By Lynne Eldridge, MD 

Updated on July 21, 2023

 Medically reviewed by Doru Paul, MD

Squamous cell carcinoma (SCC) in the lung is one form of non-small cell lung cancer. Non-small cell lung cancers account for about 85% of lung cancers, many of them associated with smoking. Of these, roughly 30% are squamous cell carcinomas.¹

Squamous cell carcinoma begins in the tissues that line the air passages in the lungs. It is also known as epidermoid carcinoma. Most squamous cell carcinomas of the lungs are located centrally, usually in the larger bronchi that join the trachea to the lung.

This article discusses squamous cell carcinoma in the lungs and its symptoms and causes. It also presents information about diagnosis and treatment.

Illustration by Julie Bang for Verywell Health

What Are Squamous Cell Subtypes?

Squamous cell lung cancers can be divided into subtypes based on how they look under a microscope and how they behave. These squamous cell subtypes were newly defined by the World Health Organization in 2015. They are called:²

• Nonkeratinizing (lacking the keratin protein in the cells studies)

• Keratinizing (any amount of keratin in the tumor)

• Basaloid (specific features of more than 50%, whether keratin is present or not)

Survival rates vary significantly between the subtypes, with basaloid squamous cell carcinoma having a better survival rate than the others, according to research study results.² The subtypes are also important in terms of how cancer responds to a specific type of drug treatment.

What Are the Stages of Squamous Cell Carcinoma?

Squamous cell carcinoma of the lungs is broken down into four stages:³

• Stage 1: The cancer is localized and has not spread to any lymph nodes.

• Stage 2: The cancer has spread to lymph nodes or the lining of the lungs, or is in a certain area of the main bronchus.

• Stage 3: The cancer has spread to tissue near the lungs.

• Stage 4: The cancer has spread (metastasized) to another part of the body, the most common sites being the bones, brain, liver, or adrenal glands.

Healthcare providers will also use a more complex means of staging called TNM staging. With this, they will look at the size of the tumor (represented by a T); the number and locations of nodes affected (N); and whether the tumor has metastasized (M).⁴

What Are the Symptoms of Squamous Cell Carcinoma?

Common signs and symptoms of squamous cell carcinoma of the lung are not unlike those of other lung cancers. Symptoms typically include:⁵

• A persistent cough

• Shortness of breath

• Wheezing

• Coughing up blood 

• Fatigue

• Discomfort when swallowing

• Chest pain

• Fever

• Hoarseness

• Loss of appetite

• Unexplained weight loss of more than 5% over six to 12 months

But there's also a difference that distinguishes this form of cancer from others. Squamous cell carcinoma tends to cause symptoms earlier because it affects the larger airways of the lungs, as opposed to adenocarcinoma, which affects the edges.

This translates to higher rates of early detection, but 75% of cases are still only diagnosed after the cancer has spread.

Squamous cell carcinoma is the most common cause of Pancoast syndrome, also known as superior sulcus syndrome. Pancoast syndrome is caused by cancers that begin near the top of the lungs and invade nearby structures, such as nerves. Symptoms include:

• Shoulder pain that radiates down the inside of the arm

• Weakness or prickly sensations in the hands

• Flushing or sweating on one side of the face

• A droopy eyelid, called Horner’s syndrome

People with squamous cell carcinoma of the lung are also more likely to experience an elevated calcium level, or hypercalcemia.⁶ It is one of the symptoms of paraneoplastic syndrome and is caused by a tumor secreting a hormone-like substance that raises the calcium level in the blood.

This can cause dehydration, constipation, and kidney problems. It also can lead to mental confusion.

 Paraneoplastic Syndrome: Common Types and Symptoms

How Fast Does Squamous Cell Carcinoma Spread?

Metastasis (the spreading to another part of the body) with a squamous cell carcinoma of the lung depends on a number of factors, including your overall health and smoking history. The amount of time it takes to spread will vary with the individual and the stage of the cancer.

The spread of cancer is measured by how long it takes the cancer cells to double in size and mass at the primary site before it has metastasized. One study found the volume doubling time to be 149 days for squamous cell carcinoma of the lung, while the mass doubling time was 146 days.⁷

With non-small cell lung cancers, about 40% of cases will have spread beyond the lungs by the time they are diagnosed. Because squamous cell carcinoma is more likely to spread, it's harder to treat.⁸

Yale Medicine. Non-Small Cell Lung Cancer.

 What Is Metastasis?

What Are the Causes of Squamous Cell Carcinoma?

Squamous cell carcinomas are linked more strongly with smoking than other forms of non-small cell lung cancers. Overall, about 80% of all lung cancer cases in people assigned male at birth and 90% of those assigned female are associated with smoking.⁹

While squamous cell carcinomas are intrinsically linked to smoking, other causes can contribute.

