Padovani replaces Angelo Esposito on the wing and will want to continue his good form after coming off the bench to score a second-half try in the last Saturday’s defeat to Scotland.
Michele Campagnaro shifts back into his preferred centre position, as Zebre’s Tommaso Castello drops out of the matchday 23.
Another Zebre player drops out of matchday squad as Andrea Lovotti has withdrawn with illness, meaning loosehead prop Quaglio replaces him.
O’Shea has again named a heavily PRO14-dominated team, with 12 of the starting line-up playing for either Benetton or Zebre.
The replacements bench is a Benetton full-house, with all eight players plying their trade at the Conference B high-flyers.
The iconic Sergio Parisse captains his nation once again at No.8, as Benetton pair Sebastian Negri and Abraham Steyn remain at his side.
Zebre’s Guglielmo Palazzani remains at scrum-half, with Benetton’s Tommaso Allan at fly-half.
Edoardo Gori and Marco Barbini come onto bench for the Azzurri.
Italy team to face Wales in the 2019 Guinness Six Nations:
15 Jayden Hayward (Benetton Rugby)
14 Edoardo Padovani (Zebre Rugby)
13 Michele Campagnaro (Wasps)
12 Luca Morisi (Benetton Rugby)
11 Angelo Esposito (Benetton Rugby)
10 Tommaso Allan (Benetton Rugby)
9 Guglielmo Palazzani (Zebre Rugby)
1 Nicola Quaglio (Benetton Rugby)
2 Leonardo Ghiraldini (Toulouse)
3 Simone Ferrari (Benetton Rugby)
4 David Sisi (Zebre Rugby)
5 Dean Budd (Benetton Rugby)
6 Sebastian Negri (Benetton Rugby)
7 Abraham Jurgens Steyn (Benetton Rugby)
8 Sergio Parisse (c) (Stade Francais)
16 Luca Bigi (Benetton Rugby)
17 Cherif Traore (Benetton Rugby)
18 Tiziano Pasquali (Benetton Rugby)
19 Federico Ruzza (Benetton Rugby)
20 Marco Barbini (Benetton Rugby)
21 Edoardo Gori (Benetton Rugby)