The lowest-ranked team left in the FA Cup will take on the joint-most successful club in the competition’s history on Friday as Cambridge United host Manchester United in the humble surroundings of Abbey Stadium.

Cambridge United sit mid-table in League Two, a full 79 places in England’s pyramid below their Premier League high-flying opponents. A victory for the home side in the fourth round would be the biggest upset of this year’s thus far giant-killing-devoid competition and one of the biggest shocks in the FA Cup’s 143-year history. United boss Louis van Gaal, who has already been the victim of a sizable upset during his time in England, when his side were hammered 4-0 by League One side MK Dons in the League Cup, is determined not to be on the losing end.

“For me it’s not a change or an exception because we prepare our matches the same way as we prepared the matches in the Premier League or a friendly game,” he said at his pre-match press conference. “Of course, it’s maybe different because I have to say again what I say to you, that in our minds you believe that you are playing against a weaker opponent, but it’s not like that. It’s a different opponent with another playing style with other players and we have to beat them, because when you lose the game you are out.”

After a defeat to Southampton, Manchester United won 2-0 at Queens Park Rangers on Saturday to remain in fourth place in the Premier League. But it was a performance that further inflamed the debate about Van Gaal’s formation. Fans chanted for the Dutch coach to switch from his 3-5-2 shape to a 4-4-2 and it was with the latter formation that both goals arrived. However, while admitting that the players are still “not comfortable” with his favored setup, he called the discussion about it “ridiculous,” and hinted that he would be sticking with three at the back.

Cambridge will be looking to take advantage of any vulnerability, having come through matches against League One opponents Fleetwood Town followed by League Two sides Mansfield Town and Luton Town to reach the FA Cup fourth round for the first time in 15 years. It has been quite a 12 months for the club, nicknamed the U’s. In May, they returned the Football League -- England’s top four divisions -- after a nine-year absence thanks to triumphing in the Conference playoff final at Wembley.

It has been a long way down from the club’s glory days in the early 1990s when they came close to getting into the inaugural season of the Premier League. They also reached the FA Cup quarterfinals in 1991, the same year as their only previous meeting with Manchester United, in the League Cup. Striker Dion Dublin was a member of that team and would soon after complete a transfer to Old Trafford.

The connection between the clubs does not end there. The current Cambridge squad contains former Manchester United winger Luke Chadwick, although the 34-year-old is an injury doubt. Cambridge, now managed by Richard Money, will definitely be without cup-tied trio Jordan Chiedozie, Johnny Hunt and Matteo Lanzoni. Manchester United will be missing Chris Smalling, Jonny Evans and Ashley Young, but welcome back Luke Shaw and Robin van Persie.

Prediction: Cambridge have scored freely at home this season, including in a 4-0 win last time out, and may have some success in unsettling a still vulnerable Manchester United defense. However, there is surely little chance of a repeat of the stunning result against MK Dons, which came in the troubled early days of Van Gaal’s reign. While there remain plenty of kinks for Van Gaal to iron out, Manchester United should avoid disaster at Abbey Stadium.

Cambridge United 1-3 Manchester United

Kickoff time: 2:55 p.m. EST

TV channel: Fox Sports 1

Live stream: Fox Sports Go, Fox Soccer 2Go