Gynecologic Cancer Screening

CANCER SCREENING
OG Quest 2022

Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H, Sion Hospital
Joint Treasurer, FOGSI (2021-2024)
Vice President, MOGS (2021-2022)
Member Oncology Committee, SAFOG (2020-2021) (2021-2023)
Dean AGOG & Chief Content Director, HIGHGRAD & FEMAS Courses
Editor-in-Chief, FEMAS & JGOG Journal
54 publications in International and National Journals with 81citations
National Coordinator, FOGSI Medical Disorders in Pregnancy Committee (2019-2021)
Chair & Convener, FOGSI Cell Violence Against Doctors (2015-16)
Member, Oncology Committee AOFOG (2013-2015)
Coordinator of 11 batches of MUHS recognized Certificate Course of B.I.M.I.E at
L.T.M.G.H (2010-16)
Member, Managing Committee IAGE (2013-17), (2018-20)
Editorial Board, European Journal of Gynaec. Oncology (Italy)
Course Coordinator of 3 batches of Advanced Minimal Access Gynaec
Surgery
(AMAS) at LTMGH (2018-19)
MOGS Special Award for Outstanding Contribution to Women’s Health 2021
Pride of FOGSI award 2020-2021
Doctors Excellence Award in OBGY category at ADMH Maharashtra Excellence Award
DR. NIRANJAN CHAVAN
MD, FCPS, DGO, MICOG, DICOG, FICOG, DFP
,
DIPLOMA IN ENDOSCOPY (USA)

SUCCESS STORY – THE PAP
SMEAR
• Developed by Dr George Papanicolaou in 1928 and
implemented since the 1940s.
• The Pap smear has been the most successful test that
brought down cervical cancer incidence and mortality by
70%.
• In developed countries, cervical cytology programs
involved screening of sexually active women annually, or
once every 3-5 years.

NEED FOR SCREENING
• Do we need to screen for Preinvasive Lesions of the
Cervix and why?
- YES
1. Sufficient burden of disease to pose a serious public
health problem.
2. Identifiable and treatable long precancerous phase.
3. Simple, non-invasive tests.
4. Effective treatments are available.

• Use of Pap smear has resulted in the
decline in cervical cancer over the last
50 years.
• Thus, screening for preinvasive lesions
of the Cervix is a must to reduce the
disease burden especially in developing
countries like India.

SCREENING MODALITIES
1. HPV testing
2. Cytology
3. VIA
4. Newer advances

PRIMARY HPV VS CO-TEST
• As per FOGSI GCPR guidelines – Co-testing i.e. combined
Cytology and HPV testing is the preferred screening
method in good resource settings for 30-65 years.
• Although primary HPV testing is the preferred screening
modality in 30-65 years age group, there is need for more
Indian data on the validity of primary HPV testing

CO-TESTING ALSO HAS THE FOLLOWING
BENEFITS
• Negative predictive value is
higher.
• Earlier diagnosis.
• A negative co-test helps us have
better spacing for screening.

WHEN TO START AND STOP?
• Screening very young women is associated with
relatively higher rates of unnecessary evaluation
and treatment of lesions that would otherwise
regress.
• Therefore, with Cytology the screening should
start at 21 years and with Co-test or Primary
HPV or VIA it should start at 30 years.
• Frequency - Annual screening has NO
advantage, rather leads to an increased number
of unnecessary colposcopies and is not
recommended for any category.

• Thus, women aged 30-65 years should preferably be screened with primary HPV
testing or combined cytology and HPV testing (co-testing) every five years.
• In Low resource situations, Ministry of Health and Family Welfare recommends five-
yearly screening with VIA till the age of 65 years.
• It is expected that this group of women will receive screening at least one to three
times in their lives.

• Women over 65 years with previous adequate
negative screening and no history of CIN 2+ within
the last 20 years need not be screened.
• Adequate negative prior screening means three
consecutive negative cytology results or 2
consecutive negative co-tests within the 10 years prior
to ceasing of screening, with the last test having taken
place within the last five years.
• In women who have undergone hysterectomy with a
report of CIN 2+ lesions, screening should be
continued for 20 years from the age of surgery.

