ORCHARD PARK – When you haven’t made the playoffs for 16 years in a row, there are typically very few times during a season where you’re going to be a prohibitive favorite to win a game.

But for the suddenly resurgent Buffalo Bills, that’s the case Sunday afternoon when they play host to the struggling San Francisco 49ers at New Era Field.

The Bills have the much better roster from top to bottom, and even though the season debut of 49ers quarterback Colin Kaepernick casts a little bit of doubt on the outcome — particularly if he plays the way he once played for San Francisco — the Bills hold matchup advantages all over the field.

Here’s my breakdown of the game with Buffalo pursuing its fourth straight victory, something that hasn’t happened since 2008.

Three ...

1. Can Colin Kaepernick spark the 49ers? Blaine Gabbert is basically incompetent at quarterback, and quite frankly, it’s somewhat amazing that 49ers coach Chip Kelly waited five games to make the move to Kaepernick. Now that he has, Kaepernick has a chance to resurrect his flagging career which, at one time when he was leading the 49ers to a Super Bowl, looked so promising. Kaepernick can be a nightmare to play against because of his running ability, but Kelly’s up-tempo offense demands precision in the passing game, too, and that’s what Kaepernick’s problem has been the last couple years. The Bills play against this style quarterback every day in practice with Tyrod Taylor, so they should be fairly well-equipped to deal with the athletic Kaepernick, and if they can generate pressure without forcing Kaepernick to run, they should be able to bank on their backfield coverage and his inaccuracy to play well on defense.

2. Will this be LeSean McCoy’s redemptive performance against Chip Kelly? Last year, it seemed as if McCoy’s entire season was geared toward going back to Philadelphia and beating the Eagles and Kelly, their coach at the time who — gasp! — had the nerve to trade him to the Bills. That day did not go well as McCoy rushed for only 74 yards on 20 carries and after the Bills lost 23-20, he ran off the field refusing to shake Kelly’s hand, not to mention his former teammates’ hands. This week, McCoy indicated that he’s past all the hostility and that he’s cool with Kelly. My thought is that McCoy will never be cool with Kelly, and he wants to beat his old coach, even if he’s no longer in Philadelphia. The timing couldn’t be better for McCoy as he’s currently on a nice roll coming off a 150-yard game, the Bills are pounding the ball on the ground and are now ranked third in the league, and the 49ers’ no-name defense — especially with star linebacker NaVorro Bowman out for the year — ranks 31st against the rush, allowing 146.8 yards per game.

3. Is this the week the Bills’ passing game comes alive? San Francisco’s defense does nothing very well, so this would be an ideal day for Taylor to finally show some tangible progress. The 49ers rank 10th in the league in passing yards allowed, but that’s dubious. Teams have had success running, and they’ve also spent the vast majority of time in the lead against San Francisco and have scaled back their passing attacks. This is a defense devoid of playmakers, so Taylor should be able to make things happen, especially if tight end Charles Clay gets involved early and often. One guy to watch is new wide receiver Justin Hunter, who offensive coordinator Anthony Lynn said is starting to get comfortable with the offense and may warrant more playing time. Hunter made a nice debut last week, catching a touchdown pass on his first snap as a Bill.

and Out

Rex Ryan said he’s proud of how his team has bounced back from the egregious 0-2 start by winning three in a row. But if the Bills are going to be taken seriously as a wild-card playoff contender, they need to stretch that winning streak to five games by beating the woeful 49ers on Sunday, and then going down to Miami next week and beating the equally woeful Dolphins. After that comes a brutal stretch with games against New England, Seattle, and Cincinnati, so there cannot be a slip-up these next two weeks. First things first, Sunday. The Bills have most of the advantages working in their favor in this game against the 49ers, not the least of which that they’re back at home after a two-week roadie; there’s no excuses to lose. Their run game should eat well against a weak 49ers defense, and Buffalo’s defense ranks fifth in points allowed, fourth in sacks per pass attempt, and the Bills are plus-9 in turnover margin. Kaepernick figures to be a little rusty, and with a porous offensive line in front of him, I can’t imagine him doing all that much against the Bills’ defense, especially if the front seven led by Kyle Williams, Jerry Hughes, Lorenzo Alexander and Zach Brown continues to play the way it has. Take care of business, Buffalo. That’s what playoff teams do. I think the Bills will. MY PICK: Bills 31, 49ers 16.

By the Numbers

3 Consecutive wins by the Bills by double digits. It’s the first time in Rex Ryan’s head coaching career that this has happened.

40 Times Chip Kelly-coached teams in Philadelphia and San Francisco have scored at least 20 points, and his record in those games is 27-13.

9 The Bills rank second in the NFL in turnover differential with a plus-9, second only to Minnesota’s plus-11.

Bills (3-2) vs. 49ers (1-4)

When: 1 p.m. Sunday

Where: New Era Field, Orchard Park

TV/Radio: Fox (Channel 7, channel 31)/96.5 FM WCMF

Series record: 49ers lead 6-5

Last meeting: Buffalo lost 45-3 in 2012

Line: Bills by 9.