This document discusses several pre-malignant gynaecological conditions including endometrial hyperplasia, cervical pre-invasive disease, and vulval intraepithelial neoplasia. It covers the epidemiology, risk factors, clinical presentation, diagnosis, classification, and treatment options for each condition. Endometrial hyperplasia can progress to endometrial cancer if left untreated, and treatment options include progesterone, hysterectomy, or endometrial ablation depending on severity. Cervical pre-invasive lesions are usually caused by HPV infection and may regress on their own, but higher grades have a risk of progressing to invasive cervical cancer without treatment. Screening and treatment modalities aim to identify and treat higher

1. Pre-malignant
Gynaecological
Conditions
Dr. Indunil Piyadigama

2. Endometrial
hyperplasia
• Irregular proliferation of the
endometrial glands with an
increased gland to stromal ratio
(more than 1:1)
• Lesions that mimic EH
• Disordered proliferation
• Secretory endometrium
• Benign polyps

3. Epidemiology
Rare in < 30yrs
Peak at 50-54
(common within
1st five years of
menopause)
Precursor of type 1
endometrial
cancer
3 times as
common as the
endometrial
cancer

4. Risk factors
Increased endogenous oestrogen
• Anovulation
• Obesity
• Diabetes
• PCOS
• Granulosa cell tumours
Exogenous oestrogen
• HRT - Cyclical use – Endometrial hyperplasia in 0.7%
• Tamoxifen
• Risk of hyperplasia 2-3 times higher than general population.
Currently restricted for 5 years use only
• Pretreatment screening, prophylactic hysterectomy or
endometrial sampling at a low threshold are suggested
interventions.
• Aromatase inhibitors – No increase in risk of cancer
Immunosuppression
Infection

5. Current classification -
WHO 2014
Hyperplasia
without
atypia
Atypical
hyperplasia

7. Risk of cancer
• Without atypia
• 5% risk of carcinoma over 20 years
• Majority (80%) regress without treatment
• Atypical hyperplasia
• Concurrent carcinomas can occur – 43%
• Progression to CA is 30% in 20 years

8. Clinical presentation
• AUB – 15% are diagnosed endometrial hyperplasia
• Intermenstrual bleeding
• Post menopausal bleeding
• Small number can be asymptomatic

9. Diagnosis
TVS
• In premenopausal is restricted to finding structural causes
• But for PCOS with absent withdrawal bleeding or AUB ET is
recommended
• <7mm unlikely to have endometrial hyperplasia

10. Pipelle biopsy
Despite negative biopsy 2% of women still can have endometrial
hyperplasia
Sensitivity
Premenopausal 80% Postmenopausal 75%

11. D&C
• Inpatient
• Up to 10% of endometrial pathologies missed

12. Hysteroscopy and biopsy
• Indications
• When EB fails
• Persistent AUB
• If intrauterine structural anomalies or
polyps suspected – Focal endometrial
pathology is seen in about 10% of
population
• Better at detecting rather than
excluding endometrial pathology
• 98% sensitive for hyperplasia

13. Treatment - Hyperplasia without atypia
Risk factor modification
• Weight
• Exogenous hormones

14. Progesterone
Indications
•Fail to regress following observation
•Symptomatic women
Type
•Continuous oral progesterone – MPA 10-20mg/day, NET 10-15mg/day
•LNG- IUS
Action
•Antimitotic on endometrial cells
•Modulating growth stimulatory signals of E2
•Reduces oestrogen secretion by HPO axis
•Reduces receptors
•Increases metabolism of E2
Higher disease regression rate (95%) compared to observation
alone (80%)
6 months use better than 3 months

15. Follow up
• EB with a minimum of 6 months treatment - 2 biopsies negative
shows cure and discharge. But on an off biopsies for 2 years
• High risk women (BMI>35 on oral progestogens) needs 6 monthly
assessment for 2 years and annual screening there after for follow up
• If bleeding needs further evaluation

16. Hysterectomy + BSO
• Indications
• Progression to atypical hyperplasia
• No regression following 12 months of treatment
• Recurrence
• Symptomatic
• If does not wish to have surveillance or treatment
• Premenopausal individualize oophorectomy, but B/L salpingectomy.
Oestrogen replacement therapy should be considered.
• Subtotal avoided

17. Endometrial ablation
• Not recommended
• Complete or persistent endometrial destruction cannot be ensured
and adhesion formation may preclude further histological surveillance

18. Atypical hyperplasia
• Total hysterectomy

19. Women who
have fertility
wishes
• MDT
• Counsel about the risk of underlying
malignancy
• Coexisting cancers
• Ovarian cancer – 4%
• Higher than stage1 ECa – 2%
• Metastatic disease – 0.5%
• Prior need
• Hysteroscopy
• MRI/CT
• Ca 125

20. LNG IUS or Oral progesterone
Follow up
• with 3 monthly EB
• Once 2 consecutive samples negative – Every
6monthly to 1year biopsies till hysterectomy
25% of live pregnancy rate
Results are better if
• Disease optimally suppressed
• Assisted reproduction techniques

21. Cervical
cancer
• Preventable
• Curable
• Long natural history
• Most common female malignancy in developing
countries
• 7th most common cancer in women worldwide
• Good screening had led to a dramatic reduction
in cervical cancer – 30% decrease from 1993-
2003 in UK

