KEY POINTS
- This retrospective institutional series included 126 patients with cervical-node squamous carcinoma of unknown primary treated with curative-intent radiotherapy from 2009–2023: 97 were p16-positive and 29 p16-negative. Median follow-up was 38 months, with some patients followed for more than 15 years.
- Treatment volumes were explicitly driven by p16 status. p16-positive patients received mucosal RT limited to the ipsilateral oropharynx and nasopharynx, together with bilateral elective neck treatment; p16-negative patients received more comprehensive ipsilateral nasopharynx, oropharynx, hypopharynx and larynx coverage.
- Gross nodal disease received 70 Gy in 33 fractions, while elective mucosal and nodal volumes received approximately 50.4 Gy/28 fractions to 59.4 Gy/33 fractions. All patients were treated using IMRT, initially helical tomotherapy and later VMAT; 55% received concurrent systemic therapy.
- Five-year overall survival was 90.0% in p16-positive versus 69.2% in p16-negative disease; two-year survival was 96.7% versus 80.7%. On multivariable modeling, p16 status remained independently associated with overall survival (P=.0054).
- Only four primary mucosal tumors emerged after treatment - two in each p16 group - while five neck recurrences occurred. Crucially, every mucosal emergence and every neck recurrence occurred inside the irradiated fields, with no geographic failures attributable to the reduced mucosal strategy.
- Five-year primary mucosal control was 87.3% in p16-positive versus 65.1% in p16-negative patients, and neck control was 87.8% versus 62.1%. p16-negative disease carried greater univariate risk of mucosal emergence, HR 3.42, and neck recurrence, HR 2.68.
- Acute grade 3 toxicity included 12% dysphagia, 16% mucositis and 9% dermatitis across the cohort; nasogastric feeding was required in 16% and hospitalization in 15%. Late grade ≥2 toxicity was uncommon: grade 2 xerostomia occurred in 6%, grade 2 dysphagia in 1%, gastrostomy in 2%, and mucosal radionecrosis in 2%. Toxicity was descriptively similar between p16 groups, although missing data were counted as no toxicity.
CLINICAL TAKEAWAY
For carefully investigated p16-positive head and neck carcinoma of unknown primary, limiting mucosal irradiation to the ipsilateral naso-oropharyngeal region appears feasible without an obvious geographic-failure penalty. The absence of out-of-field mucosal or neck failures is particularly reassuring, but the evidence remains retrospective and does not establish equivalence to comprehensive mucosal irradiation in a randomized comparison.