Couldn't this be fixed in a backwards compatible way by clearing the cache when this type of error occurs? We can do this by wrapping the offending line with a try/except, then checking to see if the cache is corrupted. If it is, then we clear the cache and try again.

try:
  if not s.rstrip(safe):
    return s
except UnicodeDecodeError:
  # Make sure the cache is okay, if not, try again.
  if any([not isinstance(s2, str) for q2, s2 in _safe_quoters.values()])
    # Cache is corrupted, clear it and try again.
     _safe_quoters = {}
    # Recursive call to try again
    return quote(s, safe)
  raise