Cervical Cancer for MBBS Students

Study Notes

Cervical carcinoma (CC) is a malignant tumour found in the tissues of the cervix, with an estimated 660,000 new cases and 350,000 deaths in 2022 globally.
CC is the 4th most common cancer in women globally, with the highest rates of incidence and mortality in low- and middle-income countries due to lack of access to national HPV vaccination, cervical screening, and treatment services.
Women living with HIV are 6 times more likely to develop CC compared to women without HIV.

Cervical dysplasia, also known as cervical intraepithelial neoplasia (CIN), is a precancerous condition in which abnormal cells grow on the surface of the cervix.
CIN is not cancer but may become cancer, with most cases occurring at the squamocolumnar junction of the cervix.
CIN can also occur in vaginal walls and vulvar epithelium.

CIN 1: abnormal cells affecting about one-third of the thickness of the epithelium, which rarely becomes cancer and often goes away on its own.
CIN 2: abnormal cells affecting about one-third to two-thirds of the epithelium, which are more likely to require treatment to prevent cancer.
CIN 3: abnormal cells affecting more than two-thirds of the epithelium, which are also more likely to require treatment to prevent cancer.
CIS (carcinoma in situ): severe neoplastic changes that are high likely to be cancer, but still a dysplasia.

The Bethesda reporting system describes abnormal changes to squamous cells in the cervix as squamous intraepithelial lesions (SIL) into low grade (LSIL) and high grade (HSIL).
CIN 1 corresponds to LSIL, while CIN 2 and 3 correspond to HSIL.

Mode of transmission: sexual intercourse (contact transmission).
Site: may affect the genitals, including vulva, vagina, cervix, penis, scrotum, rectum, and anus.
Clinical presentation: painless, itching, burning sensation, postcoital bleeding, vaginal discomfort, and discharge.
Risk Factors: multiple sexual partners, unprotected sex, smoking, compromised immune system.
HPV variants that cause cancer do not cause warts (only condyloma acuminatum).

Female with multiple sexual partners.
Male partner with multiple sexual partners.
Young age at first intercourse (before 17 yo).
Persistent infection with a high oncogenic risk HPV (e.g., HPV 16/18).
Immunosuppression.
Certain HLA subtypes.
Use of oral contraceptives (>10 y).
Use of nicotine/smoking.
Others: genital infection, family history, lack of circumcision in male partner.

Common: vaginal bleeding, vaginal discharge, pelvic pain, dysuria, and constitutional symptoms.
May extend by direct spread to involved adjacent tissues, such as paracervical tissues, urinary bladder, ureters, rectum, and vagina, as well as lymph nodes and distant metastases.

Gross: fungating (exophytic), ulcerative, infiltrative, or flat lesions.
Microscopic:
- Squamous cell carcinoma: nests and tongues of malignant squamous epithelium invading the underlying stroma.
- Adenocarcinoma: proliferation of glandular epithelium composed of malignant endocervical cells with large hyperchromatic nuclei and relatively mucin-depleted cytoplasm.
- Adenosquamous carcinomas: intermixed glandular and malignant squamous epithelium.
- Neuroendocrine carcinomas: relatively small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern), and absent or inconspicuous nucleoli.

Local spread (direct extension) to parametrium and surrounding structures, including vagina, bladder, and rectum.
Ureteral compression leads to hydroureter, hydronephrosis, and renal failure (most common cause of death, 50%).
Bilateral ureteric obstruction leads to obstructive nephropathy.
Spread to lower uterine segment and uterine cavity.

Prevention: routine cervical screening (Pap Smear) for females >20 yo, nationwide HPV vaccination program, and HPV DNA test for suspected cases.
Patients with abnormal cytology or symptoms are referred to examination by colposcopy.
Adjunct imaging can be useful (pelvic ultrasound, MRI).
Definitive diagnosis requires tissue biopsy.

Stage I: confined to the cervix only.
Stage II: CC invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall.
Stage III: CC involves the lower third of the vagina, and/or extends to the pelvic wall and/or causes hydronephrosis or non-functioning kidney.
Stage IV: CC extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum.

Treatment plan differs according to each stage of CC.
Stage I: cone biopsy of cervix.
Stage II-IV: hysterectomy (partial/total) and/or irradiation for extensive lesions.
Prognosis depends on staging: Stage IV (extension beyond pelvis) has poorer prognosis.
Prognosis depends on cell type: neuroendocrine carcinoma has poorer prognosis.