Prevention of Gynecologic Cancer

1. Prevention of
Gynecologic Cancer
Aboubakr Elnashar
Benha university Hospital,
Egypt
ABOUBAKR ELNASHAR

2. Prevention of Gynecologic Cancers: why?
TREATMENT
 Expensive
 Complicated
 Associated with loss of reproductive function
 Castration.
 Emotional and sexual
Mortality and Morbidity
 5 year survival rate for cancer ovary< 40%
ABOUBAKR ELNASHAR

3. Methods of Prevention
 Primary:
Avoidance of the precipitating & risk factors
 Secondary:
early detection
 Tertiary:
treatment or mitigation of damage
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4. I. Primary Prevention
 Fair evidence
 Statistically significant
 Practical
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5. 1. CERVICAL CANCER
Magnitude of the Problem: -
 500,000 new cases identified each year
 80% of the new cases occur in developing
countries
 At least 200,000 women die of cervical
cancer each year
 Cervical cancer is the third most common
cancer worldwide
ABOUBAKR ELNASHAR

6. Primary Prevention of Cancer Cervix
 Cervical cancer is a preventable disease
1-Avoidance of smoking
 2 fold excess risk
 dose response relationship
 current smokers > ex. smokers > non smokers
Mechanism:
 Nicotine, phenols, tars, are highly concentrated in
cervical mucous.
 Smoking act as a co carcinogen with HPV
 Low levels of plasma Beta carotene
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7. 2-Diet rich in vit C
30% lower risk
Mechanism:
 antioxidant
 enhancement of the immune
system
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8. 3.Barrier contraception (mechanical and chemical)
 Diaphragm. condoms
 Foam, spermicides
 contraceptive jelly
Mechanism:
 cervical carcinoma behaves as STD,HPV play a key
role.
 Use of barrier method decrease exposure to
infectious agents
 Spermicidal foam. jellies have demonstrated - anti
viral property
4.Alteration in sexual life and habits
ABOUBAKR ELNASHAR

9.  Cervical cancer is a preventable disease
 Primary prevention:
 Education to reduce high risk sexual
behaviour
 Measures to reduce/avoid exposure to HPV
and other STIs
 Secondary prevention:
 Treatment of precancerous lesions before they
progress to cervical cancer (implies practical
screening test)
 Now: HPV vaccines.
ABOUBAKR ELNASHAR

10. 2. PRIMARY PREVENTION OF
ENDOMETRIAL CARCINOMA
1. combined oral contraceptive pills
 Use for 2 years decrease incidence by 40%
 The longer the duration the greater the
protection
 Protection persists after discontinuation
ABOUBAKR ELNASHAR

11. Mechanism:
 Endometrial carcinoma is increased by
unopposed E stimulation
 The progestin in oral cc offsets the effect of
endogenous E production and causes
decidual changes in the endometrium
 Depot medroxy progesterone acetate
 Progesterone added to estrogen for HRT
ABOUBAKR ELNASHAR

12. 2.Normal weight females have
significant low risk
Mechanism
 Avoidance of Obesity minimizes the risk of
anovulation and unopposed E stimulation
 Adipose tissue converts androstendione to
esterone
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13. Uterine Cancer: Prevention
 Pregnancy
 Some hormonal contraceptives
 Combined Hormone Replacement
Therapy (HRT)
 Weight control
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14. 3. PRIMARY PREVENTION OF OVARIAN
CANCER
1.Combined oral contraceptive pills
 Use for as little as 6 months
 The longer the duration the greater the
protection
 A decade of oral cc reduces the risk by about
80%
 Protection persists after discontinuation
Mechanism
 Anovulation (Each ovulation expose the ovarian
epithelium to a definite risk of malignancy
transformation)
 Suppression of gonadotropines
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15. 2.Breast feeding
Mechanism
 anovulation
3.Tubal sterilization
Mechanism
 Isolation of the ovaries from carcinogens
imported from the external environment
4.Prophylactic oophrectomy during pelvic
surgery at 40- 50 years
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16. Ovarian Cancer: Prevention
 Pregnancy
 Oral contraceptives
 Breastfeeding
 Tubal sterilization
ABOUBAKR ELNASHAR

17. ABOUBAKR ELNASHAR

18. Molecular Targets for Cancer Prevention
Four Main Classes
a) genes in which altered expression or activation
drives induction of cancer and for which inhibitor
drugs are commercially available
(b) genes in which altered expression or activation is
shown to be causal in two or more models but for
which inhibitor/modulator drugs are not commercially
available
(c) molecular targets for which drugs are available
but of which the causal significance is unknown
(d) known and unknown molecular targets of
preventive dietary modifications
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19. II. Secondary Prevention
(Screening )
 Identifying pre clinical diseases
Asymptomatic people.
 Objective:
to reduce the incidence and the mortality from the
disease
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20. Epidemiology rankings
 Incidence
 Breast
 Cervix
 Ovary
 Corpus
 (vulva)
 Mortality
 (vulva)
 Ovary
 Cervix
 Breast
 Corpus
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21. Why?
 Ovarian (& cervical, vulval) cancer present as late-
stage disease – “silent killers”
 Endometrial cancer – abnormal bleeding
 Increased public awareness of breast cancer
ABOUBAKR ELNASHAR

