Definition/General
Introduction:
Cervical squamous cell carcinoma is the most common type of cervical cancer, arising from the transformation zone of the cervix
It represents approximately 80-85% of all cervical cancers and is strongly associated with high-risk human papillomavirus (HPV) infection.
Origin:
Arises from the squamous epithelium of the ectocervix, typically at the transformation zone
Develops through progressive sequence from normal epithelium to CIN (cervical intraepithelial neoplasia) to invasive carcinoma.
Classification:
WHO Classification recognizes keratinizing and non-keratinizing subtypes
FIGO staging system used for clinical staging
TNM staging also applicable.
Epidemiology:
Peak incidence 45-55 years
Major cause of cancer mortality in developing countries
Strong association with HPV types 16, 18, 31, 33, 45
Preventable by HPV vaccination and screening.
Clinical Features
Presentation:
Abnormal vaginal bleeding (post-coital, intermenstrual, postmenopausal)
Abnormal Pap smear
Visible cervical lesion
Pelvic pain in advanced stages.
Symptoms:
Vaginal bleeding (most common)
Vaginal discharge (watery, bloody, foul-smelling)
Pelvic or back pain
Leg swelling
Urinary or bowel symptoms in advanced disease.
Risk Factors:
High-risk HPV infection (major risk factor)
Multiple sexual partners
Early sexual activity
Immunosuppression
Smoking
Long-term oral contraceptive use
Multiple pregnancies.
Screening:
Pap smear (cytology)
HPV testing
Co-testing (cytology + HPV)
Colposcopy for abnormal results
Visual inspection with acetic acid (VIA) in resource-limited settings.
Master Cervical Squamous Cell Carcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Exophytic, ulcerative, or infiltrative lesion
May be polypoid, papillary, or crater-like
Friable and easily bleeding
Variable size from small erosions to large masses.
Characteristics:
Size variable (few mm to >5 cm)
Irregular surface
Firm to hard consistency
Gray-white to tan coloration
May involve entire cervix.
Size Location:
Usually arises from transformation zone
May extend to vaginal fornices
Can involve parametrium in advanced cases
Bilateral spread possible.
Multifocality:
Usually unifocal but may be multifocal
Skip lesions possible
Involvement of upper genital tract in advanced disease.
Microscopic Description
Histological Features:
Invasive squamous epithelium showing varying degrees of differentiation
Keratinization present in well-differentiated tumors
Intercellular bridges and keratin pearls may be seen.
Cellular Characteristics:
Polygonal cells with eosinophilic cytoplasm
Nuclear pleomorphism and hyperchromatism
Prominent nucleoli
High mitotic activity including atypical mitoses.
Architectural Patterns:
Infiltrative growth with destruction of normal architecture
Nested, trabecular, or solid growth patterns
Stromal desmoplasia
Lymphovascular invasion common.
Grading Criteria:
Grade 1 (well-differentiated): >75% keratinization
Grade 2 (moderately differentiated): 25-75% keratinization
Grade 3 (poorly differentiated): <25% keratinization.
Immunohistochemistry
Positive Markers:
p16 diffuse positive (surrogate for HPV)
CK5/6 positive
p63 positive
CK7 variable
EMA variable.
Negative Markers:
CK20 usually negative
TTF-1 negative
CDX2 negative
PAX8 negative
Neuroendocrine markers negative.
Diagnostic Utility:
p16 block positivity indicates high-risk HPV infection
CK5/6 and p63 confirm squamous differentiation
Helps distinguish from adenocarcinoma.
Molecular Subtypes:
HPV-associated (>90%)
HPV-independent (rare)
Different HPV types may show varying behavior.
Molecular/Genetic
Genetic Mutations:
HPV integration into host genome
E6 and E7 oncoproteins inactivate p53 and Rb
PIK3CA mutations
KRAS mutations
TP53 mutations in HPV-negative tumors.
Molecular Markers:
HPV DNA detection by PCR or in situ hybridization
p16 overexpression
Loss of p53 and Rb function
High Ki-67 proliferation index.
Prognostic Significance:
HPV status affects prognosis
Tumor size, stage, and lymph node involvement most important
High-grade histology predicts worse outcome.
Therapeutic Targets:
HPV-targeted immunotherapy
Immune checkpoint inhibitors (pembrolizumab)
Bevacizumab for recurrent disease
Targeted therapy based on molecular profile.
Differential Diagnosis
Similar Entities:
Cervical adenocarcinoma
Adenosquamous carcinoma
Metastatic squamous carcinoma
Cervical intraepithelial neoplasia (CIN)
Condyloma acuminatum.
Distinguishing Features:
Squamous cell carcinoma: p63+, CK5/6+
Adenocarcinoma: CEA+, CK7+
CIN: Non-invasive, basement membrane intact
Condyloma: HPV 6/11, no invasion.
Diagnostic Challenges:
Small biopsy specimens
Distinction from high-grade CIN
Mixed tumors (adenosquamous)
Microinvasive vs invasive carcinoma.
Rare Variants:
Verrucous carcinoma
Warty carcinoma
Papillary squamous carcinoma
Lymphoepithelioma-like carcinoma
Squamous carcinoma with sarcomatoid features.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
[diagnosis name]
Classification
Classification: [classification system] [grade/type]
Histological Features
Shows [architectural pattern] with [nuclear features] and [mitotic activity]
Size and Extent
Size: [X] cm, extent: [local/regional/metastatic]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [marker]: [result]
Molecular: [test]: [result]
[other study]: [result]
Prognostic Factors
Prognostic factors: [list factors]
Final Diagnosis
Final diagnosis: [complete diagnosis]