Shell + Perl solution:

#!/bin/sh
INFILE=test.in
# get number of lines not matching "^#" (-v inverses the results)
non_comment_lines=$(cat $INFILE | grep -cv "^#"); 
if [ 0 -lt $non_comment_lines ]; then
  perl ./process_file.pl < $INFILE
fi
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For a Perl-only solution, slurp in the file contents and use a regex:

#!/usr/bin/env perl
use strict;
use warnings;
$/=undef;
open my $fh, "<", "test.in";
my $file = <$fh>;
if ($file =~ m/^#/) {
  print "process me!\n";
}
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