22. WHO requirements for prospective
screening programs
 The condition should pose an important health
problem.
 The natural history of the disease should be well
understood
 There should be recognizable early stage
 Suitable acceptable test.
 Adequate facilities for the diagnosis and
treatment of the abnormalities detected.
 The cost of the screening program should be
balanced against the benefit it provides.
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23. Ovarian Cancer
Epidemiology
 Worldwide 165,000 cases (4.4% of cancers in
women)
 Highest incidence in N. America and N. Europe
 lifetime 1 in 70 women
 Less common in developing countries
 Worldwide 101,000 deaths annually (44,000 in
developing countries)
Sources: Parkin et al., 1999; Pisani et al., 1999.
ABOUBAKR ELNASHAR

24. Evolution of screening?
 Signs & symptoms
 Clinical examination
 Imaging (ultrasound + )
 Serology
ABOUBAKR ELNASHAR

25.  Signs & Symptoms
 (persistent) abdominal distension
 Unexplained upper GI symptoms
 Anorexia
 Unexplained weight gain or loss
 Excessive fatigue
 Progressive changes in bowel/bladder habit
 Unexplained back/abdominal pain
 Postmenopausal bleeding
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26.  “symptom survey” (pain+bloating+upper GI)
 57% sensitive for early disease
 80% sensitive for late disease
 90% specific for women > 50 yrs of age
 86.7% specific for women < 50 yrs of age
(Am Cancer Soc – Jan ’07)
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27.  Abdominal/pelvic examination
 Limited information
 Ovarian palpation difficult
 Adnexal mass not necessarily cancer or even
ovarian origin
 Poorly sensitive or specific
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28. Risk Factors
 White and North Europe.
 >40ys.
 Reproductive history: Nulliparous, Late age 1st
preg., Non users of OCP.
 +ve family history and past history of breast
endometrium and colonic cancer.
 Rubella and mumps.
 Talc, sanitary pads with talc.
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29.  Modalities:
1- Clinical (Annual bimanual gynecologic
examination).
2- Cul-de-sac aspiration.
3- Imaging techniques (TVS)
4- Tumour markers (CA 125 serum levels)
Screening of high risk group by CA125/TVS.
5- Immuno diagnosis.
6- Multimodels
 2/3 of cases are diagnosed in advanced stages.
 Non-specific presenting symptoms.
 No cost/effective screening program.
.
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30.  Imaging
 Ultrasound - adnexal mass
- prognostic features
- false +ve
- doppler studies
 Pelvic CT - retroperitoneal
 MRI - surface features
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31.  Serology - serum CA-125
 Elevated in 80% ovarian cancers (20% not)
 Elevated non-ovarian cancers
 Elevated in benign conditions
 Elevated during menstruation
 Should not be used alone for diagnosis
 Rising levels possible Ca, stable/decreasing
levels characteristic of benign cyst
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32. Ovarian cancer – risk assessment
 Demographics
 Women obese >50yrs of age
 ↑incidence in industrialised countries
 Ethnic – caucasian, Ashkenazi Jews
 Heredity – 5-10% cases (BRCA I/II)
 PMH other genital tract Ca esp breast
 hormonal – <menarche:>menopause
- nulliparity (?m/c)
- ovulation induction
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33. Ovarian cancer – early detection strategy
 Symptom survey >
50
 Risk assessment
+
 Nulliparous > 50 yrs
 PMH genital cancer
 FH cancer breast,
ovary, testes, colon
(BRAC I/II testing)
 Directed screening
 CA 125 assay(s)
 Pelvic ultrasound plus
doppler
ABOUBAKR ELNASHAR

34. Conclusion:
 no effective screening test for ovarian cancer in
the general population
 Benefit to screening is unproven
 Screening may result in more unnecessary
surgeries than new ovarian cancers
ABOUBAKR ELNASHAR

35. Cancer cervix
High risk groups
 Age of first sexual intercourse before 15 years.
 Prostitutes – multiple sexual partners
 Low socioeconomic
 Genital infection HPV.
 Smoking
 High parity
 Patient taking immunosuppressive drugs
 low beta-carotene intake
ABOUBAKR ELNASHAR

36. Modalities
• Pap Smear
• Visual inspection with acetic acid (VIA)
• Visual inspection with Lugols iodine (VIA)
• Visual inspection with acetic acid and magnification
(VIAM): Gynescope or Aviscope
• Colposcopy
• Cervicography
• Automated pap smears
• Molecular (HPV/DNA) tests
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37. BEFORE ACETIC ACID APPLICATION- Unaided
visual inspection of Cx – “Clinical Down staging”
NORMAL: -
•Smooth, pink
•Clear mucoid secretion
•Central hole-'external os'
Nulliparours-round
Multiparous-slit or cruciate
•Cervix in postmenopausal women is atrophic
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38. Screening in Low-resource Settings
Effective Safe Practical Affordable Available
Visual
Inspection:
AA
Yes Yes Yes Yes Yes
Visual
Screening:
Unaided
No Yes Yes Yes Yes
Automated
Pap Screening
Yes? Yes ? No No
HPV
Screening
Yes Yes ? ? Yes
Cervicography Yes? Yes ? ? Yes
HPV Vaccine ? ? Yes ? No
Source-Program for Appropriate Technology in Health [PATH] 1997.
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39. Uterine Cancer
Epidemiology
 142,000 cases worldwide
 42,000 deaths annually worldwide
 3.8% of all cancers in women
 Incidence is higher in developed countries
Sources: Parkin et al., 1999; Pisani et al., 1999.
ABOUBAKR ELNASHAR

