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

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 10-15 years Unable to distinguish lesion that will regress from one that will progress Therefore need to treat all high grade CIN

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

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

HISTOLOGY LSIL HSIL HSIL

Colposcopic pictures of CIN

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

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

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+

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

Squamous cell carcinoma of the cervix

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

Stage I Cervical Cancer

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

Stage IB Cervical Cancer

Stage IIA Cervical Cancer

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

TRACHELECTOMY

Cerclage placed after trachelectomy

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

Total vs. Radical hysterectomy

Stage III Cervical cancer

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

Intracavity Radiotherapy

External Beam Radiotherapy

Radiotherapy burns to the perineum

Stage IVA Cervical cancer

Stage IVB Cervical cancer

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

Intravenous chemotherapy administration

Intravenous chemotherapy administration

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%

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