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Objective <p>Head and neck squamous cell carcinoma of unknown primary (HNSCC-CUP) represents a clinical challenge due to its heterogeneity and lack of consensus in diagnostic and therapeutic management. This study analyses the impact of HPV, diagnostic and therapeutic strategies, as well as the outcomes in CUP patients in Spain.</p> Methods <p>A retrospective multicenter study (2018–2021) was conducted across eight tertiary care hospitals in Spain, including patients HNSCC-CUP undergoing different diagnostic and therapeutic strategies. Variables analysed included demographic data, clinical features, diagnostic techniques, therapeutic modalities, and clinical outcomes. Statistical analyses involved Kaplan-Meier curves, log-rank tests, and Cox regression.</p> Results <p>A total of 112 patients were identified. HPV positivity (p16 and/or HPV DNA) was observed in 30.4% of cases. The primary tumor was identified in 26.7% of cases, predominantly in the ipsilateral tonsil and tongue base and more frequently among the HPV positive cohort (61.7%). Three-year overall survival (OS) was 69.6%, with better OS observed in multimodal treatments (<i>p</i> = 0.020). Extracapsular extension and unimodal treatments were associated with worse prognosis (<i>p</i> &lt; 0.05). The identification of the micro primary tumour during the diagnostic surgery was associated with a better overall and recurrence-free survival.</p> Conclusions <p>HNSCC-CUP remains a diagnostic and therapeutic challenge. Diagnostic surgery and multimodal treatment improve OS, especially in patients with advanced disease. This study highlights the importance of molecular diagnosis and multidisciplinary management in HNSCC-CUP and underscores epidemiological differences related to HPV status. Prospective studies are needed to validate these findings.</p>

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Diagnostic work-up strategies impact on head and neck Squamous Cell Carcinoma (SCC) of unknown primary survival: a national multicentric retrospective analysis

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Carlos M. Chiesa Estomba,
  • Paulina Droppelman-Alvarez,
  • Aina Brunet,
  • David Virós-Porcuna,
  • Amaya Roldan-Fidalgo,
  • Patricia Corriols-Noval,
  • Javier Lainez Sánchez,
  • Fabian García-Velasco,
  • Jon A. Sistiaga-Suarez,
  • Carlos Pollán-Guisasola,
  • Andrea Martínez-Camerano,
  • Xavier García-Foraster,
  • Fernando López-Álvarez,
  • Aleix Rovira

摘要

Objective

Head and neck squamous cell carcinoma of unknown primary (HNSCC-CUP) represents a clinical challenge due to its heterogeneity and lack of consensus in diagnostic and therapeutic management. This study analyses the impact of HPV, diagnostic and therapeutic strategies, as well as the outcomes in CUP patients in Spain.

Methods

A retrospective multicenter study (2018–2021) was conducted across eight tertiary care hospitals in Spain, including patients HNSCC-CUP undergoing different diagnostic and therapeutic strategies. Variables analysed included demographic data, clinical features, diagnostic techniques, therapeutic modalities, and clinical outcomes. Statistical analyses involved Kaplan-Meier curves, log-rank tests, and Cox regression.

Results

A total of 112 patients were identified. HPV positivity (p16 and/or HPV DNA) was observed in 30.4% of cases. The primary tumor was identified in 26.7% of cases, predominantly in the ipsilateral tonsil and tongue base and more frequently among the HPV positive cohort (61.7%). Three-year overall survival (OS) was 69.6%, with better OS observed in multimodal treatments (p = 0.020). Extracapsular extension and unimodal treatments were associated with worse prognosis (p < 0.05). The identification of the micro primary tumour during the diagnostic surgery was associated with a better overall and recurrence-free survival.

Conclusions

HNSCC-CUP remains a diagnostic and therapeutic challenge. Diagnostic surgery and multimodal treatment improve OS, especially in patients with advanced disease. This study highlights the importance of molecular diagnosis and multidisciplinary management in HNSCC-CUP and underscores epidemiological differences related to HPV status. Prospective studies are needed to validate these findings.