Cervical Cancer

CANCER OF THE CERVIX

INTRODUCTION

Every 2 minutes one woman dies from cervical cancer. Worldwide, invasive cervical cancer is the most common genital female malignancy. It is the 2nd most common malignancy in women after breast cancer. In developing countries the lifetime risk of invasive cancer of the cervix is 3%.

500,000 new cases are reported per year worldwide. 80% majority being in developing countries. In Kenya, data from hospital based registers in Nairobi indicate ca cervix accounted for 70-80% of all cancers of genital tract.

The 5 year survival rate for all stages combined in developed countries is 72% while in developing countries is 48%. Incidence in black women is 50% higher with a lower survival rate. Carcinoma in situ (Cis) is common in 25-34 years. Invasive disease is common in females more than 50year old. It is uncommon in those less than 25years.

ANATOMY

The cervix is the lower 1/3 of the uterus and is composed of dense fibromuscular tissue lined by 2 types of epithelium. The lower part of cervix (ectocervix) lies within the vagina and is visible with a speculum. The upper 2/3 (endocervix) lies above the vagina.

Cervical canal runs from the internal os (opening) leading into the uterine cavity to the external os which is the opening visualized on the speculum.

Squamous epithelium lines most of the ectocervix and vagina. Columnar epithelium lines the cervical canal. Transformation zone is the area where columnar epithelium is being replaced or has been replaced by squamous epithelium. The transformation zone is that portion of cervix that is visible during speculum examination.

PATHOLOGY

90% of cancer of the cervix arises from the transformational zone. The transformational zone is larger during puberty and pregnancy. Cervical cells from this zone undergo dysplasia which is lack of normal maturation of cells as they migrate from the basal layer to the superficial layer. This dysplastic picture is referred to as cervical intraepithelial neoplasia (CIN).

CIN is graded into CIN 1, CIN 11, and CIN 111 depending on the degree of involvement of the epithelium.

HPV infection and CIN 1 are regarded as Low grade squamous intraepithelial neoplasia (LSIL).

CIN 11 and CIN 111 are regarded as High grade squamous intraepithelial neoplasia (HSIL).

Histopathological types of invasive cancers are:

  • Squamous cell carcinoma: 80-90% of all cervical malignancies
  • Adenocarcinoma: 5-20% arising from the endocervical cells

Rare cancers include mixed carcinomas, small cell carcinoma and metastatic tumors.

RISK FACTORS

  • Onset of sexual activity at an early age
  • Sexual promiscuity
  • High parity
  • Race
  • Low social economic status
  • Tobacco smoking
  • HPV infection 16/18 strains: 10-30% of sexually active women have acquired HPV infection by the age of 30.
  • Immunesuppresion
  • Long term use of COCs > 5 yrs

HUMAN PAPILLOMA VIRUS INFECTION

Persistent infection with high risk HPV is a major cause of cervical cancer. About 13 types of HPV are regarded as high risk with HPV 16/18 being the most implicated.

HPV 6/11 are associated with benign genital warts and are classified as low risk. HPV infection is common in young women but most resolve spontaneously within 6-24 months. Only those that persist long term pose a risk for development of cancer.

Human papilloma virus

High risk types:16,18,31,33,39,45,51,52,56,58,59,68,73,82,

Low risk types :6,11,40,42.43,44,54,61,70,72,81,CP6108,26,53.66

Graph

SCREENING FOR CERVICAL CANCER

Aim is to detect precancerous changes. Those with abnormalities will need follow up, diagnosis and treatment. The screen test chosen should be accurate, reproducible, inexpensive, easy to perform, safe and acceptable.

Screen tests available include:

-Cytological tests- conventional (Pap smear) and Liquid based

-HPV DNA testing

- Acetic acid: abnormal cervical epithelium temporarily turns white.

-Lugols iodine: Precancerous/cancerous lesion appears as well defined thick yellow colored (mustard) lesion. Normal squamous epithelium stains brown or black and columnar stains pink.

MANAGEMENT OF PREMALIGNANT LESIONS

In all women with abnormal screen test further investigation is needed in order to make a definitive diagnosis.Histopathological examination of tissue obtained through biopsy guided by colposcopy is the standard method.

