1. Gynaecological Cancer
Sophia Julian
Consultant Gynaecological Oncologist
UHCW
Jan 2015

2. Aims and Objectives

3. Warwick Medical School MbChB Phase 2: Jan 2012 8
Warwick Medical School MbChB Phase 2: Jan 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

4. Plan Overview of Gynaecological Malignancy Networks
Vulval and Vaginal cancers
Uterine cancer (Endometrial)
Ovarian cancer (inc Tubal and PPC)
Cervical cancer and screening

5. Gynaecological Cancer in Context

6. Overview Age range 20’s to 90’s Psychosexual impact
No of Cases
Deaths %
10yr Survival
Uterine
2012
8475
2025 3%
78%
Ovarian
7116
4271 2%
35%
Cervix
2011
3064
972 1%
63%
Vulva
1203
405
<1%
Vagina
256
111
Age range 20’s to 90’s
Psychosexual impact
Impact on families / children

7. Concentrate care into site-specialist, multi-disciplinary teams
2000 NHS Cancer Plan
Concentrate care into site-specialist,
multi-disciplinary teams
NSSG Gynaecology
Developing guidelines
Implementing good practice
Co-ordinating expert clinical advice
Develop local strategy
Improve quality of care
Address inequalities in provision & access

8. Cancer Centres and Cancer Units

9. 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

10. Vulval Cancer

11. Endometrial Cancer

12. 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

13. Endometrial Cancer: Pathology
Endometrial hyperplasia
Pre-malignant condition
Classification simple, complex, atypical
With atypical malignancy co-exists in 25-50% of cases, and 20% will develop Ca within 10 years.
Treat with progestagens / surgery
Endometrial carcinoma
Stage
AND
Grade 1,2,3
TYPE 1 (80%): Endometrial Adenocarcinoma
TYPE 2 (20%): Papillary Serous
Clear cell
Carcinosarcoma
Sarcoma
Extremely rare

14. Normal Endometrium

15. Endometrial Hyperplasia

16. Risk factors Obesity (37% of cases caused by being too fat!)
Nulliparity
Early menarche
Late menopause
Unopposed oestrogen
Tamoxifen
Oestrogen producing tumours
Diabetes
PCOS
HNPCC

17. Early Presentation Pre-menopausal Postmenopausal
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

18. 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

19. Transvaginal USS

20. Pipellle Biopsy

21. Other Investigations Type 1 Cancers Type 2 Cancers
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

22. FIGO Staging 2009 Stage Tumour 5 Year Survival Limited to myometrium1
Limited to myometrium
80% 2
Cervical spread
60% 3
Uterine serosa
Ovaries / Tubes Vagina
Pelvic / Para-aortic Lymph Nodes
40% 4
Bladder / bowel involvement
Distant metastatsis
20%

23. Treatment Conservative Medical Surgical
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
Chemotherapy
Radiotherapy
Hormones
Palliative Care

24. Ovarian Cancer

25. Epidemiology Second commonest gynae cancer in the UK
Incidence is rising
Lifetime risk 1:50
Peak age years, occurs predominantly in 5th, 6th and 7th decade

26. Pathology Benign Borderline Malignant No pre-malignant stage
Spread: usually intra-peritoneal

27. Pathology *Primary Peritoneal Cancer (PPC), Fallopian tube Cancer
Borderline
common
do not invade
Epithelial
Serous
Mucinous
Endometroid
Clear cell
uncommon
benign and malignant
usually malignant
usually highly malignant
Germ cell
Teratoma
Dysgerminoma
Yolk sac
Choriocarcinoma
rare
benign, very rarely malignant
secretes HCG
Malignant, secretes AFP
Highly malignant
Stroma/sex cord
Granulosa cell
Theca cell
Sertoli-Leydig
low grade, secrete oestrogen
Usually benign, secrete oestrogen
may secrete androgens
*Primary Peritoneal Cancer (PPC), Fallopian tube Cancer

28. Ovarian Tumours

29. Benign Tumour

30. Malignant Tumour

31. EOC: Risk factors Increase Risk: Reproductive history HRT ? Asbestos
Nulliparity
Infertility
Early menarche
Late menopause
HRT
? Asbestos
? Talcum powder
? Smoking,diet, alcohol
Decrease Risk:
COCP
Pregnancy
Breastfeeding
Hysterectomy
Oophorectomy
Sterilisation

32. 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%

33. Presentation Non-specific symptoms Occasionally incidental finding
17% present with advanced disease
Abdominal swelling 50-65%
Pain %
Anorexia 20%
N&V 20%
Weight loss 15%
Vaginal bleeding 15%
Change in bowel habit 5%

34. Diagnosis and Investigation
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

35. Tumour Marker: Ca125 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

36. NICE Guidlines April 2011 Controversial
Ca125 as initial screen if symptoms
USS if Ca125 abnormal
Look for other causes of raised Ca125 if USS normal

37. 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!

