Has the papal states ever expanded on your game?
They never used to expand in the original versions of the game but since the latest patches came they seem to want to expand all the time. Typically if you attack Sicily as Byzantine then sooner or later the Pope will launch an attack on Naples. Also Florence is usually one of his targets.

If you really want to have some fun then go on crusade, get Jerusalem then sell it to the Pope. It's like waking a sleeping beast. He will easily conquer the holy land and Egypt and probably press on to destroy everything else if given time.