Gynaecological Cancer
Sophia Julian
Consultant Gynaecological Oncologist
UHCW
Jan 2015
Aims and Objectives
Warwick Medical School
MbChB Phase 2: Jan 2012
8.20 Gynaecological Cancer
By the end of Phase 2 students should be able to:
•
Recognise the presnting symptoms of common gynaecological neoplasia
both in terms of site specific symptoms and in terms of effects on adjacent
organs
•
Plan the initial diagnostic and investigative approaches available to confirm
clinical suspicions
•
Explain the result of a cervical cytology report including intraepithelial
neoplasia and its possible consequences
•
Discuss sensitively with patients the principles of management of
gynaecological malignancies
•
Discuss the scope for prevention of cervical cancer
Plan
• Overview of Gynaecological Malignancy
• Networks
•
•
•
•
Vulval and Vaginal cancers
Uterine cancer (Endometrial)
Ovarian cancer (inc Tubal and PPC)
Cervical cancer and screening
Leukaemia
Other Sites**
3196
34053
2.10%
22.10%
* Colorectum including anus (C18-C21)
Gynaecological Cancer in Context
** 4% of all female cases are registered without specification of the primary site
Overview
No of Cases
Deaths
%
10yr Survival
Uterine
2012
8475
2025
3%
78%
Ovarian
2012
7116
4271
2%
35%
Cervix
2011
3064
972
1%
63%
Vulva
2011
1203
405
<1%
Vagina
2011
256
111
<1%
• Age range 20’s to 90’s
• Psychosexual impact
• Impact on families / children
•
2000 NHS Cancer Plan
•
Concentrate care into site-specialist,
multi-disciplinary teams
•
NSSG Gynaecology
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–
–
–
–
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Developing guidelines
Implementing good practice
Co-ordinating expert clinical advice
Develop local strategy
Improve quality of care
Address inequalities in provision & access
Cancer Centres and Cancer Units
Vulval and Vaginal Cancers
• Very rare
• Elderly patients
• Usually SCC
– 50% caused by HPV
– 50% caused by chronic skin disease
• Surgery (anatomical considerations)
• Radiotherapy / Chemoradiotherapy
Vulval Cancer
Endometrial Cancer
Epidemiology
•
•
•
•
•
•
•
Commonest gynaecological cancer in UK
Incidence is rising
4th Commonest cancer in women
Rare before the age of 35
Peak age group 64 – 74
Declines after age 80
Commoner in western world
http://info.cancerresearchuk.org/cancerstats/types/uterus/incidence/
Endometrial Cancer: Pathology
Endometrial hyperplasia
Pre-malignant condition
Classification simple, complex, atypical
With atypical malignancy co-exists in 2550% of cases, and 20% will develop Ca
within 10 years.
Treat with progestagens / surgery
Endometrial carcinoma
TYPE 1 (80%): Endometrial Adenocarcinoma
Stage
AND
Grade 1,2,3
TYPE 2 (20%): Papillary Serous
Clear cell
Carcinosarcoma
Sarcoma
Extremely rare
Normal Endometrium
Endometrial Hyperplasia
Risk factors
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•
•
•
•
•
•
•
•
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Obesity (37% of cases caused by being too fat!)
