Saturday, December 20, 2025

Cervical Squamous Cell Carcinoma: Epidemiology, Etiology, Pathogenesis, Histopathology, Symptoms, Staging, Diagnosis, Management and Prevention

Cervical Squamous Cell Carcinoma

~Introduction


Cervical squamous cell carcinoma (SCC) is the most common malignant tumor of the cervix, accounting for approximately 70–80% of all cervical cancers worldwide. It arises from the squamous epithelium of the ectocervix, usually at the transformation zone, where squamous epithelium meets glandular epithelium. Cervical cancer remains a major public health problem, especially in developing countries, despite being largely preventable through screening and vaccination.

Persistent infection with high-risk human papillomavirus (HPV) is the single most important etiological factor. Cervical SCC has a long precancerous phase, which allows early detection and treatment, significantly reducing mortality.

~Epidemiology

  • Cervical cancer is the fourth most common cancer in women worldwide

  • Higher incidence in low- and middle-income countries

  • Peak incidence: 45–55 years

  • Squamous cell carcinoma is more common than adenocarcinoma

  • Major cause of cancer-related death among women in developing nations

~Etiology and Risk Factors

Human Papillomavirus (HPV)

  • High-risk HPV types:

    • HPV 16 (most common)

    • HPV 18, 31, 33, 45

  • Persistent infection leads to malignant transformation

Other Risk Factors

  • Early age at first sexual intercourse

  • Multiple sexual partners

  • High parity

  • Poor genital hygiene

  • Smoking (carcinogenic effect on cervical epithelium)

  • Immunosuppression (e.g., HIV infection)

  • Long-term use of oral contraceptives

  • Low socioeconomic status

~Pathogenesis

Cervical squamous carcinoma develops through a well-defined sequence of precancerous lesions:

  1. HPV infection

  2. Cervical Intraepithelial Neoplasia (CIN)

  3. Invasive carcinoma

Molecular Mechanism

  • HPV infects basal epithelial cells

  • Viral oncogenes E6 and E7:

    • E6 inactivates p53

    • E7 inactivates RB protein

  • Leads to:

    • Loss of cell cycle control

    • Genomic instability

    • Malignant transformation

~Precancerous Lesions: Cervical Intraepithelial Neoplasia (CIN)

GradeDescription
CIN IMild dysplasia (lower 1/3 epithelium)
CIN IIModerate dysplasia (lower 2/3 epithelium)
CIN IIISevere dysplasia to carcinoma in situ

Untreated CIN III can progress to invasive carcinoma over several years.

~Gross Pathology

The tumor commonly arises in the transformation zone.

Gross Appearances

  • Exophytic (fungating) growth

  • Ulcerative lesion

  • Infiltrative mass

  • Advanced tumors may involve:

    • Vagina

    • Parametrium

    • Bladder

    • Rectum

~Histopathology

Microscopic Features

  • Invasive nests and cords of malignant squamous cells

  • Features include:

    • Pleomorphic cells

    • Hyperchromatic nuclei

    • Increased mitotic figures

    • Loss of normal stratification

Keratinization

Based on keratin formation, SCC is divided into:

1. Keratinizing Squamous Cell Carcinoma

  • Keratin pearls present

  • Intercellular bridges

  • Better differentiated

2. Non-keratinizing Squamous Cell Carcinoma

  • No keratin pearls

  • Sheets of malignant cells

  • Poorly differentiated

~Clinical Features

Early Stage

  • Often asymptomatic

  • Detected through screening (Pap smear)

Symptoms in Advanced Disease

  • Abnormal vaginal bleeding:

    • Postcoital

    • Intermenstrual

    • Postmenopausal

  • Foul-smelling vaginal discharge

  • Pelvic pain

  • Dyspareunia

  • Weight loss and anemia in late stages

~Spread of Disease

Local Spread

  • To vagina

  • Parametrium

  • Uterus

Lymphatic Spread

  • Pelvic lymph nodes:

    • Iliac

    • Obturator

    • Sacral nodes

Hematogenous Spread

  • Late occurrence

  • Lungs

  • Liver

  • Bone

~Staging (FIGO Staging – Simplified)

StageDescription
IConfined to cervix
IIBeyond cervix but not pelvic wall
IIIPelvic wall or lower vagina involved
IVAdjacent organs or distant metastasis

Staging is clinical, not surgical.

~Diagnosis

Screening Methods

  • Pap smear (Papanicolaou test)

  • Liquid-based cytology

  • HPV DNA testing

Diagnostic Tests

  • Colposcopy

  • Cervical biopsy

  • Cone biopsy for early lesions

~Management

Early-Stage Disease

  • Conization

  • Radical hysterectomy

  • Fertility-sparing surgery in selected cases

Advanced Disease

  • Radiotherapy

  • Concurrent chemoradiation (cisplatin-based)

Metastatic Disease

  • Palliative chemotherapy

  • Supportive care

~Prognosis

Prognosis depends on:

  • Stage at diagnosis

  • Tumor size

  • Lymph node involvement

  • Depth of stromal invasion

Five-Year Survival Rate

  • Stage I: ~80–90%

  • Stage II: ~60%

  • Stage III: ~30%

  • Stage IV: <15%

~Prevention

Primary Prevention

  • HPV vaccination:

    • Bivalent

    • Quadrivalent

    • Nonavalent vaccines

  • Safe sexual practices

Secondary Prevention

  • Regular cervical screening

  • Early treatment of CIN

~Complications

  • Obstructive uropathy

  • Fistula formation (vesicovaginal, rectovaginal)

  • Severe anemia

  • Cachexia

  • Psychological distress

~Conclusion

Cervical squamous cell carcinoma is a preventable and treatable malignancy when detected early. Persistent infection with high-risk HPV plays a central role in its development. Effective screening programs, HPV vaccination, and timely treatment have significantly reduced disease burden in developed countries. Strengthening awareness, vaccination coverage, and screening services remains crucial to reducing morbidity and mortality, especially in developing regions.


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