Gyn Oncology
Tory Davis, PA-C
Introduction

Facts:
– Mortality from cervical cancer has been reduced
by 70% since the advent 50 years ago of the pap
smear.
– Between 1980-1990, Maine’s cervical cancer
mortality rate was ranked third in the nation.
Now we’re fourteenth in the US among
Caucasians.
– Risk of developing cervical cancer over a lifetime
is 3.7% among never screened vs 0.3% of those
screened regularly
Frequency of Pap test
screening:

ACS and ACOG’s recommendation:
– Annual pap and pelvic exam
 Start at age 21
 Under the age of 30
– Pap smears q 2 years
– Follow up ASC-US with reflex HPV test
 Age
30-64 and over
– Pap smears plus HPV DNA test every
three years if results are negative. If
results are discordant, additional testing
will be done
Stop at age 65-70 if 3 nl paps in a row
and no cancer in >10 years
 No more pap after hysterectomy for
benign indication, unless hx of cervical
cancer

Risk factors for cervical
malignancies
– Women whose male sexual partners have had
other sexual partners with cervical cancer
– Women with current or prior HPV infection
– Women with current or prior HSV infection
– Women who are infected with HIV or other STIs
– Women who were DES-exposed in utero
– Women with immunosuppression
– Smokers and abusers of other substances,
including alcohol
– Women who have a history of gyn cancer
– Women of lower socioeconomic status
Human Papilloma Virus





Most common STI world-wide
Estimated that 6.2M people in the US
become infected with the virus annually
Lifetime chance of HPV infection is proposed
to be 80%-85% in sexually active individuals.
> 100 types of HPV, most are harmless.
Some (HPV 6 and HPV 11) cause genital
warts, but not cancer.
High risk HPV for cancer include: 16 &18,
which cause >70% of all cervical cancers
– Also 31,33,35,39,45,51,52,56,58,59,68,and 69
Human Papilloma Virus

New(ish) vaccine (Gardasil) for HPV 6,
11, 16, 18

NB- Even people who contract a highrisk HPV will not necessarily develop
cancer.
Normal Cervix



Clear comprehension of the normal cervix
aids understanding abnormal alterations of
the cervix.
Each cervix demonstrates a unique stage
of dynamic epithelial transformation that
occurs throughout a women’s life.
The physiologic landscape of the normal
cervix enables malignant transformation to
occur when the conditions are appropriate.
Anatomy of the Cervix

Cervix:
– distal portion of the uterus
– length - 3.5 cm; diameter 2.5 cm
– endocervical canal - extends from the
internal to external os
– ectocervix - outside of the cervix, seen
during speculum exam
Normal Cervix

Epithelial cells:
– Columnar - mucous secreting epithelium
covering the proximal and midendocervical canal
– Original squamous epithelial layercovering the vagina and distal ectocervix
– Squamocolumnar Junction - boundary
between the squamous and columnar
epithelium
Normal Cervix
(continued)

Squamocolumnar Junction – may occur anywhere on the ectocervix or
endocervix
– Starts in endocervix and “rolls out” to
ectocervix around puberty
– may change at various times as a result
of hormonal variations
 sexual
activity
 pregnancy
Normal Cervix
(continued)


Eversion - seen as a red area on the outside of the
cervix as a result of the columnar epithelium. As the
uterus and cervix grow during puberty and
adolescence, the original SCJ “rolls out”, or everts
from inside to outside the cervix. Also seen during
pregnancy and with oral contraceptives.
Transformation Zone - area between the original
and new SCJ.
– In the menopausal years, the uterus and cervix decrease
in size, and the new SCJ comes to lie upward into the
endocervical canal, often out of direct visual contact.
Obtaining the Optimal
Pap

Obtain a pap smear:
– Mid cycle
– No intercourse or douching x 48-72 hours
– No intravaginal medications within the
past 72 hours
Technique of
Cytological Screening

