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Peer-reviewedCC BY 4.0Frontiers in Oncology

Postoperative ctDNA could potentially spare patients from unnecessary adjuvant therapy in HPV-negative head and neck squamous cell carcinoma: a meta-analysis

5 affiliations
  1. 1Department of Basic Medical Science, Majmaah University
  2. 2Facultad de Medicina, Universidad Mayor de San Andres
  3. 3Department of General Surgery, The Rotherham National Health Service (NHS), Rotherham General Hospital
  4. 4Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University
  5. 5Department of Precision Medicine, University of Campania “Luigi Vanvitelli”

Abstract

Background: The prognostic utility of circulating tumor DNA (ctDNA) for minimal residual disease detection in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains incompletely characterized. This meta-analysis evaluates the association between post-operative ctDNA and recurrence-free survival (RFS) in this population.

Methods: A systematic search of major databases through May 2026 identified studies evaluating post-operative ctDNA and RFS in HPV-negative HNSCC. Pooled hazard ratios (HRs) were calculated using a random-effects model.

Results: Eight studies (n=325) were included. Detectable post-operative ctDNA was associated with diminished RFS (HR = 10.07, 95% CI: 5.64–17.99) and overall survival (HR = 8.98, 95% CI: 2.93–27.58). However, sensitivity analyses substantially attenuated the pooled RFS estimate (HR range: 2.22–2.43), suggesting the primary effect magnitude may lack stability.

Conclusions: While preliminary evidence suggests an association between post-operative ctDNA and recurrence risk in HPV-negative HNSCC, these findings require cautious interpretation. The current literature is constrained by small sample sizes, heterogeneous detection methodologies, mixed-cohort inclusion, and potential confounding biases. Consequently, post-operative ctDNA remains an investigational biomarker in this setting. Clinical implementation necessitates further validation through large, prospective, multi-institutional studies employing standardized methodologies in strictly defined HPV-negative #146;populations.

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BibTeX
@article{asad2026postoperative,
  title = {{Postoperative ctDNA could potentially spare patients from unnecessary adjuvant therapy in HPV-negative head and neck squamous cell carcinoma: a meta-analysis}},
  author = {Mohammad Rehan Asad and Alejandra Flores Pusarico and Nidhi Reji and Tareq Nayef AlRamadneh and Atta Ullah Khan},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1902328},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1902328/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Postoperative ctDNA could potentially spare patients from unnecessary adjuvant therapy in HPV-negative head and neck squamous cell carcinoma: a meta-analysis
AU  - Mohammad Rehan Asad
AU  - Alejandra Flores Pusarico
AU  - Nidhi Reji
AU  - Tareq Nayef AlRamadneh
AU  - Atta Ullah Khan
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1902328
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1902328/full
AB  - Background: The prognostic utility of circulating tumor DNA (ctDNA) for minimal residual disease detection in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains incompletely characterized. This meta-analysis evaluates the association between post-operative ctDNA and recurrence-free survival (RFS) in this population.  Methods: A systematic search of major databases through May 2026 identified studies evaluating post-operative ctDNA and RFS in HPV-negative HNSCC. Pooled hazard ratios (HRs) were calculated using a random-effects model.  Results: Eight studies (n=325) were included. Detectable post-operative ctDNA was associated with diminished RFS (HR = 10.07, 95% CI: 5.64–17.99) and overall survival (HR = 8.98, 95% CI: 2.93–27.58). However, sensitivity analyses substantially attenuated the pooled RFS estimate (HR range: 2.22–2.43), suggesting the primary effect magnitude may lack stability.  Conclusions: While preliminary evidence suggests an association between post-operative ctDNA and recurrence risk in HPV-negative HNSCC, these findings require cautious interpretation. The current literature is constrained by small sample sizes, heterogeneous detection methodologies, mixed-cohort inclusion, and potential confounding biases. Consequently, post-operative ctDNA remains an investigational biomarker in this setting. Clinical implementation necessitates further validation through large, prospective, multi-institutional studies employing standardized methodologies in strictly defined HPV-negative #146;populations.
SN  - 2234-943X
ER  -