In the current environment, there is nothing that cannot be duplicated. It's a question of the cost of making something difficult to duplicate or the cost of duplicating something that has been made harder to copy. So, whether you use screen-printed letterheads or computer-generated imaging on your letters, it can be very easily scanned and copied. Today, even ID size/passport size photos are being xeroxed (photocopied) instead of taking a fresh photo print. The only thing "most" common scanners can't copy is watermarks. But that also is being factored into the latest scanners.
What Are You Trying to Solve?
So the question that arises is this: What do you want it for? And what are you scared of happening? Remember also that an outsider will not know what safety features you put in your letterhead and therefore won't know whether the letterhead is fake or real. So again, what are you trying to solve? The answer depends on that.