World 10 most common cancer in
women (GLOBOCAN 2008)
Non – Hodgkin
Third most common cancer in women.
8.8 % of all female cancer.
Responsible for a total of 275,000 deaths; 58% were
reported from Asia.
6th most common women cancer.
More than 90 % of patients with uterine cancer are
more than 50 years old.
Cancer of the uterus has a much more favourable
prognosis than ovarian and cervical cancer with 5 –
year survival rates of around 80 – 90 % in developed
countries and 70 % in developing countries.
Cancer of the ovary is one of the most lethal
gynaecological malignancies due to late presentation,
poor respond to treatment and high recurrent rate.
3.7 % of all women cancer; with 4.2 % of all cancer
deaths in women.
Can be considered as sexually transmitted disease.
Early age of sexual activity predisposes to cervical
cancer. Relative risk is 2.5 if the age of the first sexual
exposure is < 18 years old.
Women with hx of HPV infection is also at a higher
risk. Women with multiple sexual partners have a
relative risk of 2.8 if the no. of partners > 4.
Multiparous women are at a higher risk. Women in
lower socio-economic class are at a higher risk.
Women who are married to a man with multiple
sexual partners are at a higher risk.
Cigarette smoking has been identified as a significant
risk factor by 2 – 5 folds.
Patients who are immunodeficient are at a higher
In-utero exposure to DES.
Women with uncircumcised sexual partner may be at
There are 3 modalities of cervical cancer prevention:
1. Primary prevention:
- prevention of HPV infection either through sexual
abstinence, healthy lifestyle and HPV vaccination.
2. Secondary prevention:
- detection and treatment of precancerous state
3. Tertiary prevention:
- detection and treatment of an early stage of cancer.
1. HPV vaccination
HPV is the primary aetiology of cervical cancer.
Following the limitations of secondary prevention:
- 2` prevention does not prevent HPV infection or
pre-invasive lesions of the cervix.
- lesion that has rapid progression rate may not be
detected in time.
- higher chances of missing the lesions in the cervical
- limited sensitivity and specificity.
- high cost and labour intensive.
Oncogenic types of HPV are estimated to cause
almost 100% of cervical cancer.
2 potential benefits of HPV vaccination:
- prevention of HPV-related precancerous and
- prevention of HPV-related benign lesions.
Currently 2 types of prophylactic HPV vaccines
available in the market:
- quadrivalent HPV vaccine against HPV 16,18,6,11
- bivalent HPV vaccine against HPV 16 and 18
2. Screening of cervical cancer
Screening of precancerous lesions and invasive
cervical cancer is secondary prevention.
It stops the progression of disease once it has already
Comprehensive analysis of data by International
Agency of Research on Cancer (IARC) showed:
- well organised screening programs were effective in
reducing cervical cancer incidence and mortality.
- the greatest reduction in the cervical cancer
incidence was in women aged between 30 and 49
years, for whom the focus of screening was the most
Target age range of a screening program was a more
important determinant of risk reduction than
frequency of screening, within the defined age range.
Screening interval every 2 – 3 years have been found
to be as effective as annual screening.
The protective effect of 5 years screening interval in
the organised screening program was still high
(> 80 %).
Screening every 2 years is approximately 50% more
expensive than screening every 3 years.
Risk of developing invasive cervical cancer is 3 – 10 x
greater in women who have not been screened. Risk
also increases with long duration following the last
normal screening test.
Type of screening tests
2. visual inspection
3. HPV testing
- Pap smear screening program significantly reduced
the incidence and mortality of cervical cancer.
- in UK, since the introduction of the organised pap
smear screening program in 1988, the incidence and
mortality rate of cervical cancer have fallen by more
- Pap smear is highly specific in detecting invasive
cervical cancer and HGSIL, but less specific in low
- pap smear is not very sensitive. Low sensitivity was
attributed to poor sample collection, incorrect slide
preparation and lab interpretation errors.
To reduce the false negative, sample from the
endocervix has to be taken. Cytobrush can obtain
more cell than Ayre’s spatula and cotton tip
Liquid – based cytology:
- introduced to increase the sensitivity and specificity
of cervical screening.
- more positive results with LBC.
- large reduction in unsatisfactory smear in LBC
- per test cost of LBC is higher.
2. Visual inspection
Direct visualisation of the cervix after application of
either acetic acid 3-5% or Lugol’s iodine.
A result is obtained immediately and treatment can
be performed at the same time.
3. HPV testing
HPV DNA is identified in almost all 99.7% verified
cases of cervical cancer worldwide.
4 potential roles of HPV testing:
1. triage of women with equivocal cytology
2. following up of patient after treatment of CIN
3. HPV testing in “see and treat” approach
4. HPV testing as primary screening test
Optoelectronic device - for optical and electrical
assessment of the cervix to detect any abnormal
- HPV genotyping
- HPV mRNA
- HPV viral load
- HPV integration
Asymptomatic at an early stage.
Abnormal vaginal bleeding = speculum exam.
Most common - post coital bleeding.
Passing out blood stained mucus.
Copious foul smelling PV d/c.
Pelvic pain, urinary problems and constitutional
symptoms – strong indication of advance stage
Pyometra – if the d/s has obstructed the uterine
outflow tract. Presents with pelvic pain, purulent
vaginal d/c and fever.
Invasion posteriorly may cause tenesmus and PR
late stage – SOB, bone pain, severe headache,
neurological problems, LOA and LOW.
Lymphatic obstruction may result in lower limb
Venous outflow obstruction can lead to DVT.
