Aside from isolation techniques, which are another subject altogether, you may find leakage effects from your 500V to other parts of the circuit as a result of the impedance of the board and impurities on the board. The best way to get around that is to encircle the high voltage area with an earthed guard band.

There are also other considerations of creepage and clearance. The voltage can arc across closely spaced tracks where the voltage is high enough. With high enough voltage, epecially in high humidity, there can also a long term effect leading to breakdown.

-Aubrey