HPV TESTING
1. Negative HPV test
provides greater
reassurance against
CIN 3+ in the
subsequent five to
seven years than
cytology alone.
2. HPV testing can not
differentiate between
persistent and
transient infection,
therefore it has 3%–
4% lower specificity
than cytology.

CO-TESTING
1. Co-testing leads to earlier
diagnosis of CIN 3+ and
Cancer.
2. Incorporating HPV with
cytology helps in finding
more AIS than cytology
alone
3. Negative co-test allows
spacing of screening in
every five years.
4. Co-testing in women
younger than 30 years
would lead to an increase
in unnecessary work-up
procedures without a
corresponding decrease in
cervical carcinoma
incidence because of
increased probability of
clearance of infection by
the immune system.

VIA TESTING
1. VIA screening was
associated with 31%
reduction in cervical cancer
mortality and a better
compliance in screened
population than controls
(86.3% versus 72.3%).
2. In a WHO Modelling study
- once in lifetime VIA -
@35years reduces lifetime
relative risk by 25-36% and
if done twice @35 and 40
years — reduces lifetime
RR by an extra 40%.
3. VIA is a feasible method to
initiate mass screening in
resource-poor settings
which lack an organized
screening program.

INTRODUCTION
• Ovarian cancer is one of the most common gynecologic cancers that rank third after
cervical and uterine cancer.
• It also has the worst prognosis and the highest mortality rate.
• Although ovarian cancer has a lower prevalence in comparison with breast cancer, it
is three times more lethal.
Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019;11:287-299.
Published 2019 Apr 30. doi:10.2147/IJWH.S197604

• The high mortality rate of ovarian cancer
is caused by asymptomatic and secret
growth of the tumor, delayed onset of
symptoms, and lack of proper screening
that result in its diagnosis in the advanced
stages.
• Thus, silent killer is a name that has been
given to this cancer.
Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world:
epidemiology and risk factors. Int J Womens Health. 2019;11:287-299.
Published 2019 Apr 30. doi:10.2147/IJWH.S197604

BGCS GUIDELINES(2019) RECOMMENDATION
• CA125 and pelvic ultrasound scan (+/- TVS as
indicated) should be considered the initial
investigations for post-menopausal women presenting
with signs or symptoms of ovarian cancer.
• Women with an RMI of ≥250 should have further
investigations and be referred to the specialist
gynaecological centre MDT.

• There is currently no role for organized screening programmes in women considered
at low risk of development of ovarian cancer .
• The role of ovarian cancer screening in women at high risk of ovarian cancer has yet
to be established.
• Risk-reducing salpingo-oophorectomy (RRSO) prevents development of epithelial
ovarian cancer and reduces mortality in women at high risk for epithelial ovarian
cancer.

SCREENING METHODS
Screening for Ovarian Cancer are:
• Transvaginal ultrasound (TVU),
• Measurement of serum CA-125,
• A tumor-associated antigen also known as MUC 16,
(or the combination of both)
• Liquid Biopsy using patient’s Blood/Plasma

EVIDENCE FAVORING SCREENING
• Patients with BRCA 1 or BRCA 2 mutations.
• Those with strong family history of ovarian
cancers.
• Ovarian cancer screening is not recommended
for women without risk factors.

CONCLUSION OF THE STUDY
• For women with increase risk, after evaluating risks and
benefits, ovarian cancer screening with CA-125 and/or
transvaginal ultrasonography can be done.
• In women at inherited risk, usually with mutations in
ovarian cancer susceptibility genes, should receive
screening by a combination of transvaginal
ultrasonography and CA-125.
• For patients with mutations in BRCA1 or the mismatch
repair genes, MLH1, MSH2, and MSH6, screening should
begin around 30-35 years of age.

RECENT ADVANCES IN OVARIAN
CANCER SCREENING
• Liquid Biopsy:
Liquid biopsies are derived from serum, plasma, or other body fluids and may provide
noninvasive biomarkers.
• MUC 16 Gene:
MUC16 is the gene that encodes the peptide moiety of the CA125 molecule.