Type of endometrial cancer
Broadly classified into 2 main categories:
Type I endometrial cancer:
- is related to exposure to unopposed endogenous or
- frequently arise on a background of atypical
- have an association with obesity, nulliparity, insulin
resistance and hyperoestrogenism.
- usually well differentiated and have a better
- has no association with predisposing factors.
- example – uterine papillary serous, clear cell
- patients tend to be elderly and thin.
- have a poorer prognosis.
80% of endometrial cancer are type I.
Prolonged exposure to oestrogen.
High level of endogenous oestrogen is often seen in
obese women, patients with PCOS and oestrogen
50% of patients has BMI > 25 kg/m2.
In premenopausal women, obesity causes insulin
resistance, ovarian androgen excess, anovulation and
chronic unopposed oestrogen.
DM and HPT – risk factors independent of their
association with obesity.
The use of COCP for 1 year decreased the risk of
endometrial cancers by more than 40%.
Women on combined HRT have also been found to
have lower risk.
About 5% of endometrial cancer is hereditary, a/w a
hereditary non-polyposis colon cancer syndrome
Smoking is said to reduce the risk.
Pregnancy has a natural protective effect because of
high production of progesterone by placenta.
Risk factors for Type I
- >30 lb ideal BW 3x
- >50 lb ideal BW
Late menopause 2.5x
Heavy PMB 4x
Unopposed exog. E
untx complex atypical
hyperplasia – 29% will
Endometrial hyperplasia: progressing to
- simple hyperplasia (no atypia) 1%
- complex (adenomatous, no atypia) 3%
- atypical simple (cystic w atypia)
- atypical complex (adenomatous w atypia)
Can be prevented by treating the precursor lesions
either by hormonal or surgical treatment.
Adding a progestogen for at least 10 - 12 days per cycle
Women with amenorrhoea or oligomenorrhoea
(including women with PCOS) should be treated with
cyclical progestogen, to avoid prolonged exposure of
the endometrium to a high level of oestrogen.
Withdrawal bleeding of 3 monthly is sufficient to
prevent endometrial pathology.
Suggestions of a protective effect of high phyto-oestrogen
consumption among post menopausal
The use of IUCD and tubal ligation have also been
associated with a lower risk.
Weight reduction and physical activities to achieve
ideal body weight, can reverse the effect of prolonged
exposure to a high level of oestrogen.
Pregnancy is a physiological protection, due to a high
level of of progesterone produced b the placenta.
The use of COCP for 1 year decreased the risk by >
40%. Also known to reduce the incidence of ovarian
There is no effective screening method for
For available methods - accuracy in asymtomatic
population is limited.
In women presenting with PMB, TVS showing ET of
5mm or less and negative endometrial sampling, have
nearly 100% negative predictive value.
Majority of patients with endometrial cancer are
Most common presenting Sx is PMB.
Abnormal PV d/c.
abnormal PV bleeding in 80% (including PMB and
irregular menses in premenopausal women).
Pressure Sx due to uterine enlargement.
Sx indicating extrauterine spread.
Epithelial cancer is infrequent below 40 years old.
Peak rate is at 70 - 74 years age group with the
incidence of 57/100,000 population.
Ovarian cancer at the older age group carries a poorer
1. Reproductive factors:
Parous women have 30 - 60% less risk compared to
The birth of the first child reduces the risk by 45%.
Every further pregnancy reduces the risk by 15%.
Breast feeding reduces the risk.
Tubal ligation is also associated with lower risk.
Ovulation induction agent increases the risk by 2-3 x,
if taken for > 12 ovulatory cycles.
OCP reduces the risk by 30 - 60 %.
History of breast cancer increases the risk.
Early menache and late menopause are risk factors.
Slightly increased risk with HRT.
2. Genetic factors:
Lifetime risk in general population is 1.6%.
Increased to 4% in women with a first degree relative
Increased to 7% when 2 first degree relatives are
5-10% of all epithelial ovarian ca results from
The frequency of BRCA 1 mutation is about 1 in 800.
62% of patients with epithelial ovarian cancer have a
mutation of p53.
3. Environmental factors:
Incidence highest in industrialised countries except
Incidence lowest in under developed and developing
High intake of meat and animal fat diet increases the
Low fat diet may reduce the risk in postmenopausal
Obesity has been attributed to risk of ovarian cancer.
OCP (chemoprevention) has the highest protective
effect against ovarian cancer.
Taking OCP for at least 5 years reduces the relative
risk of by 50%.
Tubal ligation and hysterectomy reduces the risk.
Prophylactic oopherectomy is often performed
together with hysterectomy for benign conditions.
Prophylactic oopherectomy to women with BRCA1
and BRCA2 mutations after the age of 30 - 35 years,
reduces the risk by 80%.
For women with BRCA1 and BRCA2, recommended to
do TVS and CA125 levels every 6 - 12 months, in
women age 25 - 35 years old.
Genetic testing for BRCA1 and BRCA2.
There is no effective screening method.
75 - 85% of patients already has peritoneal spread at
the time of the diagnosis.
Most common presentation:
- abdominal discomfort
- abdominal pain and distension
- GIT symptoms e.g. nausea, dyspepsia, constipation.
Diagnosis of early stage cancer is usually made by
abdominal and pelvic examination.
In premenopausal women, functional cyst is rarely >
8cm, and will resolve after 2-3 months without
Adnexal mass in pre-menarchal and post menopausal
women has a higher likely hood of being malignant.