Despite higher stages at presentation, patients with high-risk (HR) HPV-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) have better survival rates compared to those with non-HPV-related (HPV−) disease. However, significant comorbidity and the number of patients who suffer failed treatment, recurrent disease, late metastasis, and death are increasing along with the incidence of HPV+ HNSCC. A cytotoxic T-cell-dependent immune response is required to clear these antigenic cancers. This provides a unique opportunity to employ immune modulators in therapy. Galectin-3 (Gal-3) is a lectin and glycoprotein involved in numerous immunosuppressive functions. Inhibitors are currently under clinical investigation for various diseases. Gal-3 expression was evaluated in HR-HPV+ and HPV− HNSCCs and regional lymph node metastases by tissue microarray. HR-HPV+ cases were more likely to be Gal-3-positive (Gal+) [50% (14/28)] than HPV− cases [18% (9/50), p = 0.004]. No difference in the number of Gal+ cases was identified between primary [30% (16/53)] and metastatic [28% (7/25)] cancers (p = 1); 53% (9/17) of primary HPV+ cancers were Gal+ and 45% (5/11) of metastatic HPV+ cancers were Gal+ (p = 1). Nineteen percent (7/36) of primary HPV− cancers were Gal+ and 14% (2/14) of metastatic HPV− cancers were Gal+ (p = 1). Gal-3 positivity was observed in a subset of HNSCC, suggesting a potential role for therapeutic inhibition in this tumor type. The significantly higher rates of expression seen in HR-HPV+ versus HPV− HNSCC suggest particular promise in the setting of HPV infection. The relatively consistent Gal-3 expression rates observed between metastatic and primary tumors argues against progressive Gal-3 expression in metastasis.
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Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11:9–22.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2015;66:7–30.
Marur S, Forastiere AA. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91:386–96.
Lee DW, Anderson ME, Wu S, Lee JH. Development of an adenoviral vaccine against E6 and E7 oncoproteins to prevent growth of human papillomavirus-positive cancer. Arch Otolaryngol Head Neck Surg. 2008;134:1316–23.
Gooi Z, Chan JYK, Fakhry C. The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. Laryngoscope. 2016;126:894–900.
Marur S, D’Souza G, Westra WH, Forastiere A. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781–9.
Koch WM. Clinical features of HPV-related head and neck squamous cell carcinoma: presentation and work-up. Otolaryngol Clin North Am. 2012;45:779–93.
Marklund L, Hammarstedt L. Impact of HPV in oropharyngeal cancer. J Oncol. 2011;2011:509036.
O’Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA. Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol. 2012;48:1191–201.
Ruzevick J, Olivi A, Westra WH. Metastatic squamous cell carcinoma to the brain: an unrecognized pattern of distant spread in patients with HPV-related head and neck cancer. J Neurooncol. 2013;112:449–54.
Spanos WC, Nowicki P, Lee DW, Hoover A, Hostager B, Gupta A, et al. Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009;135:1137–46.
Williams R, Lee DW, Elzey BD, Anderson ME, Hostager BS, Lee JH. Preclinical models of HPV+ and HPV− HNSCC in mice: an immune clearance of HPV+ HNSCC. Head Neck. 2009;31(7):911–8.
Krupar R, Robold K, Gaag D, Spanier G, Kreutz M, Renner K, et al. Immunologic and metabolic characteristics of HPV-negative and HPV-positive head and neck squamous cell carcinomas are strikingly different. Virchows Arch. 2014;465:299–312.
Allen CT, Clavijo PE, Van Waes C, Chen Z. Anti-tumor immunity in head and neck cancer: understanding the evidence, how tumors escape and immunotherapeutic approaches. Cancers (Basel). 2015;7:2397–414.
Farhad M, Rolig AS, Redmond WL. The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment. Oncoimmunology. 2018;7:e1434467.
Kindt N, Journe F, Ghanem GE, Saussez S. Galectins and carcinogenesis: their role in head and neck carcinomas and thyroid carcinomas. Int J Mol Sci. 2017;18:2745.
Wang LP, Chen SW, Zhuang SM, Li H, Song M. Galectin-3 accelerates the progression of oral tongue squamous cell carcinoma via a Wnt/β-catenin-dependent pathway. Pathol Oncol Res. 2013;19(3):461–74.
Weber M, Büttner-Herold M, Distel L, Ries J, Moebius P, Preidl R, et al. Galectin 3 expression in primary oral squamous cell carcinomas. BMC Cancer. 2017;17:906.
Wehrhan F, Büttner-Herold M, Distel L, Ries J, Moebius P, Preidl R, et al. Galectin 3 expression in regional lymph nodes and lymph node metastases of oral squamous cell carcinomas. BMC Cancer. 2018;18:823.
Mesquita JA, Queiroz LMG, Silveira ÉJD, Gordon-Nunez MA, Godoy GP, Nonaka CFW, et al. Association of immunoexpression of the galectins-3 and -7 with histopathological and clinical parameters in oral squamous cell carcinoma in young patients. Eur Arch Oto-Rhino-Laryngol. 2016;273:237–43.
Punt S, Thijssen VL, Vrolijk J, De Kroon CD, Gorter A, Jordanova ES. Galectin-1, -3 and -9 expression and clinical significance in squamous cervical cancer. PLoS ONE. 2015;10:e0128119.
Vuong L, Kouverianou E, Rooney CM, McHugh BJ, Howie SEM, Gregory CD, et al. An orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and augments response to PD-L1 blockade. Cancer Res Cancer Res. 2019;79:1480–92.
Coppock JD, Lee JH. mTOR, metabolism, and the immune response in HPV-positive head and neck squamous cell cancer. World J Otorhinolaryngol Neck Surg. 2016;2:76–83.
The authors would like to acknowledge and thank the University of Virginia Biorepository & Tissue Research Facility for their skill and expertise in the construction of the tissue microarray and performance of the in situ hybridization and immunohistochemical assays used in this study.
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This work was approved by the Institutional Review Board of the University of Virginia (IRB #13310).
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Coppock, J.D., Mills, A.M. & Stelow, E.B. Galectin-3 Expression in High-Risk HPV-Positive and Negative Head & Neck Squamous Cell Carcinomas and Regional Lymph Node Metastases. Head and Neck Pathol (2020). https://doi.org/10.1007/s12105-020-01195-3
- Galectin 3
- Head and neck cancer
- Oropharyngeal cancer
- Squamous cell carcinoma
- Human papilloma virus