If you have head and neck cancer, your pathology report may include a line that includes a detail such as “PD-L1 CPS: 15.” It’s easy to skim past, but this number can play a primary role in which treatment your care team recommends first, especially if your cancer has come back or spread.
Let’s explore what PD-L1 is, how your CPS score is calculated, and how it shapes your treatment options.
What is PD-L1?
Your immune system has built-in “brakes” that stop it from attacking healthy cells. One of these brakes is a pair of proteins: PD-1, found on immune cells, and PD-L1, which can appear on other cells.
Some cancer cells make a lot of PD-L1. When PD-L1 connects with PD-1, it’s like pressing the brake, and the immune system backs off. This helps the cancer hide and keep growing.
Immunotherapy drugs called checkpoint inhibitors, such as pembrolizumab (Keytruda), block this connection. That releases the brake so your immune system can recognize and attack the cancer. Testing for PD-L1 helps predict who is more likely to benefit.
What is a CPS score?
CPS stands for Combined Positive Score. To get it, a pathologist stains a sample of your tumor and counts the cells that show PD-L1. That count includes both cancer cells and nearby immune cells. The total is divided by the number of cancer cells and multiplied by 100.
A few things that can be confusing:
- CPS is a score, not a percentage. A CPS of 30 doesn’t mean 30% of your tumor is positive. Because immune cells are counted too, the math works differently.
- Head and neck cancer uses CPS. You may hear about a different score, TPS, for other cancers like lung cancer. TPS counts only cancer cells.
- PD-L1 is common in head and neck cancer. In the main trial that set today’s standard, 85% of patients had a CPS of 1 or higher, and 43% had a CPS of 20 or higher.
What the cut-offs mean
Doctors usually group CPS results into three ranges. Here’s how they generally line up with first-line treatment for recurrent or metastatic head and neck cancer:
CPS result | What it means | What it can mean for first-line treatment* |
Less than 1 | Little or no PD-L1 detected | Pembrolizumab alone is not approved. Pembrolizumab plus chemotherapy is still an option, as is chemotherapy with cetuximab. |
1 to 19 | PD-L1 is present | Pembrolizumab alone or pembrolizumab plus chemotherapy may be options. |
20 or higher | High PD-L1 | Same options as above; in the main trial, this group saw the biggest survival benefit from pembrolizumab alone. |
*Your care team will consider your full health picture, not just this number.
Why CPS shapes first-line treatment
CPS matters most for people whose cancer has come back (recurrent) or spread (metastatic) and can’t be cured with surgery or radiation. For this group, the first treatment you receive is called first-line treatment.
In 2019, the FDA approved pembrolizumab for first-line treatment of recurrent or metastatic head and neck cancer, based on a large trial called KEYNOTE-048. The trial compared pembrolizumab to the previous standard, chemotherapy plus cetuximab. The approval allows pembrolizumab to be used:
- On its own, if your CPS is 1 or higher. In the trial, pembrolizumab alone helped people live longer than the older standard in this group.
- Together with chemotherapy (platinum and 5-FU), regardless of your CPS.
The higher the CPS, the stronger the benefit tended to be. For people with a CPS of 20 or higher, median survival with pembrolizumab alone was about 14.9 months, compared with 10.7 months with the older standard.
Immunotherapy alone or with chemo? Pembrolizumab alone usually has fewer side effects than chemotherapy. Adding chemotherapy may shrink the cancer faster, which can matter if you have a lot of symptoms. Your CPS, how quickly the cancer is growing, and your overall health all factor into this choice.
If your CPS is less than 1, pembrolizumab alone isn’t an approved option. But that doesn’t mean immunotherapy is off the table: pembrolizumab with chemotherapy is approved regardless of PD-L1 level. Researchers note that better tools are still needed to guide treatment for people with low PD-L1.
CPS now matters earlier, too
CPS isn’t only for advanced cancer anymore. In June 2025, the FDA approved pembrolizumab for some people with newly diagnosed, locally advanced head and neck cancer that can be removed with surgery, if their CPS is 1 or higher.
In this approach, pembrolizumab is given before surgery, then continued with radiation (with or without chemotherapy) afterward. In the KEYNOTE-689 trial, it lowered the risk of the cancer coming back, getting worse, or causing death. It was the first checkpoint inhibitor approved in this curative setting.
That means PD-L1 testing may now happen right at diagnosis, before surgery is planned. If you’re facing surgery for stage III or IVA head and neck cancer, it’s worth asking whether your tumor has been tested.
Things to keep in mind about your score
- It’s one piece of the puzzle. Some people with low CPS respond to immunotherapy, and some with high CPS don’t.
- Results can vary. Different tests and different tissue samples can give different scores. The FDA-approved test for pembrolizumab in head and neck cancer is called PD-L1 IHC 22C3 pharmDx.
- Your score can change over time. If your cancer comes back, your doctor may consider retesting a newer sample.
- New options are being studied. Clinical trials are testing new drugs for head and neck cancer, such as amivantamab, which received FDA Breakthrough Therapy designation in 2026 for HPV-unrelated advanced disease.
Questions to ask your care team
- Has my tumor been tested for PD-L1? What is my CPS?
- Which test was used, and on which tissue sample?
- Based on my CPS, what first-line options do I have?
- Should I get immunotherapy alone or with chemotherapy? Why?
- What side effects should I watch for with immunotherapy?
- If my cancer comes back, should my tumor be retested?
- Are there clinical trials I might qualify for?
Disclaimer: The information provided in this article is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Outcomes4Me is not acting as your caregiver, and any suggestions or guidance offered should not replace the advice of your healthcare provider or qualified medical professional. Always seek the guidance of your physician or other qualified health provider with any questions you may have regarding a medical condition.
