The application window consists of the main content, which is unique for every page/screen of the website/application and surrounding parts which typically repeat unchanged on all pages or screens.
The main content is always marked by the first level heading. Thus screen reader users can always get back to the beginning of the main content using the shortcut for this heading. There is no other first level heading on the page.
The cursor is always moved to the beginning of the main content after the page is loaded. So this is the starting point of navigation. The user will get to the main content of the current page by moving the cursor forward or to the controls such as menus or top bar by moving backward.
Apart from using headings to distinguish different parts of the page, some areas are also marked by so called ARIA landmarks, so modern assistive technologies will also allow navigation by these landmarks more comfortably.