Nulliparity
Early menarche
Late menopause
Unopposed oestrogen
Tamoxifen
Oestrogen producing tumours
Diabetes
PCOS
HNPCC
Early Presentation
• Pre-menopausal
– Abnormal vaginal bleeding
– Intermenstrual bleeding
– Irregular bleeding / periods
• Postmenopausal
– Postmenopausal Bleeding (PMB)
– 10% of women with PMB will have a malignancy
– Less commonly blood stained, watery or purulent
vaginal discharge
Diagnostics
• Endometrial sampling by Pipelle or (less
commonly) D&C
• Hysteroscopy: gold standard
• Transvaginal Ultrasound: useful for
investigation of PMB, use >5mm cut off for
endometrial thickness
Transvaginal USS
Pipellle Biopsy
Other Investigations
• Type 1 Cancers
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–
–
–
Metastasis rare at presentation
Intraperitoneal, lung, bone, brain
FBC, U&E, LFT and CXR
MRI only if suspicion of
deep myometrial invasion
• Type 2 Cancers
– Metastasis more likely
– CT Chest / Abdomen / Pelvis
– MR Pelvis
FIGO Staging 2009
Stage
1
2
3
4
Tumour
5 Year Survival
Limited to myometrium
80%
Cervical spread
60%
Uterine serosa
Ovaries / Tubes Vagina
Pelvic / Para-aortic Lymph Nodes
40%
Bladder / bowel involvement
Distant metastatsis
20%
Treatment
•
Conservative
•
Medical
– Progestatgens (oral or intrauterine/Mirena IUS)
– Primary Radiotherapy
•
Surgical
– Hysterectomy, BSO, peritoneal washings
– Laparoscopic / Open (TAH)
– Pelvic Lymph node dissection: no survival advantage (ASTEC)
•
Adjuvant Radiotherapy if high risk of recurrence
– Brachytherapy
– External beam
•
Advanced disease/inoperable disease/unfit for surgery
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–
–
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Chemotherapy
Radiotherapy
Hormones
Palliative Care
Ovarian Cancer
Epidemiology
• Second commonest gynae cancer in the UK
• Incidence is rising
• Lifetime risk 1:50
• Peak age 70-74 years, occurs predominantly in
5th, 6th and 7th decade
Pathology
Benign
Borderline
Malignant
Cell Line
Surface Epithelium
(EOC)
85 – 90%
Serous (50%)
Mucinous (10-15%)
Endometriod (10-15%)
Clear Cell (5%)
Brenner Tumours
Germ Cells
Stroma/Sex Cord
Dysgerminoma
Teratoma
Yolk Sac
Choriocarcinoma
Granulosa Call
Theca Cell
Sertoli-Leydig Cell
Fibroma
No pre-malignant stage
Spread: usually intra-peritoneal
Miscellaneous &
Metastatic
Primary Lymphomas
Metastases
Krukenberg Tumour
Pathology
Borderline
common
do not invade
Epithelial
Serous
Mucinous
Endometroid
Clear cell
common
common
uncommon
uncommon
benign and malignant
benign and malignant
usually malignant
usually highly malignant
Germ cell
Teratoma
Dysgerminoma
Yolk sac
Choriocarcinoma
common
rare
rare
rare
benign, very rarely malignant
secretes HCG
Malignant, secretes AFP
Highly malignant
rare
rare
rare
low grade, secrete oestrogen
Usually benign, secrete oestrogen
may secrete androgens
Stroma/sex Granulosa cell
cord
Theca cell
Sertoli-Leydig
*Primary Peritoneal Cancer (PPC), Fallopian tube Cancer
Ovarian Tumours
Benign Tumour
Malignant Tumour
EOC: Risk factors
Increase Risk:
Decrease Risk:
• Reproductive history
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Nulliparity
Infertility
Early menarche
Late menopause
• HRT
• ? Asbestos
• ? Talcum powder
• ? Smoking,diet, alcohol
COCP
• Pregnancy
• Breastfeeding
• Hysterectomy
• Oophorectomy
• Sterilisation
Genetic factors
• 5 - 10% of all cases of epithelial ovarian cancer
None
1-2%
One First degree relative
4-10%
Two First degree relatives
3-23%
Hereditary Ovarian cancer syndrome
BRCA1
50%
BRCA2
27%
HNPCC
12%
Presentation
• Non-specific symptoms
• Occasionally incidental finding
• 17% present with advanced disease
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•
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Abdominal swelling
Pain
Anorexia
N&V
Weight loss
Vaginal bleeding
Change in bowel habit
50-65%
50-60%
20%
20%
15%
15%
5%
Diagnosis and Investigation
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Pelvic examination
TVS
FBC, U&E, LFT
CA125
CXR
CT to assess peritoneal, omental and retroperitoneal
disease
• Radiologically (USS/CT) guided biopsy
• (Cytology of ascitic tap)
• Surgical exploration
• Histopathology
Tumour Marker: Ca125
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•
•
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Up in 80% of advanced EOCs
Increased in max. 50% of stage I disease
Poor specificity, especially premenopausal
Also increased with
– Ca pancreas, breast, colon, lung
– Menstruation, PID, Endometriosis
– Liver disease, ascites, pleural & pericardial
effusions
– Recent laparotomy
NICE Guidlines
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•
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April 2011
Controversial
Ca125 as initial screen if symptoms
USS if Ca125 abnormal
Look for other causes of raised Ca125 if
USS normal
Other Tumour Markers
• Can be useful in cases of disseminated disease
where the ovarian mass might not be the
primary cancer
• Ca19.9
• CEA
• Ca15.3
• Limited sensitivity and specificity!
