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Management of patients with squamous cell carcinoma metastasis of an unknown primary in the head and neck (SCC-HNCUP) remains a challenge. In Denmark, the diagnostic work-up and treatment of SCC-HNCUP is standardized and follow national guidelines provided by the DAHANCA group. However, international consensus regarding treatment strategy is lacking and so is knowledge about treatment outcome. The clinical radiotherapy (RT) target for SCC-HNCUP according to current DAHANCA guidelines involves bilateral regional lymph nodes and potential mucosal primary tumor sites. Neck dissection (ND) alone is recommended in N1-disease (UICC 7).

The aim of the current study is to evaluate the oncologic outcome in patients with SCC-HNCUP treated according to the Danish national guidelines. 

Prospectively registered data was extracted from the DAHANCA database. All patients treated for SCC-HNCUP at Aalborg, Aarhus and Odense University Hospitals in the period 2014-2020 were included. The median follow-up was 35 months (IQR 44 months).

A total of 177 patients were identified. 153 (86%) patients received curatively intended treatment with surgery, RT and chemotherapy, either alone or in combination. Twenty (11%) patients received palliative treatment. Four patients underwent no treatment. Sixty-one (34%) patients were treated with curatively intended RT alone, 54 (31%) received CRT with concomitant weekly cisplatin 40 mg/m². Fourteen patients received accelerated RT with 6 fractions per week (66Gy/33fx/5½ weeks) and 108 patients received conventional RT with 5 fractions per week (66 Gy/33fx/6½ weeks). Forty-six patients treated curatively with RT/CRT concurrently received nimorazole. Forty and 25 patients had a ND prior to RT and CRT, respectively. Thirty-five patients received ND as only curative modality.

Neck node p16 status was unknown in 21 patients, negative in 78 patients and positive in 78 patients. Two patients had EBV-positive neck nodes.

A primary tumor or secondary cancer emerged in the head and neck region in 17 patients during follow-up.  Three tumors emerged in the hypopharynx, three in oral cavity and 11 in the oropharynx, of which 6 involved base of tongue.  Time to loco-regional failure varied between 2 and 62 months. In three patients, a possible primary tumor emerged outside the head and neck area (1 esophagus, 2 lung).

The 3-year OS for the total population was 72.8% (95% CI: 65.1, 79.1). For patients treated with curative intend, the OS at 3-years was 81.1% (73.4, 86.8). Three-year OS in patients with p16 positive disease treated curatively was 92.2% (82.1, 96.7), while patients with p16-negative and unknown p16 status had OS of 73.0% (60.5, 82.1) and 69.3% (31.2, 89.1), respectively.

Our data support that SCC-HNCUP is comparable to other head and neck cancers in terms of prognosis. Thorough multidisciplinary work-up is important in order to plan optimal curative treatment strategies for these patients.