Secondhand Smoke

Secondhand smoke presents a health risk to non-smokers. In addition to lung cancer, it can be the cause of other lung diseases including chronic obstructive pulmonary disease (COPD) and asthma.¹⁰

Secondhand smoke contains at least 70 toxins known to be carcinogenic (cancer-causing) and it can lead to other types of cancer too, including head and neck cancers.¹¹

Radon

Radon exposure in the home is the second leading cause of lung cancer overall. Radon gas can break down into tiny particles that lodge in the lungs and damage cells.

The Environmental Protection Agency estimates that about 21,000 people die each year as a result of radon-related lung disease, including squamous cell lung cancers.¹² Radon also is a risk factor in certain occupations, including uranium miners.¹³

Occupational Exposures

Asbestos exposure contributes to squamous cell lung cancer risk. Overall, the non-small cell lung cancer (NSCLC) subtypes account for at least 80% of these cases.¹⁴ Researchers continue to study the specific pathways in these asbestos-related lung cancers in the hopes of finding new treatment options.

Other occupational hazards that contribute to squamous cell lung cancer risk include heavy metals exposure. Toxins include:⁶

• Arsenic

• Vinyl chloride

• Nickel chromates

• Coal products

• Gasoline

• Diesel exhaust

Air Pollution

There is increasing recognition of the role that air pollution plays in lung cancer risk; the International Agency for Research on Cancer (IARC) defined it as a human carcinogen in 2013.¹⁵

Still, more studies are needed to better understand the specific impacts of particulate matter (PM2.5, PM10) on squamous cell carcinomas. The results have been mixed, with some studies suggesting a greater risk of adenocarcinoma lung cancers.¹⁵

Lung Disease

There's increasing evidence that COPD is, in and of itself, a risk factor for developing lung cancer. Both have some common features, like inflammation and long-term genetic damage.¹⁶ An underlying lung disease also may change how the disease progresses in someone who is diagnosed with squamous cell carcinoma.

Genetics itself may also play a role, given that the lung cancer risk is statistically increased in people who have other family members with lung cancer.¹⁷

Smoking and Adenocarcinomas

Cases of squamous cell carcinoma of the lungs have decreased in recent years but the rate of adenocarcinoma is up. The addition of filters to cigarettes allows smoke to be inhaled more deeply into the lungs where adenocarcinomas tend to develop.¹⁸ These cancers can, however, occur even in people who have never smoked.

How Is Squamous Cell Carcinoma Diagnosed?

Squamous cell carcinoma of the lungs is often first suspected when abnormalities are seen on an X-ray. Further evaluation may include:¹⁹

• Chest CT scan (a form of X-ray that produces cross-sectional images of the lungs)

• Sputum cytology (which tends to be effective given that cancer cells are more readily dislodged from the large airways)

• Bronchoscopy (a direct form of visualization in the lungs)

• PET scan (which is better able to detect current cancer activity)

• Endobronchial ultrasound (involving an ultrasound probe inserted into the windpipe)

Depending on the results, your healthcare provider may want to obtain a sample of tissue (lung biopsy) to confirm the diagnosis and will order further tests to check to see if your cancer has spread.

How Is Squamous Cell Carcinoma Treated?

Depending upon the stage of squamous cell carcinoma of the lungs, treatment may include:

• Surgery

• Chemotherapy

• Radiation therapy

• Targeted therapy

• Immunotherapy

• A combination of these treatments

Many clinical trials are in progress looking for new ways to treat this cancer and to help decide which treatments are most effective.

Oftentimes in the past, these different categories of treatment were used separately. For example, with metastatic squamous cell tumors, first-line therapy usually included either an immunotherapy drug or chemotherapy, but combination therapy may prove most beneficial.

 Combination Treatment With Chemoimmunotherapy

Surgery

Lung cancer surgery may be possible for squamous cell carcinoma in the early stages.²⁰ It may be considered in combination with other treatments, like chemotherapy and radiation therapy, in some stages as well.

Sometimes, a tumor may initially be inoperable but may be reduced in size with chemotherapy and/or radiation therapy so that surgery is then possible.

When chemotherapy is done to reduce the size of a tumor prior to surgery, it is referred to as "neoadjuvant chemotherapy." The use of immunotherapy to reduce the size of an inoperable tumor so that surgery may be performed also has proven successful.

 What Is Adjuvant Therapy?

Chemotherapy

Chemotherapy may be used alone, in conjunction with radiation therapy, or before or after surgery for lung cancer. It may also be combined with immunotherapy, and this combination appears to have the most benefit on survival in those who have metastatic disease.

For example, a 5-year follow-up study on the immunotherapy drug Keytruda (pembrolizumab) suggests a survival benefit (both overall and progression-free) when it is used during and after chemotherapy to treat squamous cell lung cancers.²¹ It's now a first-line treatment option.

Squamous cell carcinoma of the lungs responds somewhat differently to chemotherapy medications than other lung cancers, such as adenocarcinoma. The use of platinum-based drugs is more likely to achieve complete remission.²²

Common medications used initially for this type of cancer include:3

• Platinol (cisplatin)

• Paraplatin (carboplatin)

• Eloxatin (oxalaplatin)

• Gemzar (gemcitabine)²³

For those who respond to treatment, continuous (maintenance treatment) with Tarceva (erlotinib) or Alimta (pemetrexed) may be used.

