What’s New in Squamous Cell Carcinoma

Posted on: October 9th, 2026 by Our Team

Squamous cell carcinoma, or SCC, is the second most common type of skin cancer. More people are being diagnosed with it every year.

Here is the good news: almost all SCCs are cured with one simple procedure in the office. And here is even better news. For the small number of tumors that act more aggressively, the past few years have brought some real breakthroughs. Doctors now have a gene test that predicts which tumors are dangerous, a blood test that can spot cancer coming back before a scan can, and a medicine that can shrink advanced tumors before surgery.

Here is what’s new in squamous cell carcinoma, and what it means for you.

1. Testing the Genes Inside Your Tumor

For many years, dermatologists judged how risky an SCC was by looking at a few things: how big it was, how deep it went, where it was on the body, and how the cells looked under a microscope. These staging systems work fairly well. But they have a weakness. They label a lot of tumors as “high risk” even though most of those tumors never spread.

What the test does. A test called the 40-gene expression profile (brand name DecisionDx-SCC) measures how active 40 different genes are inside your tumor. It uses the tissue that was already removed during your biopsy or surgery, so you do not need another procedure.

The results put your tumor into one of three groups:

• Class 1 — low risk. About 91% of these patients have no spread of cancer after 3 years.
• Class 2A — higher risk. About 81% have no spread after 3 years.
• Class 2B — highest risk. About 44% have no spread after 3 years.

Why this matters. The test is most useful when it moves a patient into a lower risk group. In one study of 300 patients whose tumors were called “high risk” by the usual rules, more than half turned out to be low risk based on their genes. Those patients could reasonably have fewer scans and shorter follow-up. Only about 8% were found to need the most aggressive treatment plan.

What’s new. Researchers are now asking a harder question: who actually benefits from radiation after surgery? In a study of 920 patients, only the Class 2B group clearly did better with radiation added. Class 1 and Class 2A patients did not seem to benefit. If future studies confirm this, it could spare many people weeks of treatment they do not need, while making sure the patients who do need radiation get it.

A newer 14-gene test has also been reported, with promising results for predicting spread and survival. This field is growing quickly.

An honest caveat. Not every expert is convinced. A 2025 review raised concerns about how the original study data were collected and how the accuracy numbers were reported. The major national cancer guidelines have not yet added gene testing to their official treatment plans. At Peak Skin Center, we treat this test as one helpful piece of information — not a replacement for careful staging and clinical judgment.

2. A Blood Test That Watches for Cancer’s Return

One of the most exciting new areas in skin cancer is the ability to look for cancer with a simple blood draw.

How it works. Tumors constantly shed tiny pieces of their DNA into the bloodstream. These pieces are called circulating tumor DNA, or ctDNA. Each tumor’s DNA has its own unique pattern, almost like a fingerprint. A lab can study your tumor, build a test designed just for you, and then search your blood for those exact DNA pieces — even in extremely small amounts.

Where it fits into care. Doctors describe three main uses:

• Before treatment — to get a sense of how much cancer is present and how it may behave.
• Right after treatment — to look for tiny amounts of cancer left behind that no scan can see.
• During follow-up — to catch cancer returning earlier than an exam or a CT or PET scan would, and to cut down on false alarms from imaging.

What the research shows. Most of the strongest evidence so far comes from similar cancers elsewhere in the body. In head and neck squamous cell carcinoma, patients who still had ctDNA in their blood after treatment relapsed much sooner. In some cases, the blood test signaled the cancer’s return before imaging did. In anal squamous cell carcinoma, patients with ctDNA in their blood after treatment had a much higher risk of the cancer coming back.

Something specific to skin cancer. Skin cancers caused by sun exposure carry a distinctive pattern of DNA damage from ultraviolet light. A 2025 study of more than 73,000 blood samples showed that this “UV signature” can be found in the blood very reliably. This can help confirm that a cancer actually started in the skin, even when its origin is unclear.

