For patients with p16+ SCC of a cervical lymph node subsequently found to have an oropharyngeal mass on imaging, is it necessary to biopsy the primary site prior to proceeding with definitive RT?

No. When it gallops like a horse, there's no need to think of a zebra - unless you're in wild Africa.

And if the patient had presented with biopsy-proven p16+ neck node metastatic SqCC with "unknown primary" while a PET/CT showed suspicious uptake at the oropharynx, one should treat the presumed pri...

No, it is not necessary. Yes, we do it.

NCCN Guidelines Version 2.2019 Cancer of the Oropharynx

"Base of Tongue/Tonsil, etc. WORKUP" page 19 footnote "g".

"Prior to treatment, EUA with biopsy confirmation of the oropharyngeal primary site is recommended for patients presenting with a p16+ cervical l...

If one clearly sees a tumor in the oropharynx and there is already biopsy-proof of malignancy, it is reasonable and preferable to avoid an operative biopsy. It spares the patient anesthesia, pain, and most importantly, time to initiate treatment. On the other hand, a more subtle question is whether ...

If your oropharynx mass is a lateralized tonsil and you are considering unilateral RT, I would biopsy the primary. A false positive tonsil PET and with a hidden BOT primary is common.