Polyomavirus Antibodies for Merkel Cell Carcinoma Recurrence Detection

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare skin cancer that is often caused by a virus called the Merkel cell polyomavirus. In fact, about 80% of MCC cases in the United States are linked to the virus. About half of MCC patients make special proteins that are specific to this virus, called antibodies. Tracking how their antibody levels rise and fall can help doctors understand whether their cancer has responded to treatment, or when it is coming back (recurring).

This was a 12-year study of more than 500 patients who received an antibody blood test, called the AMERK test. When antibody levels stayed low or kept falling, there was a 99% chance the cancer would not return in the next few months. But just a single positive test meant that there was a 36% chance the cancer would recur within 3 months and a 68% chance within 2 years. 90% of recurrences happened within 14 months of a first positive blood test. Over half of the time, this test helped find recurrences sooner than could be seen on scans.

This means that tracking AMERK trends could help doctors catch MCC earlier and reduce unnecessary scans for patients who are doing well. If you have MCC and produce these antibodies, regularly doing these blood tests could give your doctors an early warning sign of recurrence and help guide follow-up care.

For more information see the “Serology for Merkel Cell Carcinoma” page on merkelcell.org.

Abstract

Importance: Merkel cell carcinoma (MCC) is typically caused by the Merkel cell polyomavirus (MCPyV) and recurs in 40% of patients. Half of patients with MCC produce antibodies to MCPyV oncoproteins, the titers of which rise with disease recurrence and fall after successful treatment.

Objective: To assess the utility of MCPyV oncoprotein antibodies for early detection of first recurrence of MCC in a real-world clinical setting.

Design, setting, and participants: This prospective cohort study used a data and specimen repository from 2008 to 2020 in Seattle, Washington. Patients with MCC with locoregional disease underwent serum antibody testing at diagnosis. Statistical analysis was conducted between 2020 and 2025.

Main outcomes and measures: The first posttreatment titer was necessary to establish a trend and was not used to assess risk (deferred). Subsequent titers were defined as (1) falling or negative, (2) rising, or (3) stable compared with the preceding titer.

Results: Among the 503 patients in the cohort (median [IQR] age at diagnosis, 70 [62-77] years; 40% female), 1402 tests were performed; 247 (49%) were seropositive. A total of 877 were falling or negative, 62 were rising, 317 were stable, and 146 were deferred. Median (IQR) follow-up was 4.2 (1.8-7.4) years. On average, antibody titers fell by half every 3 months among patients not experiencing a recurrence. After a falling or negative titer, the likelihood that a given patient would remain recurrence-free for 3 months was 99.3% (95% CI, 98.6%-99.8%). In contrast, after a single rising titer, the risk of recurrence over the next 3 months was 36% (95% CI, 22%-52%), increasing to 58% (95% CI, 40%-78%) by 12 months and 68% (95% CI, 48%-86%) by 24 months. A rising titer preceded clinical or radiographic evidence of recurrence in 57% of cases (20/35). The median (IQR) interval between a rising titer and clinical disease detection was 3.7 (1.1-7.5) months, with 90% of recurrences (18/20) occurring within 14 months of the rising titer. Recurrences and antibody titers were analyzed in 196 patients with multiple blood draws.

Conclusions and relevance: In this prospective cohort study, given a negative predictive value of 99.3%, a falling or negative titer may obviate the need for imaging, reducing radiation and contrast dye exposure. Conversely, a rising antibody titer should trigger closer follow-up, as it may lead to earlier detection of clinical recurrence and initiation of therapy.