So in order to make use of GUILE_SITE and GUILE_SITE_CCACHE, I think we need Autoconf macros in guile.m4 that allow to specify the prefix (as in the Python example on the cited page).
-- Marc
P.S.: There is one more issue with guile.m4: When it finds the program guile-2.2, it only searches for guild-2.2, but not for guild. However, at least on Ubuntu systems, there is only guild, but no guild-2.2.
P.P.S.: Of course, in the long run we need integration of Guile in Autoconf like Python and Elisp are already integrated.