What organs are prone to developing squamous cell cancer?

Organs That Can Develop Squamous Cell Carcinoma

Squamous cell carcinoma arises from any organ lined by squamous epithelium or tissues capable of squamous differentiation, with the most common sites being the skin, head and neck (oral cavity, pharynx, larynx), esophagus, lungs, cervix, and bladder.

Primary Anatomical Sites

Skin and Cutaneous Structures

• The skin is the most common site, with cutaneous SCC being the second most common skin cancer after basal cell carcinoma 1
• Cutaneous SCC arises from keratinizing cells of the epidermis or its appendages 1
• The vermilion border of the lip is also a common cutaneous site 1

Head and Neck Region

• The oral cavity, pharynx (oropharynx and hypopharynx), and larynx are major sites where SCC arises from epithelial cells 1
• Squamous cell carcinoma of the head and neck (SCCHN) is the seventh most common cancer worldwide with approximately 700,000 new cases annually 1
• The tongue is a particularly common site within the oral cavity, with SCC accounting for more than 90% of all malignant tongue tumors 2
• HPV-positive oropharyngeal SCC represents 30-35% of oropharyngeal cancers globally, with approximately 72% of newly diagnosed head and neck cancer patients being HPV-positive 3

Respiratory Tract

• The lungs develop squamous cell carcinoma as one of the major subtypes of non-small cell lung cancer (NSCLC) 4
• The larynx, as part of the upper respiratory tract, is a common site with an annual crude incidence rate of 4.6/100,000 in Europe 1

Gastrointestinal Tract

• The esophagus is a major site, with squamous cell cancer being the most common neoplasm of the esophagus worldwide 5
• Esophageal squamous cell carcinoma (ESCC) shows enormous variation in global incidence 5

Genitourinary Tract

• The urinary bladder can develop squamous cell carcinoma, though it represents only 3% of urinary tumors diagnosed in the United States 1
• The diagnosis of bladder squamous cell tumors requires the presence of keratinization in the pathologic specimen 1
• The distal third of the urethra, which is dominated by squamous epithelium, can develop SCC 1
• The penis, vulva, and anus can also develop SCC, though these are typically managed with specialized protocols 1

Cervix

• The cervix is a well-established site for squamous cell carcinoma, particularly associated with HPV infection 4

Common Molecular and Pathologic Features

Epithelial Origin

• All SCCs arise from epithelial cells with squamous differentiation potential 1, 4
• SCCs can originate from stratified squamous epithelium or from simple/pseudo-stratified epithelia through activation of quiescent cells and cell-fate switching 6

Shared Risk Factors Across Sites

• Tobacco and alcohol account for 75-85% of SCCHN and are major risk factors across multiple sites 1, 2, 7
• HPV infection (particularly HPV-16) is a common risk factor among major SCCs including non-melanoma skin cancer (NMSC), head and neck SCC (HNSC), esophageal SCC (ESCC), and lung SCC (NSCLC) 4
• Chronic UV exposure is the primary risk factor for cutaneous SCC 1
• Immunosuppression increases risk across all anatomical sites 1, 7

Clinical Implications

Site-Specific Prognosis

• Five-year relative survival varies significantly by anatomical site: laryngeal SCC (61%), oral cavity SCC (49%), oropharyngeal SCC (41%), and hypopharyngeal SCC (25%) 1
• Cutaneous SCC has variable metastatic potential depending on size, depth, and location 1

Unified Disease Perspective

• Despite arising from different anatomical sites, SCCs share many phenotypic and molecular characteristics, including abnormalities in cell-cycle regulation and signal transduction 4, 6
• This commonality suggests that molecular insights and therapeutic targets discovered for one SCC site may be applicable to others 4, 6