A Korean research team, led by Professor Kim Na-young at the Department of Internal Medicine of Seoul National University Bundang Hospital (SNUBH), analyzed the differences between males and females with stomach cancer positive for the Epstein-Barr virus (EBV), which infects more than 90 percent of the population.

EBV, a herpes virus transmitted through saliva, is the most common virus in the world and is well known as the cause of infectious mononucleosis, also known as the "kissing disease."

There is no specific prevention for EBV, but if you do get infected, it usually passes without any symptoms, and it's so common that antibodies have been found in more than 90 percent of the population, often overlooked. However, EBV is a class 1 carcinogen according to the World Health Organization (WHO), and is responsible for a variety of cancers, including stomach and nasopharyngeal cancers.

In the case of gastric cancer in particular, about 10 percent of all gastric cancers are classified as EBV-positive, and the medical community has recently published the presence or absence of this virus as one of the four criteria for identifying the molecular characteristics of gastric cancer cells.

The research team set out to characterize EBV-positive gastric cancers and to determine how they differ by sex. The study used data from 4,587 patients diagnosed and treated for gastric cancer at SNUBH between 2003 and 2023.

The analysis showed that 13.3 percent of male gastric cancer patients had EBV gastric cancer, compared to only 3.3 percent of females, and that the total number of patients was about 10 times higher in males because gastric cancer itself is more common in males. In addition, EBV gastric cancer was characterized by a lower degree of differentiation compared to typical gastric cancer.

While lower differentiation is typically associated with a poor prognosis, with deeper infiltration and indistinguishable tissue morphology leading to classification as diffuse (cancer that spreads below the mucosa), EBV gastric cancer was thought to have an overall survival rate higher than that of normal gastric cancer.

However, the latest SNUBH study showed that this is only true for males. In males, the five-year survival rate for EBV gastric cancer was significantly higher at 90.8 percent compared to 85.3 percent for other gastric cancers, but in females, the rates were virtually unchanged at 88.5 percent and 87 percent with and without EBV, respectively.

The researchers speculated that these results may be related to sex differences in the immune system against EBV gastric cancer: females have an overall higher immune function due to sex hormones such as estrogen, which results in a lower incidence of EBV-positive gastric cancer but does not affect survival when it does occur, while males have a higher incidence of EBV-positive gastric cancer, but are less likely to metastasize, resulting in improved survival.

"This study details the differences in the presentation of Epstein-Barr virus gastric cancer between males and females," said Professor Kim, "This study provides evidence that endoscopic treatment may be the preferred option for poorly metastatic male EBV-positive early gastric cancer, even when poorly differentiated submucosal invasion is suspected, instead of risky gastrectomy."

The findings were recently published in the international journal, Gastric Cancer.