Head and neck cancer includes tumors of the oral cavity, throat, larynx, nasal passages, and, increasingly, HPV-associated cancers of the oropharynx. For decades, treatment relied on combinations of surgery, radiation therapy, and chemotherapy. While these approaches remain essential, they can be difficult for patients to tolerate, and not all cancers respond well. Over the past ten years, immunotherapy—treatments that activate the body’s own immune system to fight cancer—has transformed care for many solid tumors. One of the most important advances has been the introduction of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Understanding the immunotherapy success rate for head and neck cancer can be challenging because these treatments work differently from chemotherapy, and their benefits often appear gradually rather than immediately. This patient-friendly article explains how immunotherapy works, who benefits the most, what clinical trials show about response and survival, and what real-world outcomes look like for people living with advanced head and neck cancer.
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How Immunotherapy Works in Head and Neck Cancer
The most commonly used immunotherapy drugs for head and neck cancer are PD-1 inhibitors, specifically pembrolizumab and nivolumab. These medications block the PD-1 protein on immune cells, preventing cancer cells from using this pathway to hide from the immune system. Once PD-1 is blocked, T-cells can recognize and attack the tumor more effectively. Immunotherapy does not kill cancer directly; instead, it removes barriers that prevent the immune system from defending the body.
Not all patients respond the same way. Some experience rapid and lasting shrinkage of tumors, while others have stable disease or little change. Researchers now know that certain biological features—including PD-L1 expression, HPV status, and the immune environment of the tumor—help determine the likelihood of response.
What Do Clinical Trials Show About Success Rates?
Clinical trials provide the most reliable numbers on how well immunotherapy works. The two most important studies are KEYNOTE-048, which evaluated pembrolizumab as first-line treatment, and CheckMate 141, which studied nivolumab in patients whose cancer had worsened after chemotherapy.
In the KEYNOTE-048 trial, pembrolizumab alone showed an overall response rate of about 17%, but results were significantly better—up to 23%—in patients whose tumors had high PD-L1 expression (CPS ≥20). When pembrolizumab was combined with chemotherapy, the response rate increased to 36%, making it a strong option for patients needing faster tumor shrinkage (Burtness et al., 2019). Importantly, pembrolizumab improved overall survival, especially in patients with high PD-L1 expression, and some responses lasted years rather than months.
The CheckMate 141 trial tested nivolumab in people with recurrent or metastatic head and neck cancer who had already received chemotherapy. The overall response rate was about 13%, which may seem modest, but what mattered most was durability. Many responses lasted more than a year, and overall survival improved compared with standard chemotherapy (Ferris et al., 2016). This durability is a hallmark of immunotherapy: even when response rates are not high, the benefits for responders can be life-changing.
Across studies, the success rate of immunotherapy—defined as significant and lasting tumor shrinkage—ranges from about 15% to 36%, depending on the patient’s tumor type, treatment history, and PD-L1 level. While this percentage is not as high as in some cancers like melanoma, the quality of responses and long-term survival improvements are meaningful.
Success Rates by Patient Subgroup
The likelihood of benefiting from immunotherapy differs across groups of head and neck cancer patients.
HPV-Positive (p16-positive) Oropharyngeal Cancer:
- Patients with HPV-related tumors tend to have better immune recognition and often respond more favorably to immunotherapy. Although response rates vary, these patients typically experience better overall survival in immunotherapy trials (Cohen et al., 2019).
High PD-L1 Expression:
- PD-L1 is a protein on tumor cells and immune cells. Tumors with high PD-L1 levels are more likely to respond to pembrolizumab. In KEYNOTE-048, the highest success rates were among PD-L1 CPS ≥20 patients, with significant improvements in both response and survival.
Recurrent or Metastatic Disease:
- Patients whose cancer has returned or spread to distant organs often have limited treatment options. In this group, immunotherapy provides the best chance for long-term disease control, even if initial response rates are modest.
Patients Previously Treated With Chemotherapy:
- Immunotherapy remains effective even after chemotherapy has failed, as demonstrated in CheckMate 141. Some patients who had exhausted all standard treatments lived significantly longer because of nivolumab.
Why Success Is Not Only About Tumor Shrinkage
Immunotherapy behaves differently from chemotherapy. With chemotherapy, doctors look for rapid tumor shrinkage to determine whether treatment is working. Immunotherapy can produce a slower but more durable effect. Some patients even experience “pseudoprogression,” where tumors appear larger at first due to immune cell infiltration before shrinking.
For this reason, success is often measured in terms of:
- Overall survival improvement
- Duration of response
- Quality of life
In both major trials, patients receiving immunotherapy experienced longer-lasting responses than with standard treatments, even when response rates were relatively low.
How Long Can Immunotherapy Keep Cancer Controlled?
For responders, immunotherapy can control head and neck cancer for many months or even years. In some cases, patients remain stable for long periods after stopping the medication. The durability of response is one of the strongest arguments for using immunotherapy in eligible patients.
In KEYNOTE-048, nearly 60% of responders were still in response at the two-year mark. In CheckMate 141, some nivolumab responders continued benefiting beyond the three-year follow-up period.
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Side Effects: What Patients Should Expect
Immunotherapy is generally better tolerated than chemotherapy, but it can still cause side effects. Most are mild—fatigue, skin rash, diarrhea, or low-grade inflammation. However, because immunotherapy activates the immune system, it can sometimes cause the immune system to attack healthy organs, leading to thyroid inflammation, colitis, hepatitis, or lung inflammation.
These effects are usually manageable when detected early, and patients are monitored closely during treatment. Prompt reporting of symptoms is essential.
What Patients Should Discuss With Their Oncologist
Every patient’s cancer is unique, and several factors influence whether immunotherapy is the right choice:
- PD-L1 expression level (CPS score)
- HPV status
- Whether cancer has returned after prior treatment
- How quickly tumor shrinkage is needed
- Overall health and ability to tolerate possible side effects
Patients should ask their oncology team about the benefits and risks, expected success rate for their specific cancer, and whether immunotherapy is available alone or in combination with chemotherapy.
Key Takeaway for Patients
Immunotherapy is not a cure for most people with head and neck cancer, but it has fundamentally changed treatment expectations. When discussing the immunotherapy success rate in head and neck cancer, it is important to understand that only a portion of patients experience significant tumor shrinkage; however, those who do often achieve long and meaningful survival benefits that were not possible with older treatments. For the right patient, immunotherapy can offer hope, extended life, and improved quality of life.
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Written by Armen Gevorgyan, MD