Ca cervix

KKB EDWARD MBChB-V

What?

Every 2 minutes one woman dies from cervical cancer in this world

Cervical Cancer: A Global Problem

~500,000 new cases/year worldwide ~270,000 deaths/year worldwide

Rate per 100,000 population (all ages) Ferlay J et al. Globocan 2002. IARC 2004

Cancer incidence among women in Uganda

Dysplasia and HPV

Infection with high risk strains
16, 18, 31, 33, 39, 45, 51

Spectrum of HPV;
Condyloma Acuminata Cervical Dysplasia Cervical Cancer

HPV
Risk Factors;
Early onset of intercourse. Multiple sexual partners. Sex partners who have had multiple partners. Cigarette smoking (increase risk X 4). Immunosuppression.

Source: Schiffman M,et al.,2005

The natural history of cervical cancer

A wake-up call!
Cervical cancer is a rare complication of a common STI. Any STD can be prevented and so

Cancer of the cervix can also be prevented!

Alleviate suffering from cancer cervix

The 4 pillars

Prevention of HPV infection

Screening for dysplasias

Early diagnosis and treatment

Palliative care

Alternatives for cervical cancer screening

Visual inspection with acetic acid (VIA) Visual inspection with Lugols iodine (VILI)

Conventional pap

HPV DNA testing

Pap Smear
Sample cervical cells from transformation zone.
junction of endocervix and ectocervix

Send to cytology for review of cells. Classified according to Bethesda System.

Qualities of an adquate pap smear specimen

The patient and the specimen are prominently identified Pertinent clinical history is available The sample is technically interpretable (not more than 50%of the cells are obscured by inflammation, debris, or blood) There is evidence that the cervical transformation zone has been sampled.

Bethesda Classification (2001)

Squamous Cell
Atypical squamous cells (ASC)
Undetermined Significance (ASC-US) Not excluding High Grade (ASC-H)

Low Grade Squamous Intraepithelial lesion (LSIL) High Grade Squamous Intraepithelial lesion (HSIL) Squamous Cell Carcinoma

Glandular Cell
Atypical Glandular cells (AG)
Undetermined Significance (AG-US) Favors Neoplasm

Adenocarinoma In Situ (AIS) Adenocarcinoma

Management of Cervical Dysplasia

Squamous Cells;
ASC-US
Repeat pap at 6-12 months, HPV test

LSIL
In adolescents, just repeat Pap e very6-12 months. Non-adolescent, HPV test, Colposcopy & Cervical Biopsy. If LSIL, repeat Pap every 6-12 months. If HSIL, treat with excision or ablation.

HSIL
HPV test, Colposcopy, Cx Bx, & Endocervical Bx. If HSIL present, excision (LEEP) or ablation (cryotherapy).

Treatment of CIN
Ablative techniques
Cryotherapy Laser ablation

Excision procedures
Cold knife conization Laser cone excision Loop electrosurgical excision procedure (LEEP)

ACOG recommendations- Nov. 20th 2009

Screening should begin at age 21 years Screen every 2yrs for women aged 21 to 29 years. The interval be extended to every 3 years for women at least aged 30 years who have
had 3 consecutive negative tests no history of CIN 2 or CIN 3 no HIV infection No other immunocompromised state

ACOG recommendations
Discontinue screening in women who have had a total hysterectomy for benign conditions and who have no history of high-grade CIN.

ACOG recommendations- level B evidence

Sexually active women younger than 21 years should be counselled and tested for STIs and should be counselled regarding safe sex and contraception. Discontinue screening by 65- 70 years in women who have had 3 or more consecutive negative cytology test results and no abnormal test results in the past 10 years Women previously treated for CIN 2, CIN 3, or cancer should continue screening annually for at least 20 years.

Molecular events leading to dysplasia

Oncogenic HPV types intergrate into human genom HPVs early replication proteins E1 & E2 enable the virus to replicate in cervical cells Late proteins E6 & E7 will lead to transformation of normal cells into abnormal cells

Molecular events
E7 binds to retinoblastoma tumor suppressor protein E6 binds to p53 tumor suppressor protein These bindings lead to degradation of the suppressor proteins Then cell cycle deregulation and inhibition of apoptosis

Pathogenesis
Early stromal involvement 1-2 cm below the basement membrane is a localised process. Penetration beyond this carries increased risk of lymphatic and vascular involvement. Spread.
Direct. Lymphatic. Haematogenous

Lymphatic involvement regional nodes (parametrial, internal iliac (hypogastric and obturator) external iliac).
Clinically limited to cervix -15-26%

pathogenesis ctd.
Direct spread to the parametrium, if not treated compresses the ureters uraemia. The liver is the commonest site for haematogenous spread, but the lungs, brain, bones, adrenal glands, spleen and pancreas may be involved.

Histopathology.
Squamous cell carcinoma
Large cell, keratinizing squamous cell carcinoma Large cell, non-keratinizing squamous cell carcinoma Verrucous carcinoma Small cell carcinoma

Adenosquamous Adenoid cystic Lymphoepithelioma-like carcinoma Adenocarcinoma

Endocervical (mucinous) type ??Intestinal type Endometrioid type Clear cell type Serous type

Cervical Cancer
Signs & Symptoms;
Abnormal Vaginal Bleeding Postcoital Bleeding Vaginal Discharge (watery, mucoid, purulent, malodorous). Pelvic pain & low back pain. Bowel or urinary symptoms.

