PREMALIGNANT LESIONS AND CARCINOMA OF THE UTERINE CERVIX

Question 1

INTRODUCTION

Answer 1

Carcinoma of the cervix is the 2nd commonest cancer among women worldwide
Cervical cancer is preventable
3-4cm in length, 2.5-3.5 in diameter

Covered by 2 types of epithelium
Ectocervix: stratified NK squamous epithelium
Endocervix: columnar epithelium
The endocervical canal lined with columnar epithelium which secretes mucus to help with lubrication

At the upperlimit of the endocervical canal its merges with the endometrial epithelium in the body of the uterus and at its lower limit it meets with the squamous epithelium at the SCJ(Squamocolumnar junction)

Question 2

THE SCJ(SQUAMOCOLUMNAR JUNCTION)

Answer 2

Location varies with age and hormonal status

Everts outward to ectocervix during Adolescence, pregnancy and use of combination hormonal contraceptives

Regresses to endocervical canal with Menopause and other low estrogen states e.g prolonged lactation and use of Progestin-only contraceptives

The rise in estrogen level at puberty leads to the glycogenation of the Non keratinized squamous epithelium, the glucogen provides carbohydrate for Lactobacilli which dominate normal vaginal flora in reproductive aged women,
The lactobacilli thus produces lactic acid lowering the PH to less than 4.5, this reduction in PH leads to squamous metaplasia
Squamous metaplasia occurs most actively immediately adjacent to the SCJ creating a zone of METAPLASTIC EPITHELIUM termed the TRANSFORMATION ZONE(TZ)

Question 3

TZ AND CERVICAL NEOPLASM

Answer 3

Nearly all cervical neoplasia both squamous and columnar develop within the transformation zone, usually adjacent to the new SCJ

Theoretically cervical cells undergoing metaplasia are particularly vulnerable to the oncogenic effects of HPV and co-carcinogens

Metaplasia is most active during Adolescence and Pregnancy

Question 4

CLASSIFICATION SYSTEM FOR PREMALIGNANT SQUAMOUS CERVICAL LESIONS

Answer 4

CIN=Cervical Intraepithelial Neoplasia
SIL= Squamous Intraepithelial Lesion

Mild Dysplasia - CIN I - Low grade SIL
Moderate - CIN II - High grade SIL
Severe - CIN III - High grade SIL

Carcinoma - CIN III - High grade SIL
In situ

SQUAMOUS INTRAEPITHELIAL LESIONS

In LSIL, 60% Regress, 30% Persists and 10% progresses to HSIL

In HSIL, 30% Regresses, 60% Persists and 10% progresses to Carcinoma

Question 5

BETHESDA SYSTEM

Answer 5

The precursor lesion that arises from the columnar epithelium is referred to as AIS
ADENOCARCINOMA IN SITU

In AIS normal columnar epithelium is replaced by abnormal epithelium showing abnormal irregularly arranged cells with increased size of cells and nuclei, nuclear hyperchromasia, mitotic activity and cellular stratification

Question 6

AETIOPATHOGENESIS

Answer 6

High risk HPV is a major etiological factor
Multiple sexual partners
Young age at first sexual relationship
High parity
Immunosuppression
Smoking
Prolonged use of oral contraceptives 
Coitus with uncircumcised men
Socioeconomic status

Question 7

PATHOGENESIS

Answer 7

The virus HPV infects the metaplastic cells at the SCJ but replicate in mature squamous cell by inducing DNA synthesis resulting in Nuclear atypia and Cytoplasmic Perinuclear Halo

Studies have shown that HPV replicates by interfering with both Rb and P53 tumor suppressor genes

2 HPV protein; E6 and E7
Binding of oncogene E6 to P53 upregulate its activity by rapid degeneration of P53 thus interrupting the cell death pathway and prevent Senescence

Binding of the E7 protein to Rb promotes its Proteolysys and induce E7 activity to promote cell cycle entry jnto the S phase

HPV also infects glands and Neuroendocrine cells present in cervical mucosa resulting in Malignant transformation adenocarcinoma and neuroendocrine carcinoma

Question 8

MORPHOLOGY

Answer 8

CERVICAL CARCINOMA

1. Squamous cell carcinoma: commonest, 80% of cases, precursor lesion HSIL
2. Cervical Adenocarcinoma: 15%, prefursor lesion AIS( Adenocarcinoma in situ)
3. Adenosquamous and Neuroendocrine carcinoma: rare tumor with poor prognosis

HISTOLOGY:
1. Squamous cell tumor shows nest and strands of malignant squamous epithelium invading the cervical stroma

2. Adenocarcinoma shows proliferating glands composed of malignant endocervical cells having large hypochromatic nuclei
3. Adenosquamous is composed of a mixture of both 1&2
4. Neuroendocrine carcinoma shows similar features of small cell carcinoma of lung cancer

Question 9

INVESTIGATIONS

Answer 9

• 1. Pap smear
• 2.Virtual inspection with 5% acetic acid or with lugols iodine(VIA OR VILI)
• 3.Colposcopy examination.
• 4.HPV DNA testing.
• 5.Cone biopsy
• 6. Cervicography.
• 7. Polar probe.

Question 10

TREATMENT

Answer 10

Cone biopsy curative for microinvasive tumor

Hysterectomy with Lymph node dissection for advanced cases

Question 11

PREVENTION/SCREENING

Answer 11

Cervical prevention and control includes the following components:
•1.Cervical screening and management Of abnormal pap smear.
•2.Histologic diagnosis and removal of precancerous lession.
•3. Surgical removal of invasive lession and adjuvant radiation therapy and chemotherapy.
•4. HPV vaccination program.

SCREENING GUIDELINES FOR EARLY DETECTION OF CERVICAL CANCER

Screening should begin approximately 3 years after a woman begins having vaginal intercourse, but no later than 21 years of age

•Screening should be done every year with regular Pap tests or every 2 years using liquid-based tests

At or after the age of 30, women who have had 3 normal results may get screened every 2-3 years unless doctor deems she has risk factors

Women 70 years and older who have had three or more consecutive Pap tests in the last 10 years may choose to stop cervical cancer screening

•Screening after a total hysterectomy (with removal of the cervix) is not necessary unless the surgery was done as a treatment for cervical cancer