1. Treatment for Cervical Cancer
Dr Sai Daayana
Clinical Lecturer in Gynaecology Oncology
St Mary’s Hospital, Manchester

2. Malignant Transformation
HPV types 16, 18, 31, 33 & 45 are ‘high risk’
Most HPV infections are transient & disappear without ever causing dysplasia
Persistent high risk HPV infection is linked to cervical carcinogenesis
Only 30% CIN 3 lesions progress to cervical squamous cell cancer, if left untreated, over years
Unable to distinguish lesion that will regress from one that will progress
Therefore need to treat all high grade CIN

3. CERVICAL INTRAEPITHELAIL NEOPLASIA
Abnormalities in the surface cells of the cervix that may become cancerous. CIN is not a cancer. There are 3 grades of CIN -
Histological grade
Cytology
Description
CIN 1
Low grade intraepithelial lesion (LSIL)
Mild dysplasia confined to the basal 1/3 of the epithelium
CIN 2
High grade intraepithelial lesion (HSIL)
Moderate dysplasia confined to the basal 2/3 of the epithelium
CIN 3
Severe dysplasia spanning more than 2/3 of the epithelium

4. Cervical Glandular Intraepithelial Neoplasia
Pre-invasive disease of the endocervix (pre-cursor of adenocarcinoma of the cervix)
CGIN graded 1-3 similar to CIN
May be detected by smear showing ‘abnormal glandular cells’
More commonly detected at colposcopy where there is co-existing CIN
Or in the LLETZ or cone biopsy specimen performed for a high grade CIN lesion

5. HISTOLOGY
LSIL
HSIL
HSIL

6. Colposcopic pictures of CIN

8. Cervical Cancer (1) Epidemiology
Second most common cause of cancer related death in women world wide
Median age at diagnosis 52 years
Aetiology
Persistent infection with high risk HPV subtypes (HPV 16, 18, 31, 33 & 45 linked to 85% cancer cervix)
Immunosuppression
Smoking
Sexual promiscuity, early age at first coitus, multiple partners
Use of combined oral contraceptive pill

9. Cervical Cancer (2) Clinical features
Post coital, intermenstrual or persistent vaginal bleeding
Friable, papillary or polypoid mass
Hard, bulky, nodular mass which eventually ulcerates
Pathology
Squamous Cell Carcinoma -70%
Adenocarcinoma
Adenosquamous carcinoma - rare, poor prognosis

10. Cervical Cancer (3): Squamous Cell Carcinoma
Invades locally into uterine body, vagina, parametrial tissues, bladder & rectum
Lymph node spread to pelvic, iliac & aortic nodes occurs early
Metastasis to liver, lungs & bone by blood occurs late
5 year survival rate for Stage I disease is 85%, falling to 50-75% for Stage II+

11. Cervical Cancer (4): Adenocarcinoma
Clear Cell type occurs in young girls exposed prenatally to DES (diethylstilbesterol)
Increasing in incidence but relatively uncommon
Associated with especially HPV 18 infection
Grows in endocervix & is commonly well differentiated
Spreads upwards into the myometrium & outwards into the pelvis
5 year cure rate is relatively poor

12. Squamous cell carcinoma of the cervix

13. FIGO Staging of Cervical Cancer
I Carcinoma strictly confined to cervix
IA Diagnosed only by microscopy with deepest inv 5mm and largest ext 7mm
1A1 Stromal inv of  3mm in depth and extension of  7 mm
1A2 Stromal inv of 3-5mm with extension of not 7mm
IB Clinically visible lesions limited to cervix or preclinical cancers IA
IB1 Clinically visible lesion 4cm in greatest dimension
IB2 Clinically visible lesion 4cm in greatest dimension
II Carcinoma invades beyond the uterus, but not to pelvic wall or to the lower third of the vagina
IIA without parametrial invasion
IIA1 Clinically visible lesion  4cm in greatest dimension
IIA2 Clinically visible lesion  4 cm in greatest dimension
IIB with obvious parametrial invasion
IIIA Extends to lower third of vagina
IIIB Extension to pelvic side-wall and/or hydronephrosis or non-functioning kidney
IV Biopsy proven carcinoma extended beyond true pelvis/mucosa of bladder or rectum

14. Stage I Cervical Cancer

15. Treatment for CIN2/3, Stage Ia Cervical Carcinoma –
LLETZ (large loop excision of the transformation zone)
Usually performed in the colposcopy clinic under local anaesthesia
Cone biopsy
Performed in the operating theatre under general anaesthesia

16. Stage IB Cervical Cancer

17. Stage IIA Cervical Cancer

18. Treatment for Stage Ib, IIa Cervical Carcinoma – Trachelectomy, performed open, laparoscopic or vaginal

19. TRACHELECTOMY

20. Cerclage placed after trachelectomy

21. Radical hysterectomy performed open or laparoscopic
Complete removal of uterus, cervix, upper vagina and parametrium. Pelvic lymph nodes, fallopian tubes and ovaries are also usually removed

22. Total vs. Radical hysterectomy

23. Stage III Cervical cancer

24. Radiotherapy treatment for Cervical cancer
Can be administered externally, internally or both
External beam radiotherapy – beams are directed at the body in the radiotherapy department, usually once a day, five days a week for four weeks
Internal radiotherapy – in pt treatment - radioactive source is put into the vagina (if uterus removed) or into the uterus for 14 – 24 hours usually. Treatment may be repeated a week later. Usually given 1-2 weeks following external beam radiotherapy
Side-effects from pelvic radiotherapy
Diarrhoea, Irritable bladder
Nausea, Perineal soreness and redness
Long-term side effects
Menopause, Vaginal stenosis
Long-term bladder / bowel side-effects

25. Intracavity Radiotherapy

26. External Beam Radiotherapy

27. Radiotherapy burns to the perineum

28. Stage IVA Cervical cancer

29. Stage IVB Cervical cancer

30. Chemotherapy for Cervical cancer
In cervical cancer most commonly cisplatin chemotherapy may be given –intravenously, once a week or once every 3-4 weeks for several cycles
With radiotherapy – this is chemoradiation
If the cancer has spread – to control it and reduce symptoms
Before surgery or radiotherapy to shrink the size of a tumour
Side-effects of cisplatin
Drop in blood cell count, increased risk of infection, bleeding, anaemia
Nephrotoxicity, Neurotoxicity, Ototoxicity
Fatigue, Nausea and vomiting
Electrolyte disturbance

31. Intravenous chemotherapy administration

32. Intravenous chemotherapy administration

33. 5-year Survival Rates for Cervical Cancer
The numbers below come from the National Cancer Data Base, and are based on people diagnosed between 2000 and 2002
Stage 5-Year Survival Rate
0 93%
IA 93%
IB 80%
IIA 63%
IIB 58%
IIIA 35%
IIIB 32%
IVA 16%
IVB 15%

35. TREATMENT OF CERVICAL CANCER
Treatment depends on the stage of the disease
Treatment options:
LLETZ
Cone biopsy
Total hysterectomy
Radical trachelectomy
Radical abdominal hysterectomy
External beam &
intracavity radiotherapy
Chemotherapy
Stage IA
Stage IB, IIA
Stage IIB or more, high grade disease with other stages