Imaging
Staging (FIGO 2013)
Stage
Tumour
5 Year Survival
1
Limited to ovary / ovaries
90%
2
Spread to pelvic organs
60%
3
Spread to rest of peritoneal cavity
Omentum
Positive Lymph nodes
30%
4
Distant metastatsis
Liver parenchyma
Lung
5%
Overall 41%
Stage 3 Disease
Treatment
• Epithelial cancer
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–
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A combination of Surgery + chemotherapy
Staging laparotomy, TAH,BSO and debulking
Platinum (Carboplatin) and Taxane (paclitaxel)
In women of reproductive age, where the tumour is confined to
one ovary ophorectomy only may be considered
• Non-epithelial tumours: often occur in young women and
can be extremely chemo-sensitive (e.g. germ cell). Often
treated with combination of ‘conservative’ surgery and
chemo
• Recurrent disease: palliative chemotherapy
Cervical Carcinoma and Screening
Cervical Ca. Epidemiology
• Worldwide - in some areas commonest cancer in women
• UK 3rd commonest gynae cancer
• 80% of cervical cancer occurs in developing world
– 5% lifetime risk in some regions
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•
•
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Incidence declined by 40% with cervical screening
Bimodal age distribution (30s and 80s)
More common in low socio-economic groups
2/3 are squamous ca 15% are adenocarcinoma
http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/
Risk Factors
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Young age at first intercourse
Multiple sexual partners
Smoking
Long term use of COCP
Immunosuppression/HIV
» » HPV (Human papilloma virus): STI
HPV
• About 100 types
• 40 types target genital tract
• Oncogenic (high-risk) types
– 16, 18, 31, 33, 34, 35, 39,
45, 51, 52, 56, 58, 59, 66, 68
• Low-risk HPV types
– 6, 11, 42, 43, 44
Human Papilloma Virus (1)
• HPV (esp subtypes 16 & 18): produce proteins (E6&7) which
suppress the products of ‘p53’ tumour suppressor gene in
keratinocytes
• Most women will be infected at some time
• HPV infection is common in late teens and early twenties
• Infection lasts on average 8 months
• Prevalence 5% by age 50
– Immunological clearance of virus
– Reduced opportunities for re-infection
Human Papilloma Virus (2)
• HPV is an accepted necessary (but not
sufficient) cause of cervical cancer
• Cervical cancer could be viewed as a rare
complication of a common infection
• A vaccine might prevent cervical
carcinoma
– Biggest implication is in developing nations
Cervical Intraepithelial Neoplasia
(CIN)
• Pre-malignant
condition
• Occurs at the TZ
• Asymptomatic
Stratified Squamous Epithelium
CIN
Histological Diagnosis!!
CIN
Natural History
• HPV
– Asymptomatic
– Can be cleared or persist or cause CIN
• CIN
– Asymptomatic
– Can regress, persist or progress to cancer
– Best Estimates
• 60% CIN1 regress spontaneously
• 30% of CIN3 progress to invasion over 5-10 years
Regression, Persistence and
Progression
Progression
Regression Persistence
to CIN III
Invasion
CIN I
57%
32%
11%
1%
CIN II
43%
35%
22%
5%
CIN III
32%
<56%
..
>12%
Ostor AG. Int J Gynecol Pathol 1993; 12(2): 186-192.
