Spider-man: No Way Home - Hello Nephews

The actresses who played Aunt May in all the spider-man movies also played in a roll in other films where their character was in a close relationship Dr Octopus's actor.

Additionally, in Marvel comics canon. Doc Ock did have a relationship with Aunt May and attempted to marry her. This explains the comic panel in the notes.

And as of right now, the two of them are still in good terms to even cooperate with one another.

Ultimately the joke is; if things actually worked out for Otto, he would be Peter’s step-uncle. Making Spider-man his nephew.