Merkel cell polyomavirus (MCPyV) status

What is measured: whether a Merkel cell carcinoma carries integrated Merkel cell polyomavirus, and the patient's antibody response to its oncoproteins. How: immunohistochemistry for the viral large T antigen (CM2B4 antibody) or PCR for viral DNA on the tumour; serum antibodies to the small and large T oncoproteins (the AMERK test) in about half of patients at diagnosis, whose titre falls after successful treatment and rises months before a recurrence is visible (antibodies to the capsid protein are common in healthy people and useless). Virus-negative tumours carry an ultraviolet mutational signature, very high tumour mutational burden and TP53 and RB1 mutations; virus-positive tumours have few mutations yet respond just as well to PD-1 and PD-L1 blockade (avelumab in JAVELIN Merkel 200, pembrolizumab in KEYNOTE-017, retifanlimab). What a result changes: prognosis (virus-positive slightly better), the surveillance strategy (serial titres in seropositive patients in place of some imaging), stratification in trials, and eligibility for T-cell therapies directed at viral antigens. Where it matters: Merkel cell carcinoma.