LIQUID BIOPSY
• Currently, ‘liquid biopsies’ are a hot
topic in cancer research.
• Circulating tumor cells, cell-free (cf )
desoxyribonucleic acid (DNA), cf
micro ribonucleic acid (microRNAs),
Exosomes shed into the blood stream,
can be seen as surrogate for the tumor
itself.
• Their potential to improve early
diagnosis is theoretically present but
transition to the clinic is still far

MUC 16 GENE
• MUC16 is the gene that encodes the
peptide moiety of the CA125 molecule.
• MUC16 domains provide novel
opportunities to develop new assays and
refine current tools to improve the
sensitivity and specificity of CA125 for
population-based screening guidelines.

MUC 16 GENE
• CA125 is a multivalent molecule
and various proteolytic fragments of
CA125 are detected in the
commercially available assays.
• More so, its levels might be
increased in other non-malignant
conditions.
• We might be able to increase the
sensitivity and specificity of the
CA125 assay by grouping and
categorizing patients based on
which copy of MUC16 they carry to
adjust the quantitative measurement.

• Currently, no evidence supports benefits of screening for ovarian cancer in the
general population.
• Multimodal methods with serial measurements of CA-125 seem to outperform single
threshold measurements of CA-125 or transvaginal ultrasound alone.
• There are several limitations that still need to be overcome before implementing
liquid biopsies into clinical decision making.
• We need a screening strategy that can detect ovarian and tubal cancer in
asymptomatic women even earlier in its course and in a larger proportion of women.

RISK FACTORS
• Nulliparity
• Late menopause (>52yrs)
• Obesity
• Diabetes Mellitus
• Unopposed estrogen therapy
• Tamoxifen
• Atypical Endometrial Hyperplasia

• Non-invasive test for endometrial cancer is sufficiently
sensitive and specific for screening.
• The thickness of the endometrium on transvaginal
sonography is a sensitive test for detecting endometrial
cancer in postmenopausal patients.
• However, sensitivity is estimated to be 20 percent
lower in asymptomatic compared with symptomatic
patients, and specificity is low.
• Thus, many patients would end up needing an
endometrial biopsy.

TRANSVAGINAL SONOGRAPHY
It is done to assess
• Endometrial thickness
• Other endometrial pathologies like Polyp,
endometrial collection, cervical extension.
Cut off for ET in Postmenopausal for endometrial
hyperplasia is >4mm

The interpretation of characteristic findings on TVS:
A. Cystic endometrial changes: s/o Polyps
B. Homogenous thickened endometrium: s/o Hyperplasia
C. Heterogenous thickened endometrium: s/o Malignancy

ENDOMETRIAL SAMPLING
• Office endometrial biopsy is an effective diagnostic technique that is
simple to perform, does not require anesthesia, and is generally well
tolerated by the patient.
• There are now many devices for performing endometrial biopsies in the
outpatient setting.

Pipelle’s biopsy
Advantages:
• Inexpensive, OPD procedure, no need of dilatation or
anesthesia.
• Can be used without tenaculum.
• Causes less uterine scraping.
• Increased patient acceptance.
• Successful in obtaining adequate tissue sample in >95%
cases.

Explora
The disposable Explora Model by Cooper
Surgicals incorporates a long nylon curette
with Randall-type cutting edge, stylet and
Vacu-Lok syringe that adjusts suction from
approximately 15- to 20-inch Hg negative
pressure (6 cc to 12 cc).

Tao brush
It is a small flexible brush used
for endometrial biopsy. Tissue
upto 1.5-2 mm depth can be
obtained. It gently brushes the
entire endometrium so as to
gather complete sampling. It is
less painful and covers wider
surface area.

Vabra Aspirator
Disposable set for endometrial biopsy
VABRA® is a suction curette for
endometrial biopsy. Set includes
flexible straight catheter, with blunt
point and side-ports to allow suction
and collection of the endometrial
tissue, test-tube with cap and spoon,
universal pipe-fitting for aspirators.

