Heat oven to 400°F. Cook penne with tablespoon salt to 2 minutes short of package time; drain.
Meanwhile, heat oil in skillet; cook mushrooms 7 to 8 minutes until water evaporates. Transfer to bowl; melt butter in skillet and whisk flour 1 minute.
Gradually whisk in milk and cream; gently simmer 3 minutes. Remove from heat; add Parmesan, oregano, sauce salt, and pepper.
Fold pasta and mushrooms into sauce; transfer to deep 9-by-13-inch dish. Evenly top with mozzarella and pepperoni; foil-cover.
Bake 20 minutes, then uncovered 8 to 10 minutes until center 165°F, cheese melted, and pepperoni edges curled. Rest 5 minutes.