Indian Journal of Pathology and Microbiology

: 2018  |  Volume : 61  |  Issue : 3  |  Page : 311--312

HER2 as a prospective novel biomarker in squamous cell carcinomas of the head and neck

Antonio DAntonio1, Alessandro Caputo2,  
1 Department of Pathology and Cytopathology, University Hospital “S. Giovanni di Dio e Ruggi D'Aragona”, Salerno, Italy
2 Department of Medicine and Surgery, University of Salerno, Salerno, Italy

Correspondence Address:
Antonio DAntonio
Department of Pathology and Cytopathology, University Hospital “S. Giovanni di Dio e Ruggi D'Aragona”, Salerno

How to cite this article:
DAntonio A, Caputo A. HER2 as a prospective novel biomarker in squamous cell carcinomas of the head and neck.Indian J Pathol Microbiol 2018;61:311-312

How to cite this URL:
DAntonio A, Caputo A. HER2 as a prospective novel biomarker in squamous cell carcinomas of the head and neck. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Oct 26 ];61:311-312
Available from:

Full Text

Head-and-neck squamous cell carcinomas (HNSCC) represent the seventh most common cancer by incidence (686,000/year, worldwide) and ninth by mortality (375,000/year).[1] Despite advances in prevention, diagnosis, and therapy, the 5-year survival rate of patients affected by HNSCC is only 40%–60%, a number that has remained disturbingly stable for the past few decades.[2]

Together with efforts aimed at early diagnosis, the identification of a molecular marker able to pave the way for a novel therapeutic approach can be an effective way toward reducing the high mortality of HNSCC. HER2 may represent such a marker, and its role as a biomarker in HNSCC is being studied,[3] with one related study being published in this issue.[4]

Although data regarding the association between HER2 expression and the tumor-node-metastasis (TNM) stage is not conclusive, it is still possible that HER2 expression might be useful clinically. For example, it may identify a different subtype of HNSCC which may have its own therapeutic options, molecular pathogenesis, or prognosis.

For example, in some studies, HER2 has been shown to correlate with other clinicopathological parameters, such as disease-free survival.[5],[6] This may represent a different biologic behavior displayed by HNSCC's with HER2 overexpression. Such different biologic behavior is supported by other observations, for example, that HER2-positive clones tend to be selected – and sometimes enriched – in metastases.[7]

As for therapeutic implications, it has been observed that HER2 positivity may play a role in chemo-radioresistance of HNSCC.[4] If confirmed by further studies, such finding may make HER2 an important and clinically relevant prognostic marker independent from the TNM stage and histological grade.

Different therapies may be employed in HER2-positive HNSCC, the most obvious of which – HER2 inhibitors – is currently being studied in clinical trials. However, even if HER2-positive HNSCC's were not responsive to HER2-inhibitor therapy, identifying them may still shed light on the molecular pathogenesis of a subtype of HNSCC and thus possibly lead to a different therapy, more effective or safer than the current regimens.

For example, some studies have proposed a role for HER2 overactivation in the mechanism behind resistance to cetuximab treatment.[8] In parallel, some evidence suggests that HER2 inhibitors may be synergistic with EGFR-targeted therapy in treating HNSCC, possibly by overcoming such resistance.[9]

Another important point raised in the article in this issue is the possibility that subdividing HNSCC by location may provide more significant results.[4] Aggregating all squamous cell carcinomas of the head and neck into the HNSCC group may not render justice to some peculiar subtypes which may have independent molecular pathogenesis, response to therapies and prognosis.

In conclusion, efforts aimed at reducing the mortality of HNSCC are direly needed. A novel biomarker such as HER2 may represent the fruit of such efforts, and more studies aimed at clarifying its role as a biomarker in HNSCC are awaited.


1Thompson LD, Brennan P, Pinto LF. Head and neck cancers. In: Stewart BW, Wild CP, editors. World Cancer Report 2014. Lyon: IARC Press; 2014. p. 422-30.
2Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
3Pollock NI, Grandis JR. HER2 as a therapeutic target in head and neck squamous cell carcinoma. Clin Cancer Res 2015;21:526-33.
4HER2-neu expression in head and neck squamous cell cancers and its clinicopathological correlation: Results from an Indian Cancer Center. Indian J Pathol Microbiol 2018.
5Cavalot A, Martone T, Roggero N, Brondino G, Pagano M, Cortesina G, et al. Prognostic impact of HER-2/neu expression on squamous head and neck carcinomas. Head Neck 2007;29:655-64.
6Tse GM, Yu KH, Chan AW, King AD, Chen GG, Wong KT, et al. HER2 expression predicts improved survival in patients with cervical node-positive head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2009;141:467-73.
7Wei Q, Sheng L, Shui Y, Hu Q, Nordgren H, Carlsson J, et al. EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases. Ann Surg Oncol 2008;15:1193-201.
8Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med 2011;3:99ra86.
9Wheeler DL, Huang S, Kruser TJ, Nechrebecki MM, Armstrong EA, Benavente S, et al. Mechanisms of acquired resistance to cetuximab: Role of HER (ErbB) family members. Oncogene 2008;27:3944-56.