All biopsy confirmed CIN II and CIN III lesions should be treated. CIN 1 lesions are more likely to resolve and Pap smear should be repeated after 6 months. If progression is noted or in older women whom regression is less likely, treatment should be offered.

Treatment options include:

  • Ablative mechanisms: This is through destroying abnormal tissue by heating or freezing.
  • Excision mechanism: Surgically removing abnormal tissue
  • CRYOTHERAPY: It’s an ablative method that eliminates precancerous areas by freezing them.
  • Loop Excision Electrosurgical Procedure (LEEP): Involves surgical removal of abnormal areas from cervix using a thin heated wire). Successful in eradicating precancerous lesions in >90% of cases.
  • Cold knife conization: Removal of a cone shaped area from the cervix. Inpatient procedure reserved for cases not resolved with LEEP or cryotherapy. Has a cure rate of 90-94%
  • Follow up should be 6 monthly with either Pap smear or colposcopy.
  • If no abnormality noted follow up should be yearly.

INVASIVE CERVICAL CANCER

SYMPTOMS

-Irregular menstrual bleeding,

- post coital bleeding,

-postmenopausal bleeding,

-persistent foul smelling vaginal discharge.

-Late symptoms: Urinary frequency/urgency, Lap

Very Late: severe back pain, weight loss, reduced urinary output, fistulae, pedal edema, and breathlessness.

STAGING

FIGO (international federation of gynaecology and obstetrics).

  • Stage o: carcinoma in situ
  • Stage 1a: Microinvasive-diagnosed only by means of a microscope.
  • Stage 1b: clinically visible but confined to cervix
  • Stage 11a: Spread into the upper 2/3 of vagina.
  • Stage 11b: Spread into the parametrium
  • Stage 111a:Extension into the lower 1/3 of vagina
  • Stage 111b: Extension to the pelvic wall with ureter invasion
  • Stage 1V a: Extension into bladder or rectal mucosa
  • Stage IV b: Spread into distant organs

TREATMENT

SURGICAL:

Simple Hysterectomy: Surgical removal of the entire uterus including the cervix. Used for treatment of stage 1a.

Radical Hysterectomy: Involves removal of uterus, cervix, parametria, 2cm of upper vagina and nodal dissection. Preferred for those with invasive cancer of the cervix stage 1b-11a.

RADICAL TRACHELECTOMY: includes removal of parametria and upper vaginal in addition to the cervix. It’s a fertility preserving surgery for microinvasive stages.

CHEMOTHERAPY: It is not used as a primary mode of treatment but maybe concurrently used with surgery or radiation to treat bulky tumors. Cisplatin is the most commonly used drug.

RADIOTHERAPY

Mainly for cases with bulkier disease stage 11b-1Vb. Extensive lymph node involvement, those unable to tolerate GA and in palliative care to alleviate PVB/bone pain.

Divided in 2 broad groups

  1. Teletherapy: (External beam radiation therapy).
  2. Sessions are given 5 days a week for 5 weeks. In total 25 sessions. Each session lasts a few minutes. Aim is to shrink the central carcinoma and possible sites of regional metastasis
  1. Brachytherapy:
  2. The radiation sources are placed inside an applicator in the uterus and vaginal wall which provides high dose to the central tumor.

PALLIATIVE CARE

  1. Pain Management
    Non opiod: paracetamol 1g 4-6hrly, brufen 400mg 6hrly or aspirin 600mg 4hrly.
    Opiods for mild to moderate pain: codeine 30mg 4hrly.
    Opiods for severe pain: morphine liquid based. 2.5-5mg 4hrly.
    There is no standard dose for opiod drug. The right dose is the dose that relieves the patient’s pain.
    All opiods are given together with laxative to prevent constipation.
  2. Nursing care: frequent change of absorbent pads, sitz baths, changing linen frequently.M
  3. Psychosocial and spiritual support
  4. Palliative surgery
  5. Palliative radiation
  6. Nerve blocking procedure
  7. Surgical division of spinothalamic tract: cordotomy.

PROGNOSIS

Survival rate is expressed as the proportion of women surviving 5 years after receiving treatment.
Stage 1: >85%
Stage 2: 50%
Stage 3: 25%
Stage 4: 5%

FACTORS INFLUENCING PROGNOSIS
Clinical stage
Age: survival reduces with age
Lymph node status
General health: nutrition status, anaemia
Degree of immunesuppresion.