Description

HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) often presents as carcinoma of unknown primary (CUP), challenging traditional diagnostic and treatment paradigms. With the increasing incidence of HPV-driven disease among younger patients with favorable prognoses, clinical priorities have shifted toward minimizing treatment burden while maintaining oncologic efficacy.

This session will focus on Denmark’s comprehensive national initiative addressing CUP in the HPV era, centered on the implementation of transoral robotic surgery (TORS) mucosectomy as a diagnostic and therapeutic tool. Recently adopted into national guidelines, TORS mucosectomy has proven effective in identifying hidden primaries and guiding tailored therapy. When combined with a structured radiation de-escalation protocol, this strategy allows for significant reduction in treatment toxicity—especially in cases where the primary tumor is definitively located and fully resected.

The session will also address the broader implications of integrating TORS into CUP work-up, including multidisciplinary coordination, patient selection, and the evolving role of surgical pathology in risk stratification. Together with Denmark’s complementary use of circulating tumor HPV-DNA (ctHPV-DNA) for post-treatment surveillance, these developments reflect a national shift toward more individualized, function-preserving management in HPV-associated head and neck cancer.

Internationally relevant, this Danish model demonstrates how evidence-based innovation, when scaled through national policy, can refine diagnostics, support de-intensified therapy, and improve patient outcomes.

Outcome Objectives

By the end of this session, participants will be able to:

- Examine the role of TORS mucosectomy in the diagnostic work-up of HPV-associated CUP.
- Explain how the Danish national guideline incorporates TORS and supports treatment de-escalation based on surgical findings.
- Compare oncologic and functional implications of TORS-guided versus empiric radiation-based approaches.
- Recognize key criteria for patient selection and multidisciplinary workflow in implementing TORS for CUP.
- Interpret how real-world adoption of TORS and de-escalated therapy can be applied in other national or institutional settings.

Background (references)

see attachment