If you flash a Sense 2.22 based custom ROM, its recommended that you flash the updated firmware package (S-off required) or else wait until the 2.22 based OTA rolls out for your version (which will include "official" firmware).
If the updated firmware is not installed, 2.22 based ROMs will usually cause some major bugs, like excessive long boot time, broken WiFi and Bluetooth, etc.
S-off is usually not "required" to flash a ROM per se. This is an exception where the older firmware modules (not included in the ROM itself) are not playing well with the newer based ROMs.
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Phone: AT&T HTC One (M8)
Tablet: Samsung Galaxy Tab Pro 8.4 (WiFi only)