Where things stand today. ctDNA testing for SCC is still considered an emerging tool. It is not yet part of standard national follow-up guidelines. Those guidelines still recommend regular skin and lymph node exams — usually every 3 to 6 months for the first two years in high-risk patients — with imaging added when needed. For our highest-risk patients, we are happy to discuss ctDNA testing as an added tool.

3. Immunotherapy Before Surgery

This may be the single biggest change in the care of advanced SCC.

The problem it solves. Some SCCs grow large, often on the scalp, face, ear, or nose. Surgery may still be possible, but it could mean removing an eyelid, an ear, part of the nose, or damaging facial nerves. In the past, patients faced a difficult choice between major disfiguring surgery and treatment that was not strong enough.

The breakthrough. Cemiplimab is a type of immunotherapy. It works by releasing the brakes on your immune system so it can attack the cancer. In an important study of 79 patients with stage II to IV SCC, four doses were given before surgery. The results:

• In 51% of patients, no living cancer cells were found in the tissue removed at surgery.
• In another 13%, only a tiny amount of tumor remained (10% or less).
• 68% had their tumor shrink on imaging.

With longer follow-up, 85% of patients were alive and free of major problems at 24 months. Just as important, not one patient whose tumor completely disappeared had the cancer come back.

Guidelines now include it. National guidelines list cemiplimab before surgery as an option to consider for very-high-risk SCC when the tumor is:

• Growing quickly
• Spreading along the skin between the tumor and nearby lymph nodes
• Right on the edge of being removable
• Likely to need surgery that would not cure the cancer, or that would cause serious loss of function

Can surgery sometimes be skipped? Possibly. A 2026 study followed 51 patients with advanced but removable head and neck SCC who were treated with cemiplimab alone, without surgery. After two years, 90% were still alive without dying from their cancer, and 82% had no worsening of disease. A separate study from the United Kingdom of 25 patients found that 64% responded, including 11 whose tumors disappeared completely. In that group, 85% avoided surgery altogether, and surgery remained a safe backup option for those whose cancer grew. These studies were small, but they suggest that some patients — especially older adults who are not good candidates for surgery — may be able to keep an eye, an ear, or a nose.

Immunotherapy after surgery, too. A large 2025 trial called C-POST tested cemiplimab after surgery and radiation in 415 patients with very high-risk features. It lowered the risk of the cancer returning or of death by 68%. After two years, 87% of patients on cemiplimab were still cancer-free, compared with 64% on placebo. This is now a strongly recommended option in national guidelines for eligible patients. Importantly, a similar trial using a different immunotherapy drug, pembrolizumab, did not show the same benefit. These medicines should not be assumed to work the same way.

Safety matters. Immunotherapy is usually easier to tolerate than chemotherapy, but it does carry risks. In the C-POST trial, about 24% of patients on cemiplimab had a serious side effect, compared with 14% on placebo. About 1 in 10 stopped treatment because of side effects. Because these drugs turn up the immune system, they can cause inflammation in the thyroid, lungs, liver, intestines, or skin. Patients who have had an organ transplant or who have an autoimmune disease need especially careful evaluation, since immunotherapy can cause the body to reject a transplanted organ.

What This Means for You

Most squamous cell carcinomas are still handled the same way they always have been. They are found early, removed completely — often with Mohs surgery — and followed with routine skin checks. Nothing above changes that for most patients.

But if your SCC is large, has come back, grows deep, involves nerves, is on the head or neck, or occurs after a transplant or with a weakened immune system, the picture has genuinely changed:

• Gene testing can clarify your true risk.
• Blood testing may catch problems sooner.
• Immunotherapy may shrink a tumor enough to save an eye, an ear, or a nose — or clear it completely.

Prevention still works best. Daily broad-spectrum sunscreen, sun-protective clothing, staying out of tanning beds, and regular full-body skin exams remain the most powerful tools we have. If you have had several skin cancers, an organ transplant, or a melanoma in the past five years, you should be seen regularly by a dermatologist.

Schedule your skin cancer screening at Peak Skin Center. Catching a skin cancer early is often the difference between a 20-minute office visit and a long, complicated treatment plan.