I cannot speak for American Express for sure, where I work we sell Visa gift cards. We have received a couple complaints that our Visa gift cards cannot be used to pay for a hotel room. I am guessing it either has to do with either the lack of recourse on a prepaid card, or the certain degree of anonymity that comes with paying with a gift card. (although we will only sell to bank customers so they are not at all anonymous as to who actually bought the card, whoever is using the card may be a different story). I guess I am a little confused when you said not the card on file, but then said pay for a room. I guess you could keep a different CC on file and maybe pay the actual bill with a gift card? I doubt the hotel would go for that, but no harm in asking them. Gift cards are not as useful as an actual debit or credit card. Gift cards have certain limitations.
Long answer short, I believe it would be unlikely to use them to pay for a hotel. You can probably use them to buy tickets however (assuming they take AMEX).