Squamous cell carcinoma (SCC) is a type of cancer that arises from squamous cells, which are flat, thin cells found in the outer layer of the skin and lining of various organs such as the mouth, throat, lungs, and cervix. Understanding what causes squamous cell carcinoma involves exploring a complex interplay of environmental exposures, genetic changes, infections, and cellular processes that disrupt normal cell growth and lead to cancer.
At its core, squamous cell carcinoma develops when the normal regulatory mechanisms that control cell division and death become impaired. Squamous cells normally grow, divide, and die in a controlled manner, but when this balance is disturbed, cells can begin to multiply uncontrollably, forming tumors. Several factors contribute to this disruption.
One of the primary causes of squamous cell carcinoma is **exposure to ultraviolet (UV) radiation** from the sun or tanning beds. UV radiation damages the DNA in skin cells, causing mutations that can accumulate over time. These mutations affect critical genes that regulate cell growth and repair, such as tumor suppressor genes. When these genes are damaged, cells lose their ability to repair DNA or undergo programmed cell death (apoptosis), allowing mutated cells to survive and proliferate. This is why SCC is common in sun-exposed areas like the face, ears, and hands.
**Tobacco use** is another major cause, especially for squamous cell carcinomas that develop in the mouth, throat, and lungs. Chemicals in tobacco smoke cause DNA damage and chronic inflammation, which promotes mutations and cancer development. Alcohol consumption can also increase risk, particularly when combined with tobacco, by further irritating and damaging the mucous membranes.
Certain **viral infections** play a significant role in causing squamous cell carcinoma in specific locations. For example, **human papillomavirus (HPV)** infection is strongly linked to SCC of the oropharynx (throat) and genital areas. HPV produces proteins that interfere with the cell’s tumor suppressor proteins, such as p53 and retinoblastoma protein (pRb). These viral proteins disable the cell’s ability to control growth and repair DNA, leading to unchecked cell division and cancer formation. Similarly, **Epstein-Barr virus (EBV)** is associated with nasopharyngeal carcinoma, a type of SCC in the upper throat behind the nose.
**Chronic inflammation and irritation** can also contribute to SCC. Conditions that cause long-term skin irritation or injury, such as scars from burns, chronic ulcers, or certain skin diseases, create an environment where cells are constantly dividing to repair damage. This repeated cell turnover increases the chance of mutations and cancer development.
Genetic factors can influence susceptibility to squamous cell carcinoma. Some people inherit mutations in genes that normally protect against cancer, making them more vulnerable when exposed to environmental risks. For example, mutations in the TP53 gene, which encodes the p53 tumor suppressor protein, are common in SCC and lead to loss of cell cycle control.
Radiation exposure, whether from medical treatments or environmental sources, can also cause DNA damage that leads to SCC. This is especially relevant for people who have had radiation therapy for other cancers or who have been exposed to high levels of radiation occupationally.
At the molecular level, squamous cell carcinoma involves multiple genetic and epigenetic changes. These include mutations in oncogenes (genes that promote cell growth) and tumor suppressor genes, as well as changes in DNA methylation patterns that alter gene expression. The viral oncoproteins from HPV, for example, cause degradation of p53 and inhibition of pRb, disabling key checkpoints that normally prevent cancer.
In some cases, squamous cell carcinoma cells produce substances like parathyroid hormone-related protein (PTHrP), which can affect the body beyond the tumor itself, contributing to symptoms such as hypercalcemia. This reflects how cancer cells can manipulate their environment to support their growt