Radiation Therapy

Radiation therapy may be used to treat cancer or to control symptoms related to the spread of cancer. Radiation may be given externally, or internally (brachytherapy) in which radioactive material is delivered to a precise area of the lungs during a bronchoscopy.

Targeted Therapy

Targeted drugs are to treat EGFR mutations in lung adenocarcinoma. EGFR, or epidermal growth factor receptor, is a protein involved in driving the growth of a cancer. Squamous cell carcinoma of the lungs may also be treated by targeting the EGFR pathway, but by using a different mechanism.

Instead of targeting EGFR mutations, anti-EGFR antibodies are a class of drugs used to bind to EGFR on the outside of cancer cells. When EGFR is thus bound, the signaling pathway which tells the cell to grow is halted.

Portrazza (necitumumab) may be used along with chemotherapy for advanced squamous cell cancers.²⁴ Gilotrif (afatinib), another type of targeted therapy, is also used with chemotherapy, specifically in cases where a person is not eligible for immunotherapy. This type of treatment is most commonly prescribed for people with epidermal growth factor genetic aberrations.²⁵

Immunotherapy

Immunotherapy drugs were first approved for the treatment of lung cancer in 2015. The immunotherapy drugs have been approved for SCC of the lungs, used as monotherapy or in combination with other treatments. These immunotherapy drugs include:²⁶

• Opdivo (nivolumab)

• Keytruda (pembrolizumab)

• Imfinzi (durvalumab)

• Tecentriq 410 (atezolizumab)

• Imjudo (tremelimumab)

These treatments enhance the immune system's ability to fight off cancer cells.²⁷

To understand how these drugs work, it may help to think of your immune system as a car. The "brakes" are controlled by a protein called PD-1. Drugs like Opdivo in this analogy work to block PD-1 to allow the immune system to fight against the cancer without interference—in essence, taking the brakes off the car.

Immunotherapeutic drugs are currently approved for people with a metastatic non-small cell lung malignancy whose cancer has progressed during or after platinum-based chemotherapy.

As noted above, for metastatic squamous cell carcinoma, the combination of Keytruda and chemotherapy greatly improved survival.

What Is the Prognosis of Squamous Cell Carcinoma?

Keep in mind that statistics describe the “average” course or survival. Ultimately, each person is different. Many factors can affect the prognosis of squamous cell lung cancer including your age at diagnosis, your sex, the condition of your general health, and how you respond to treatments.

For example, the five-year survival rate for non-small cell lung cancer is based on people who were diagnosed five years earlier. Since many significant treatments for squamous cell cancer of the lung may have been approved after those individuals were diagnosed, statistics do not necessarily indicate how someone diagnosed today will do.²⁸

Current five-year survival rates for non-small cell lung cancer diagnosed between 2012 and 2018 are 65% for localized cancer that hasn't spread. It's just 9% for metastatic cancers, with an overall rate of 28% across the stages.²⁹

Most lung cancers, including squamous cell carcinoma of the lung, are detected after they have spread and so are difficult to treat. The diagnosis is serious, but early detection and newer treatments are helping to extend survival for people living with lung cancer.³⁰

Coping With Squamous Cell Carcinoma

A diagnosis of squamous cell carcinoma of the lungs is frightening and you may feel very alone. This is the time to reach out and allow your friends and loved ones to support you. 

Studies show that people who better understand their cancer not only feel more empowered, but that knowledge can sometimes make a difference in survival as well.³¹

Not all oncologists may be familiar with the latest studies. Since general oncologists may not be abreast of fast-changing research, many lung cancer survivors recommend obtaining a second opinion from one of the larger National Cancer Institute-designated cancer centers.

See if you can find a support group for people with lung cancer in your community or connect with a lung cancer community online. Check out the lung cancer organizations such as LUNGevity, the American Lung Association Lung Force, and the Lung Cancer Alliance.

When searching for others with lung cancer on social media, the hashtag is #LCSM which stands for lung cancer social media. If you are under the age of 50, check out the Bonnie J. Addario Lung Cancer Foundation, an organization that takes a special interest in lung cancer in young adults.

Summary

Squamous cell carcinoma of the lung is commonly associated with smoking and accounts for about 30% of all non-small cell lung cancers, which constitute the majority of smoking-related cancers. Yet others can develop squamous cell carcinoma too, including people exposed to radon, asbestos, secondhand smoke, and air pollution.

The treatment choices and outlook after a squamous cell lung cancer diagnosis depend on a number of factors, including the metastasis (spread) of the cancer and a person's overall health. Generally, though, the long-term prognosis is poor, but some studies find differences depending on the cancer subtype.²

Research and treatments for squamous cell carcinoma of the lung are changing rapidly, and many survivors are currently alive because they educated themselves. It's important to become an advocate for your health and learn about your disease and treatment options.