Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma is Cost-Effective in Southern China

Population-wide screening of middle-aged adults for nasopharyngeal carcinoma (NPC) is cost-effective in southern China, where NPC is endemic. A two-step strategy first employing Epstein-Barr virus (EBV) serology, and if positive, followed by nasoendoscopy, magnetic resonance imaging (MRI) or MRI with nasopharyngeal polymerase chain reaction (PCR) for EBV are the most cost-effective strategies, according to research presented at the 2023 ASTRO annual meeting.

These conclusions are derived from a secondary analysis of the Guangdong cluster-randomized controlled trial (NCT00941538), in which nearly 360,000 residents 30 to 69 years old living in 16 cities in southern China were randomly allocated to NPC serologic screening or a control group. This study showed that over a 10-year period, EBV serologic screening may reduce NPC mortality in high-risk populations.

In the current study led by Jacob Miller, MD, Assistant Professor of Radiation Oncology at Cleveland Clinic Taussig Cancer Institute, six high-risk populations living in two provinces in southern China (Guangdong and Guangxi) were assessed based on screening costs and quality-associated life-years (QALYs) gained associated with 12 different screening strategies, each of which were contingent on the results of anti-EBV IgA serology. For each strategy and population, the investigators evaluated the incremental cost-effectiveness ratio (ICER), defined as the incremental cost per incremental quality-adjusted life-years per screened subject. A willingness to pay (WTP) threshold of 1.5 times the per-capita gross domestic product (GDP) was used to assess cost-effectiveness.

Most competitive screening strategies in these high-risk populations

“The incidence of nasopharyngeal carcinoma in southern China is the highest in the world, so it makes sense to screen for this cancer to try to detect it at an early stage,” says Dr. Miller. “We demonstrated that in these six cities, whose population is nearly the population of the United States, NPC screening is cost-effective in both men and women, and screening tended to be cost-effective from approximately age 40 until age 60, which is relevant because these are the ages of peak NPC incidence. We also observed that more cases could be detected using nasopharyngeal MRI. While MRI increases the cost of screening, it remains cost-effective.”

The result resulted in the following findings:

• Compared with endoscopy alone, use of MRI reduced NPC mortality by an additional 5 to 7%.
• A strategy of endoscopy plus annual EBV serology was cost-effective in all six populations at the WTP threshold of 1.5 ICER/GDP and in five of the six populations at an ICER/GDP WTP threshold of 1.00.
• Endoscopy plus annual serology had the lowest median ICER/GDP (0.62). Strategies that incorporated MRI in individuals deemed to be high risk following nasopharyngeal polymerase chain reaction (PCR) testing were similarly cost-effective in four to five of the six populations.
• Strategies that employed MRI approximately doubled incremental costs but remained cost-effective (ICER/GDP ≤ 1.5) in most regions due to increased sensitivity.
• Use of nasopharyngeal PCR as a triage test decreased referrals for endoscopy and MRI by 37% but decreased relative screening sensitivity by 5%. Use of nasopharyngeal PCR without MRI was dominated by other strategies.
• Introduction of MRI without nasopharyngeal PCR increased costs and decreased the number of NPC deaths relative to endoscopy plus annual serology.
• Incorporating both nasopharyngeal PCR and MRI yielded similar ICER/GDP and NPC mortality as MRI alone, but reduced MRI utilization.

“Four screening approaches were most competitive,” says Dr. Miller. The least expensive approach was EBV serology plus endoscopy. More cases at a slightly higher cost could be detected by combining serology, endoscopy and MRI. MRI utilization could be reduced while maintaining screening effectiveness by reserving its use to individuals found to have EBV DNA on a nasopharyngeal swab.

Public health perspective will drive choices

“Each strategy performs very well in these populations within the local economic constraints,” Dr. Miller says. “They have differing advantages depending upon the public health perspective. For hospitals that may not choose to use MRIs for screening purposes, serology plus endoscopy is a good alternative. If the goal is to maximize the number of lives saved, MRI could be added to maximize sensitivity. Nasopharyngeal swabs can be used to triage MRI use.”

These results are applicable only to southern China. Further research is warranted to study high-risk populations in other regions, where incidence rates, available resources and public health priorities may differ, Dr. Miller believes.