Cervical Cytology
• Cells collected from cervix and morphology
examined
• Pap Smear
• Liquid based cytology
• Classification / reporting
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Normal
Inadequate
Borderline
Mild Dyskaryosis
Moderate Dyskaryosis
Severe Dyskaryosis
Possible Invasion
Cervical Smear
Smear Frequency
• First invitation age 25
• 3 yearly from 25 to 50
• 5 yearly from 50 – 65
• After 65 selected patients only
http://www.bsccp.org.uk/docs/public/pdf/nhscsp20.pdf
Referral to Hospital
HPV Triage
• Inadequate smear on three occasions
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Borderline smear + for HR-HPV
Mild dyskaryosis + for HR-HPV
Moderate dyskaryosis
Severe dyskaryosis
• Abnormal glandular cells present
• Suggestion of Invasive disease
Colposcopy
• Low-power binocular
microscopy of cervix
• To look for features
suggestive of CIN or
invasion
• abnormal vascular
pattern (mosaicism,
punctation)
• abnormal staining of the
tissue (aceto-white,
brown iodine)
Normal Cervix
Squamocolumnar junction
Acetowhite
Acetowhite, Mosaic, Punctation
Iodine negative
Invasive carcinoma
Treatment for CIN
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See-and-treat concept vs. biopsy and treat
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Destructive: cryocautery, diathermy, laser
vaporisation
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Excisional: LLETZ (large loop excision of the
transformation zone), cold knife cone
•
Following colposcopy, follow up should be
after 6 months and then annually for 10 years
(remain at increased risk)
LLETZ
• 1 treatment 95%
success
• Most failures evident
in first year
Follow up After Treatment
• CIN 1: Smears at 6, 12, 24 months
• CIN 2/3: Smears at 6, 12, 24 months then
annually for 8 years
• HPV Test of Cure for all treated women
– Local protocols
– Smear and HPV test at 6 months
– Discharge to normal recall if HPV negative
Summary
Smear
Colposcopy
Biopsy
Cytology: Detects dyskaryosis
mild/moderate/severe
Gives colposcopy opinion
and directs biopsy / perform
treatment
Histological diagnosis
of CIN 1/2/3/Invasion
Cervical Ca. Presentation
1. PCB
2. PMB
3. IMB
4. Blood stained vaginal discharge
In very advanced disease:
Fistulae, renal failure, nerve root pain, lower limb
oedema
50% with cervical ca have never had a smear
Staging: Clinical
1
Confined to cervix (90%)
A Microinvasive (depth<5 mm/width<7mm)
B Clinical lesion
2
Beyond cervix but not pelvic side wall or lower 1/3 of vagina (60%)
A Upper 1/3 Vagina
B Parametrium
3
Pelvic spread, reaches side wall or lower 1/3 of vagina (30%)
A Lower 1/3 of vagina, hydronephrosis
B Extends to pelvic side wall, hydronephrosis
4
Distant spread (10-20%)
A Invades adjacent organs (bladder/bowel)
B Distant sites
MRI
Treatment
1. Microinvasive carcinoma: can be more conservative. If fertility is an
issue, then cone biopsy can be used. Once family is complete, hysterectomy is
appropriate.
2. Clinical Lesions (1b - 2a): Wertheim’s radical hysterectomy or
chemoradiotherapy (survival same)
3. Clinical lesions beyond stage 2a: Chemoradiotherapy
4. Postoperative radiotherapy: with lymph node involvement
5. Recurrent disease: Radiotherapy, chemotherapy, exenteration,
palliative care
Ideally patients only receive ONE treatment modality to reduce morbidity of treatment
Surgery OR chemoradiotherpy NOT BOTH
Complications
Surgery:
• Infection
• VTE
• Haemorrhage
• Vesicovagina fistula
• Bladder dysfunction
• Lymphocyst formation
• Short vagina
Radiotherapy:
• Vaginal dryness
• Vaginal stenosis
• Radiation cystitis
• Radiation proctitis
• Loss of ovarian function
Pelvic lymphadenectomy
Radical Trachelectomy
Pelvic Exenteration
Vaccination
• Gardasil: 6,11,16,18
• Cervarix:16 & 18
• NHS Programme
• 3 im injections over 6
months
• Ideally prior to SI
• 5 years protection
• Still need smears (HPV
31, 45 & others)
Questions?
Summary
Further Information
• For up to date information about cancer
http://info.cancerresearchuk.org/cancerstats/?a=
5441
• For cervical cancer, screening and vaccination
http://www.bsccp.org.uk