Comprehensive Analysis Reveals No Significant Correlation Between p16/CDKN2A Expression and Treatment Outcomes in Laryngeal Squamous Cell Carcinoma

Helen Hieu Nguyen; Ishita Gupta; Ashley Cellini; John C Papadimitriou; Ranee Mehra; Daria A Gaykalova; Matthew E Witek

doi:10.1002/hed.28044

Comprehensive Analysis Reveals No Significant Correlation Between p16/CDKN2A Expression and Treatment Outcomes in Laryngeal Squamous Cell Carcinoma

Head Neck. 2024 Dec 23. doi: 10.1002/hed.28044. Online ahead of print.

Authors

Helen Hieu Nguyen¹, Ishita Gupta^{2

3}, Ashley Cellini⁴, John C Papadimitriou⁴, Ranee Mehra⁵, Daria A Gaykalova^{2

3

6}, Matthew E Witek^{7

8}

Affiliations

¹ University of Maryland School of Medicine, Baltimore, Maryland, USA.
² Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
³ Department of Otorhinolaryngology-Head and Neck Surgery, Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Medical Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
⁷ Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁸ Medstar Georgetown University Hospital, Washington, DC, USA.

PMID: 39714101
DOI: 10.1002/hed.28044

Abstract

Background: The p16/CDKN2A protein is being explored as an independent prognostic marker in laryngeal cancer, with studies suggesting that p16-positive patients may have a better prognosis. While its role is well-established in oropharyngeal squamous cell carcinoma (OPSCC) related to HPV, ongoing research indicates its potential prognostic value in laryngeal cancer, even in HPV-negative cases.

Methods: In this study, we investigated the association between survival outcomes and p16 expression in a cohort of 310 laryngeal cancer patients from the Cancer Genome Atlas (TCGA) Program and the University of Maryland Medical Center (UMMC).

Results: In the TCGA cohort, patients with high p16 protein expression had a significantly higher probability of disease-free survival (DFS) at 89%, compared to 51% in the low p16 protein group (p = 0.0266). Additionally, the mean relative p16 protein expression decreased significantly with advancing TNM stage, measured at 1.116 for stage II, 1.075 for stage III, and 0.6204 for stage IV (p = 0.7871 for stage II vs. stage III, p = 0.0065 for stage III vs. stage IV, p = 0.0031 for stage I vs. stage IV). Protein expression for p16 also correlated with CDKN2A retention/deletion status (p = 0.0077), where the DFS was higher in patients with retained CDKN2A than those with deleted CDKN2A (p = 0.0187). Multivariate analysis of the UMMC and TCGA cohorts revealed that both an increase in the patient's age and higher T stage significantly increased the risk of mortality (p = 0.05, p = 0.01, respectively).

Conclusion: While this study observes trends suggesting that low p16 protein expression is associated with longer DFS and advanced TNM stage in laryngeal cancer, the multivariate analysis did not establish p16 as an independent prognostic factor. These findings suggest that while p16 may have a biological role in tumor progression, its utility as a standalone prognostic marker in clinical outcomes requires further validation.

Keywords: CDKN2A; clinical outcome; laryngeal cancer; larynx; p16.

Abstract

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