\version "2.22.1"

  %Setting staff size before the paper block, everything is okay
  
  %#(set-global-staff-size 16)
  
\paper {
  #(define fonts
    (set-global-fonts 
     #:roman "Cambria"
     #:factor (/ staff-height pt 20)
   ))
}

%Setting staff size after the paper block, the font setting reverts.

#(set-global-staff-size 16)

\header {
  title = "HEADER" }

\relative c' { c4 c c c 
c4 c c c
c4 c c c
c4 c c c
c4 c c c
c4 c c c
c4 c c c}