Diagnosis is mainly clinical

Palpation & inspection of the primary tumour. Palpation of groin & supraclavicular nodes. Colposcopy. Endocervical curettage. Conization. Hysteroscopy. Cystoscopy. Proctoscopy. IVP. Radiologic exam of lungs & skeleton.

Investigations continued
Preoperative evaluation
Full hemogram + ESR Renal functional tests Liver functional tests +/- ECG and cardiac echo.

Staging of Cervical Cancer (FIGO)

0 Carcinoma in situ. I Cervix carcinoma confined to uterus
IA Microscopic lesions &Stromal invasion with maximum depth of 5mm and width of 7mm
IA1 Invasion of not more than 3mm depth IA2 invasion of more than 3mm depth

IB macroscopic lesions and confined to the cervix

IB1 lesionsno greater than 4cm in size IB2 lesions greater than 4cm in size

Staging
II Cervix carcinoma invades beyond uterus but not to pelvic wall, it involves the vagina but not to the lower third
IIA No obvious parametrial involvement IIB obvious parametrial involvement

III Tumor extends to pelvic wall and/or involves the lower third of vagina, and/or causes hydronephrosis or nonfunctioning kidney.
IIIA no extension to pelvic walls but lower third of vagina IIIB extension to pelvic walls or hydronephrosis or nonfunctioning kidneys

Staging
IV Tumor extends beyond true pelvis or has involved bladder or rectum
IVA growth to adjacent pelvic organs IVB spread to distand organs

TREATMENT
RADIOTHERAPY; can be used for all stages of CACX SURGICAL CHEMOTHERAPY SUPPORTIVE

FACTORS AFFECTING CHOICE OF TREATMENT

Stage of the disease and the histological type Lymphovasular space involvement General condition of the patient; obesity, underlying medical conditions Reproductive goal of the patient Expertise and technology Patients decision and enthusiasm to resume normal activity

Piver Rutledge classification of hysterectomy

Type I: Extrafascial dissection of cervix and removal of the whole cervix Type II: Above+
uterine artery cut at crossover with ureter Uterosacrals cut midway attachment to sacrum Cardinal cut midway to attachment to pelvic wall Upper third of vagina

Type III: Dissect out the uterine arteries, uterosacrals, cardinals and upper of vagina Type IV: Dissect ureter from ligaments and upper of vagina Type V: Part of bladder and distal ureter are removed

Surgery per stage

Stage 1AI Conisation or type 1 hysterectomy Stage 1A2 type 2 hysterectomy Stage 1B and IIA<4cm type 3 hysterectomy

Treatment of Cervical Cancer

Early Stage (I II)
Radical Hysterectomy plus pelvic/paraaortic lymphadenectomy with or without adjuvant chemoradiotherapy. Radiation Therapy.

**Depends on age, childbearing, disease stage, comorbidities, patient & physician preference.

Treatment of Cervical Cancer

Locally Advanced Disease (II IV)
Primary Radiation Therapy with concomitant chemotherapy.

Cervical Cancer Follow Up

Clinical evaluation every three months for one year, every four months for one year, every six months for three years and then annually.
Annual chest x-ray.

Other radiographic images (CT, PET scan), as clinically indicated.

CACX in Pregnancy
In general CACX has no effect on Pregnancy Cervix is best not biopsed in first trimester because the risk of a spontaneous miscarriage is about 20% Cone biopsy only done if suspected invasive carcinoma Rx is the same except Dx is after viability, its delayed until 32 to 36 weeks .caesarean (classical) hysterectomy

Advantages OF RADICAL SURGERY

Ovarian function is retained Complications are more immediate and short term Avoids vaginal atrophy and fibrosis in young women, less dyspareunia Possible psychological advantage

Disadvantages OF RADICAL SURGERY

Up to 5% long term bladder dysfunction. Up to 8% long term complications to bladder and bowel Acute complications of surgery; anesthetic, bleeding ,tissue injury, DVT, MI

PROGNOSIS
Most early cancers are cured Most advanced cancers are not. If CACX is destined to recur, 85% will do so in the first two years after treatment

PROGNOSIS .
If no recurrence by five years then it is unlikely to happen FIVE YEAR SURVIVAL RATES OF CACX stage 1..80% stage 2..65% stage 3..30% stage 415%

Factors affecting prognosis

Clinical staging Histological characteristics Underlying medical conditions Adherence to Rx and Follow up

Prevention of ca cervix
There are 3 main strategies of preventing Cacx: Primary prevention
Prevent HPV infection
Behavior change HPV vaccination
CERVARIX(TM); HPV 16/18 GARDASIL; HPV 6/11/16/18

Prevention
Secondary prevention
Screen for and treat precancerous lesions
Pap smear VIA/ VILI HPV DNA tests

Government involvement
Mass education and sensitization Capacity building among staff Capacity building in the facilities and infrastructure.