Other high-profile omissions include experienced wings Jonny May and Jack Nowell.
Meanwhile, Borthwick has recalled 95-cap veteran prop Dan Cole, 35, who last played for England in the 2019 Rugby World Cup final.
Northampton fly-half Fin Smith is one of five uncapped players in the squad.
London Irish wing Ollie Hassell-Collins, Gloucester hooker George McGuigan, and Harlequins pair Cadan Murley and Jack Walker are the four other new caps.