elevated again when nasopharyngeal carcinoma relapsed (5)(6)(7)(8). In our previous report from this cohort study, the hazard ratios associated seropositivity of anti -EBV viral capsid antigen immunoglobulin A and anti -EBV DNase were higher for the nasopharyngeal carcinoma developed <5 years than that developed z5 years after recruitment (13).…”

“…Malignancies linked to EBV infection include nasopharyngeal carcinoma, and a variety of methods have been used to detect antibodies against EBV antigens (anti-EBV) in patients with the disease (2,4). Numerous studies have shown diagnostic and prognostic utility of anti-EBV for nasopharyngeal carcinoma (5)(6)(7)(8). Anti-EBVs are found frequently in sera from nasopharyngeal carcinoma patients, and they may be used as a diagnostic tool (9)(10)(11)(12).…”

Epstein--Barr Virus Gene Expression in Nasopharyngeal Carcinoma

“…The high titres of IgA antibodies to EA and VCA which are associated with NPC (Henle & Henle, 1976;Zeng, 1985) and the fact that such titres tend to reflect tumour load (Henle et al, 1977) would imply that the tumour itself is the source of these lytic cycle antigens. Indeed some NPC biopsies appear to express transcripts usually associated with entry of cells into the productive cycle Tugwood et al, 1987) and the passage of NPC cells in nude mice in some cases leads to full virus replication in a small proportion of the cells (Trumper et al, 1977).…”

Frequency and levels of antibodies to Epstein-Barr virus-specific DNase are elevated in patients with nasopharyngeal carcinoma.

“…A 0.1-unit sample of DNase from crude homogenates of EBV-superinfected Raji cells in a total volume of 5Ml was incubated with 5 ,Ml of serum at room temperature for 20 min. The activity of EBV DNase was then determined as described (17).…”