40. Risk Factors
Old age
 Median age at diagnosis: 61 years
Lifelong estrogen exposure
 Early menarche
 Late menopause
 Anovulation
 Nulliparity
 Unopposed estrogen
replacement therapy
 Tamoxifen exposure
 Estrogen-secreting tumors
ABOUBAKR ELNASHAR

41. Other Risk Factors
 Obesity
 Diabetes
 Hypertension
 History of primary breast cancer
 Hereditary colon cancer
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42. PRE-INVASIVE LESIONS OF END.
Malig. PotentialPathology
Little or noneReplacement of usual
gland cell by cells
having cilia, sq. cells
Metaplasia
1-3% over 15yIrregular glands, minor
budding or out
pouching
Simle hyperplasia
3-4% over 13yBack to back glands,
budding, papillary
process, minor
stratification
Complex
hyperplasia
23% over 10yAtypisim + back to back
+ budding
Atypical hyperplasia
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43. Modalities:
1. Endometrial sampling
 Risks include discomfort, bleeding, infection, uterine
perforation (rare)
Aspiration curettage
Aspiration cannula
Brush cytology
2.Routine Pap smear:
inadequate and endometrial cytologic assessment is
too insensitive and non specific.
3.TVS color Doppler superior to other methods in
early detection of endometrial carcinoma.
Transvaginal ultrasound examinations
 Helpful in evaluating vaginal bleeding
4.Hysteroscopy: The lesion show frank dimply
appearance with irregular polylobed growing edge.
ABOUBAKR ELNASHAR

44.  Screening of unproven benefit
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45. Early vulvar cancer detection
High risk groups
 Post menopausal
 Dystrophy
 Chronic granulomatous lesion
 HPV virus
 DM- hypertension
 Smoking
ABOUBAKR ELNASHAR

46. PRE-INVASIVE LESIONS
 Vulva dystrophy:
Leukoplekia
Krauses vulva
Lichen simplex
 VIN: I, II & III
 Paget`s: may be associated with paget`s of breast.
ABOUBAKR ELNASHAR

47. Modalities:
 Colposcopy
 Acetic Acid test
 Toulidine blue test
 Biopsy
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48. Breast Cancer
Epidemiology
 Over 314,000 deaths
 17/100,000 incidence in N. Africa
 7.7/100,000 mortality in N. Africa
Sources: Parkin et al., 1999; Pisani et al., 1999.
ABOUBAKR ELNASHAR

49. Risk Factors
 Age
 Family history
 Nulliparity
 Younger age at menarche
 Older age at menopause
 Older age at first birth
 Fibrocystic disease with atypia
 Living in developed countries
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50. Clinical Features
 Palpable mass
 Mammographic abnormality
 Nipple discharge
 Mastalgia
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51.  Modalities:
1. Breast self-examination:
Monthly, starting at age 20
2. Clinical breast examination:
Every three years, age 20-39
3. Mammography
Annually, starting at age 40 *
Beginning at age 40, annual clinical breast
examination should be performed prior to
mammography. Most other affluent countries
recommend mammography every other year
between ages 50 and 70.
ABOUBAKR ELNASHAR

52. Chemoprevention
 Tamoxifen
 Raloxifene
 Letrozole
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53. Suggested Cancer Screening Guidelines
General health counseling and cancer evaluation
 All women should have a general health
evaluation annually or as appropriate, which
should include evaluation for cancer and
examination to detect signs of premalignant or
malignant conditions.
Breast cancer
 Mammography should be performed every 1- 2
years for women 40- 49 years of age and then
annually there after.
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54. Cervical cancer
 All women who are or who have been sexually
active or who have reached 18 years of age
should undergo an annual Pap test and pelvic
examination. After a woman had three or more
consecutive, satisfactory, annual cytological
examinations with normal findings, the Pap test
may be performed less frequently on a low risk
woman.
Endometrial cancer
 Screening all women for endometrial cancer
and its precursors is neither cost effective nor
wanted
ABOUBAKR ELNASHAR

55. Ovarian cancer
 No techniques that have proved to be effective in
reducing the disease specific mortality of ovarian
cancer are currently available.
Colorectal cancer
 After the age of 50 years, a digital rectal
examination should accompany the pelvic
examination and the annual fecal occult blood test
should be performed every 3-5 years.
Lung
 No available techniques are currently suitable for
routine screening.
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