Hysteroscopy
• Enables to visualize the entire endometrium and to take
biopsy from the selected area and reduce the chance of
missing early lesion.
• Reserved for situations with:
cervical stenosis/patient tolerance doesn’t permit
adequate evaluation by aspiration.
Bleeding recurs after a negative EB.
Specimen obtained is inadequate to explain AUB.

WORLD HEALTH ORGANIZATION (WHO)
OLD CLASSIFICATION OF ENDOMETRIAL
HYPERPLASIA (1994)
Type of Hyperplasia Percentage
Typical
Simple 1
complex 3
Atypical
Simple 8
complex 29

WORLD HEALTH ORGANIZATION (WHO)
NEW CLASSIFICATION OF ENDOMETRIAL
HYPERPLASIA (2014)
• Non-atypical endometrial hyperplasia (benign hyperplasia)
• Atypical endometrial hyperplasia
According to ACOG Committee 2018, endometrial thickness of <4mm or less
on transvaginal USG has a greater than 99% negative value for endometrial
cancer.

LYNCH SYNDROME
• The American College of Obstetricians and
Gynaecologists suggests endometrial biopsy every
one to two years beginning at age 30 to 35 years
• Surveillance is continued until risk-reducing
hysterectomy is performed.

INCIDENCE
Rare
Elderly women 70 – 80yrs
2/3 of cases are diagnosed in late stages
90% have visible lesion
90% Squamous Ca
Paget's disease of the labium majus. A bright scarlet, slightly raised,
velvety plaque with clearly defined serpiginous edges.

SCREENING MODALITIES
Colposcopy
Acetic Acid test
Toluidine blue test
Biopsy
Vaginoscopy showing multifocal acetowhite HPV lesions after
application of 5-percent acetic acid

STRATEGY
Assessment if
• Symptomatic, postmenopausal
• Other evidence HPV genital disease
• Symptomatic Lichen Sclerosus
Refer to gynae oncologist
• Pagets Disease
• Melanoma-in-situ
• VIN III
VIN 3 with extensive perineal and perianal involvement

RECOMMENDATIONS
Follow up of vulval dermatoses (LS).
Chronic pruritis vulvae should be investigated.
Look at the vulva whenever doing colposcopy
Follow up cases of CIN, more liable to develop VIN
Follow up HPV related changes, warts.
Biopsy any:
suspicious lesion
pigmented/hyperkeratotic area.
Early stage squamous cell cancer of the vulva.

High-grade vulvar lesions
Low-grade vulvar lesions
• Referred to as vulvar low-grade squamous
intraepithelial lesions (vL-SIL).
• These are benign lesions (flat condyloma
or HPV effect) associated with low-risk
HPV infection.
• VIN usual type (uVIN), are associated with
high-risk HPV infection, and can progress
to invasive vulvar cancer.
• Differentiated VIN lesions (dVIN), develop
in chronic skin lesions (like lichen
sclerosus), and have a potential for
malignant transformation
VIN CLASSIFICATION (2015)

MANAGEMENT OF VULVAR
INTRAEPITHELIAL NEOPLASIA (VIN)
• Excisional:
– Wide Local Excision
– Simple vulvectomy
– Skinning vulvectomy
– Laser excision
Ablative:
– CO2 laser ablation
– Cavitational ultrasonic surgical ablation
• Topical application:
– 5-Flurouracil cream
– Imiquimod cream

SCREENING FOR FALLOPIAN
TUBE CANCER
• CA-125 blood test
• Ultrasound exam
• Abdominal/Pelvic CT (computed tomography) scans
• MRI (magnetic resonance imaging)
• PET (positron emission tomography)
• Chest X-ray

SYNOPSIS
CERVICAL CANCER
HPV testing
Cytology
VIA
Newer advances
FALLOPIAN TUBE
CANCER
CA-125 blood test
Ultrasound exam
Abdominal/Pelvic CT
MRI Chest X-ray
VULVAR CANCER
Colposcopy
Acetic Acid test
Toluidine blue test
Biopsy
ENDOMETRIAL
CANCER
TVS
Endometrial sampling
OVARIAN CANCER
TVS
CA-125
MUC 16
Liquid Biopsy

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