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The Dutch defender emerged as the first defender to score two goals in a English top-flight match for Spurs since the Belgian defender in March 2013.
Match summary
Micky Van de Ven nods into the net twice in first half
The home side's Jake O'Brien has equalizer disallowed after VAR review
Pape Matar Sarr scores final goal in 89th minute
The defeat is Everton's first at Hill Dickinson Stadium
Micky van de Ven scored on two occasions as Tottenham extended their winning streak on the road in the Premier League and delivered Everton their initial loss at Hill Dickinson Stadium.
Everton were unbeaten in their last five matches at their new ground at Bramley-Moore Dock, having left Goodison Park behind after more than a century at the end of the previous campaign.
But Spurs captain Van de Ven struck on two occasions from corners in the first half to place their strong form at risk, and they were failed to turn it around before Pape Matar Sarr - assisted by ex-Everton forward Richarlison - headed home a third to put the game to bed.
Jake O'Brien believed he had levelled the tally five minutes after the defender's first goal, directing a powerful header past Guglielmo Vicario from an set-piece.
The Portuguese striker, meanwhile, failed to convert a number of chances, while the Italian goalkeeper made a series of fine saves to guarantee Tottenham went five away games unbeaten in the English top flight.
But the video assistant referee stepped in, advising Craig Pawson to review the goal on the screen and the official ruled that the winger and the attacker were in an illegal position and had impeded with the Spurs keeper.
This victory elevates Thomas Frank's side up to third in the Premier League, a handful of points off north London rivals and leaders Arsenal.
The Merseyside club remain 14th and are half a dozen points clear of the relegation zone.
After a uninspiring midweek display in the European competition against the French side, where they mustered a only attempts on target, the manager opted for the French striker in attack instead of former Toffees player the Brazilian.
The summer signing was failed to make much of an impact before being substituted for Richarlison after 60 minutes on the pitch, but it emerged he proved unnecessary in the final outcome.
Defender Van de Ven transformed into an offensive threat to be reckoned with.
Spurs' first goal came from a well-worked set-piece play, with Rodrigo Bentancur directing the ball back across the face of goal for an unmarked Van de Ven to head home.
And the captain - filling in as captain in Cristian Romero's unavailability - notched his second in first-half stoppage time as he rose above the England keeper to nod in.
The Dutchman was equally impressive in defence, partnering effectively with Kevin Danso as the duo dealt excellently with the numerous deliveries thrown their way by the opposition.
The club's recent stadium had been a fortress, but it appears the novelty may have worn off somewhat and fans flocked to the exits after Sarr's third for Tottenham.
The end in the team's unbeaten home run won't be a major worry for David Moyes, but their striker situation will be.
Beto and Thierno Barry - the Everton's pair of recognised strikers - had scored just a single goal between them before the weekend's match.
And they were unable to add to that miserable tally on a wet and gloomy evening on in Liverpool.
The striker's form was summed up when he opted to overhead kick a clear chance from close range, despite having room and opportunity to readjust for a simpler attempt that would have challenged the keeper.
Barry, too, was unable to make an impact after replacing the starter in the 65th minute.
It wasn't for a shortage of opportunity. Most of the home side's attacks came through the winger and the forward, who tirelessly whipped dangerous balls into the Tottenham penalty area.
Everton: Moyes' men travel to the Stadium of Light in the Premier League on Monday, 3 November at 20:00 GMT.
Tottenham: Spurs go to Newcastle's ground on late October for their next round Carabao Cup tie against the Magpies.
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