Head and Neck

Immune-Mediated Approaches to Head and Neck Cancer


Head and neck cancer is the eighth most common cancer in the United States3,4

HNSCC has traditionally 2 distinct etiologies with different biological and clinical characteristics. Amongst the patients tested for human papillomavirus (HPV):

Patients with HPV positive locally advanced HNSCC demonstrate significantly better prognosis.7-11

Management goals in HNSCC depend on disease stage12

Early stage or locally advanced disease

Treatment goal is cure and is typically composed of a combination of surgery, radiation therapy, and chemotherapy

Recurrent or metastatic HNSCC

Treatment of recurrent/metastatic disease depends on performance status. While enrollment in a clinical trial is the preferred option, treatment options for recurrent/metastatic HNSCC include a platinum-based combination chemotherapy regimen, single agent chemotherapy, and immunotherapy if disease progresses on or after platinum-containing chemotherapy

Outcomes for patients with recurrent or metastatic HNSCC remain poor

Median overall survival (OS) in first-line recurrent/metastatic is 10.1 months2

Currently, non-chemotherapy based regimens do not exist in the first-line recurrent/metastatic HNSCC setting. Because chemotherapy is associated with acute toxicity concerns and poor outcomes, there is a need for novel approaches to treating recurrent/metastatic HNSCC.2


Head and neck cancer has the seventh highest mutational burden among tumor types13

Several immune-based approaches are being explored18


Therapeutic vaccines

Cell-based therapy that activates cytotoxic T cells and induces the production of antibodies by introducing antigens into a patient


Adoptive cell therapy (eg, CAR-T)

Selecting and engineering T cells for high tumor specificity ex vivo, then reintroduced into the patient


Immune checkpoint inhibitors

Targets key immune checkpoints to harness the innate immune response to eliminate tumor cells

Evading immune inhibition with the immune checkpoint blockade

Because tumors may induce tolerance among tumor-specific T cells and create an immunosuppressive microenvironment, the immune checkpoint blockade may help to restore the patient’s preexisting immune response. Antitumor immune responses can be activated by blocking these immune-inhibitory pathways, including the checkpoint proteins of PD-L1 and CTLA-4.18-20

Durable response could be achieved by disrupting multiple pathways

Disrupting multiple, non-redundant immune pathways such as CTLA-4 and PD-L1 may offer synergistic antitumor effects. Complementary inhibition enhances T-cell activation, proliferation, and differentiation into memory T cells. The formation of memory T cells may promote durable antitumor response.21-23

Immunotherapy is changing the treatment landscape

In 2016, two immune checkpoint inhibitors were approved for use after platinum failure for patients with recurrent/metastatic HNSCC.

AstraZeneca is currently investigating combination immunotherapy for both first-line and second-line treatment of HNSCC. By targeting multiple checkpoint receptors, immunotherapy may provide synergistic and additive benefits for a broader patient population, with antitumor properties and improved durability of response.24,25

REVIEW our immuno-oncology clinical trials for HNSCC

CAR-T=chimeric antigen receptor T cell therapy; PD-1=programmed cell death-1; PD-L1=programmed cell death ligand-1; CTLA-4=cytotoxic T-lymphocyte–associated antigen 4.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.


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