22. Cervical pre-invasive
disease

23. Natural history of HPV
• Genital infection of HPV acquire only
through sexual contact
• Both high and low risk forms occur
commonly in 16-25 yr group (10-30%)
• But most virus clears in 2-3 year by cell
mediated immunity and CIN regresses
(60-80%)
• Rest, infection persists and within 2-4
years causes CIN lesions
• Progression rate of CIN is 5% per year

25. Likelihood of
regression
Invasive cancer in 20
years
CIN1 60% 10% will become high
grade lesions
CIN2 45%
CIN3 30% 36%

26. • Virus enters the epithelium through a breach in skin integrity caused
by microtrauma
• It remain in the cytoplasm as episomes and can be cleared
• But sometimes enter the nucleus and this is called integration
• The cell no longer undergo apoptosis after 40-60 cell cycles and
instead become immortal. E6 and E7 oncoproteins which binds to p53
and RB respectively are responsible for this

27. • Prevalence of HPV in cervical cancers - 99.7%
• HPV infection is necessary
• But persistence is important
• 70% of cancers have High risk 16 and 18
• Above 30 yrs HPV incidence decline to about 5% but the regression
rate is much lower
• In a woman over 30 years with high risk HPV positivity the risk of
developing CIN 3 is 116 times compared to a control
• The whole process of early lesion to invasive cancer may take 15-20
years

28. Risk factors
• early onset of sexual activity
• multiple sexual partners (of self or of the partner)
• low socioeconomic status
• Tobacco smoking (2-fold)
• oral contraceptives (2.5-fold)
• other sexually transmitted infections like herpes simplex virus,
Chlamydia and bacterial vaginosis might play a role in the
progression of HPV infection to dyskaryosis
• immuno-compromise, including human immunodeficiency virus (HIV)
(5-fold)

29. Screening
• Cytology based
• HPV based
• Histology to confirm –
colposcopy based

30. Routine
screening
Negative
Routine
recall
Inadequate
Rpt in 3/12
Borderline/
low grade
HPV
Negative Intermediate
Initial
borderline
Rpt Cytology
in 6/12
Initial LSIL
Colposcopy
Positive
Colposcopy
High grade
Colposcopy

31. Colposcopy
< CIN 1
Routine recall
CIN 1
Untreated
12/12
cytology
follow up
CIN 1/2/3
Treatment
Test of cure in
6/12

33. cGIN
• Associated particularly with HPV 18
• Cytology is unsatisfactory and no colposcopic features
• Diagnosis is by chance during treatment of squamous pre-invasive disease
• 90% of the lesions occur 1cm from SCJ. But can occur anywhere in the
endocervical canal
• Can have skip lesions higher up in the endocervical canal. Therefore even
after treatment 15% have recurrence.
• This is associated with 50% of CIN and 40% of adenocarcinoma
• Therefore cone biopsy is needed to exclude occult invasive
adenocarcinoma. Endometrial biopsy to rule out abnormality higher up

34. Management
• Colposcopy and biopsy – Because higher percentage has concomitant CIN
• Punch biopsy is inadequate since disease often occurs at the crypts of the
glands
• Therefore for diagnosis and treatment conization is used
• Endometrial sampling
• Local excision – excision margins should be clear
• Fertility sparing surgery is a possibility provided that the margins are clear
• These people are at higher risk of recurrence
• 15% when margins free
• 50% when margins involved
• Hysterectomy

35. Vulval intraepithelial
neoplasia
• Premalignant condition of the vulva
• Cellular changes are limited to the epithelium. Does not
breech the basement memebrane

36. Unifocal
• Postmenopausal
• Non HPV
• Differentiated histology
Multifocal
• Premenopausal
• HPV related
• Interlabial grooves, posterior
forchette, perineum

37. Clinical features
Pruritus
Perineal pain
Dysuria
50% asymptomatic
Mass, ulcer
Altered appearance
Most multifocal, non hairy part
raised/verrucous white, red, brown,
pink, gray, macular lesion

38. Investigations
Multiple biopsies needed - histology shows
loss of organisation of squamous epithelium
with a variable degree of cytological atypia
which is graded as undifferentiated or
differentiated and by depth
Colposcopy to exclude CIN and VIN
If perianal lesions anoscopy

39. Treatment
Conservative
• Supervision
• Some may regress
spontaneously
Medical
• 5% Imiquimod
cream – Regression
shown in small
studies. But limited
follow up
Unlicensed use
• 5FU – not reliable
Unlicensed use
Local destruction
• laser
• cryotherapy
• photodynamic
therapy
• USS surgical
aspiration
• Recurrence higher
But good cosmesis
Surgery
• Can be mutilating
when multifocal
• Local excision –
Treatment of
choice for small
well circumscribed.
Recurrence is
lowest with
excision
• Vulvectomy –
Effective but
recurrence can
occur

40. If not treated
80% can have invasive cancer in 10 years
If treated
10%

41. • Extramammary paget’s is a rare form of VIN. It is associated with
cancer of the apocrine gland
• Follow up - Specially for VIN 3

42. Thank you