38. Imaging

39. Staging (FIGO 2013) Stage Tumour 5 Year Survival
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%

40. Stage 3 Disease

41. Treatment Epithelial cancer
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

42. Cervical Carcinoma and Screening

43. 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
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

44. Risk Factors Young age at first intercourse Multiple sexual partners
Smoking
Long term use of COCP
Immunosuppression/HIV
» » HPV (Human papilloma virus): STI

45. 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

46. 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

47. 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

48. Cervical Intraepithelial Neoplasia (CIN)
Pre-malignant condition
Occurs at the TZ
Asymptomatic

49. Stratified Squamous Epithelium

50. Histological Diagnosis!!
CIN
Histological Diagnosis!!

51. CIN

52. Natural History HPV CIN Asymptomatic
Can be cleared or persist or cause CIN
CIN
Can regress, persist or progress to cancer
Best Estimates
60% CIN1 regress spontaneously
30% of CIN3 progress to invasion over 5-10 years

53. Regression, Persistence and Progression
Progression to CIN III
Invasion
CIN I
57%
32%
11% 1%
CIN II
43%
35%
22% 5%
CIN III
<56% ..
>12%
Ostor (1993) reviewed the literature on the natural regression, persistence and progression of pre-cancerous cervical lesions and calculated that the approximate likelihood of regression of CIN I was 57%, persistence 32%, progression to CIN III 11% and progression to invasion 1%. The corresponding figures for CIN II were 43%, 35%, 22% and 5% respectively. And the likelihood of CIN 3 regressing was 32% and progressing to invasion greater than 12%
These estimates vary depending on which paper is read; however, the overall message is that the more advanced the pre-cancerous lesions are, the more likely they are to progress to invasive cervical cancer
The mechanisms that affect progression/regression are not known at present
Ostor AG. Int J Gynecol Pathol 1993; 12(2):

54. Cervical Cytology Cells collected from cervix and morphology examined
Pap Smear
Liquid based cytology
Classification / reporting
Normal
Inadequate
Borderline
Mild Dyskaryosis
Moderate Dyskaryosis
Severe Dyskaryosis
Possible Invasion

55. Cervical Smear

56. Smear Frequency First invitation age 25 3 yearly from 25 to 50
After 65 selected patients only

57. Referral to Hospital HPV Triage
Inadequate smear on three occasions
Borderline smear + for HR-HPV
Mild dyskaryosis + for HR-HPV
Moderate dyskaryosis
Severe dyskaryosis
Abnormal glandular cells present
Suggestion of Invasive disease

58. 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)

59. Normal Cervix

60. Squamocolumnar junction

61. Acetowhite

62. Acetowhite, Mosaic, Punctation

63. Iodine negative

64. Invasive carcinoma

65. Treatment for CIN See-and-treat concept vs. biopsy and treat
Destructive: cryocautery, diathermy, laser vaporisation
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)

66. LLETZ
1 treatment 95% success
Most failures evident in first year

67. 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

68. Summary Smear Colposcopy Biopsy Cytology: Detects dyskaryosis
mild/moderate/severe
Colposcopy
Gives colposcopy opinion
and directs biopsy / perform
treatment
Biopsy
Histological diagnosis
of CIN 1/2/3/Invasion

69. Cervical Ca. Presentation
PCB
PMB
IMB
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

70. 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

71. MRI

72. Surgery OR chemoradiotherpy NOT BOTH
Treatment
Microinvasive carcinoma: can be more conservative. If fertility is an issue, then cone biopsy can be used. Once family is complete, hysterectomy is appropriate.
Clinical Lesions (1b - 2a): Wertheim’s radical hysterectomy or chemoradiotherapy (survival same)
Clinical lesions beyond stage 2a: Chemoradiotherapy
Postoperative radiotherapy: with lymph node involvement
Recurrent disease: Radiotherapy, chemotherapy, exenteration, palliative care
Ideally patients only receive ONE treatment modality to reduce morbidity of treatment
Surgery OR chemoradiotherpy NOT BOTH

73. 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

74. Pelvic lymphadenectomy

75. Radical Trachelectomy

76. Pelvic Exenteration

77. 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)

78. Questions?

79. Summary

80. Further Information For up to date information about cancer
For cervical cancer, screening and vaccination