Important steps in obtaining an adequate
sample:
– Collect cells prior to bimanual exam
– Avoid contaminating the sample with lubricant (controversial)
– Pap first, STD testing after
– View entire cervix before sampling
– Carefully remove large amounts of discharge
before sampling, so you can see the cervix
Technique of
Cytological Screening

Important steps in obtaining an adequate
sample:
– Do not sample if heavy menses
– Treat vaginitis first (if pt likely to come back for
the pap) to avoid inflammation-related ASCUS
– Obtain the ectocx first and then the endocx to
avoid bleeding from the brush
– Develop system to minimize fixation time or use
liquid-based (ie: Thin Prep)
– Gently rotate brush for endocervical sample
False Positives

False Positive
– Vigorous use of the endocervical
brush
– Airdrying artifact if not using liquid
medium
– Severe atrophy
– Previous irradiation or chemotherapy
– Infection/inflammation/repair
False Negatives
Smears lacking diagnostic cells
 Sampling errors
– inadequate technique
– failure to obtain an adequate number of
cells
– failure to sample TZ component (no endocx
cells)
 Inappropriate technique in spreading cells on
slide or incomplete mixing
 Non-shedding lesion
 Screening or interpretive error
Pap Test Screening
Techniques
Glass slide, traditional
 Liquid - based system

– Thin prep  Advantages:
less mucous, fewer thick cell
clumps higher rate of dx abnormalities and
lower rate of unsatisfactory
 Disadvantages: laboratory processing is
more labor intensive with increase of $15-$20
more than conventional methods
Pap results
Reported by The Bethesda System
 But first, some history…

– Dysplasia
– CIN categories
CIN







Previously called “dysplasia”
Cervical Intraepithelial Neoplasia
Infection with HPV
Disordered growth of epithelial lining of
cervix
Mild= CIN I
Moderate= CIN II
Severe= CIN III
Dysplasia



“Disordered growth”
Disruption of the ordered growth of cervical
cells
Normal distribution:
– bottom layer is made of round young cells.
– as cells mature they rise to the surface and
flatten out, so that on the surface the cells are
flat.
Normal
Moderate dysplasia

In dysplasia and carcinoma-in-situ
all of the abnormalities are confined
to the surface lining (or "skin") of
the cervix
– In invasive cancer, cells invade tissue
under the surface. NB the difference.
Bethesda

ASCUS
– ASC-H
LSIL
 HSIL
 AGUS
 Why doesn’t the Bethesda system
include an “invasive cancer” option?

ASCUS




Atypical cells of unknown significance (abnl
cells not quite dysplastic, CIN I)
Usually caused by mild infection or
inflammation
1 in 20 paps
80% are of ASCUS paps are normal
– 13% will be low grade, 7% high grade lesions

Next step: test for oncogenic HPV strains
LSIL or LGSIL
Low grade intraepithelial lesion
 Encompasses HPV/mild dysplasia/CIN
1
 1/600 may become cancer
 50% resolve spontaneously
 Management age-dependant

– Under age 20, repeat cytology 12 months
– Otherwise, colposcopy
HSIL/ HGSIL
High-grade intraepithelial lesion
 Encompasses moderate and severe
dysplasia, CIN 2 and CIN 3, CIS
 1% risk of cancer
 Colposcopy with biopsy

– Followed by destruction of abnormal
tissue (if confirmed and not resolved by
biopsy)
AGCUS

Atypical glandular cells of undetermined
significance
– “glandular cells that show nuclear atypia
appearing to exceed reactive or reparative
changes but lacking unequivocal features of
adenocarcinoma.” (Bethesda System)
– May include endocervical cells, endometrial cells



0.2-0.8% of all paps
20-50% have more serious lesion
Must have colposcopy, possibly cervical
cone biopsy
Cervical Changes

Carcinogen Exposure - cause an
abnormal maturation process at the
transformation zone and begins the
process of intrepithelial neoplasia.
– Approximately 95% of squamous
intrepithelial neoplasia occurs within the
transformation zone.
 Cigarette
smoking
 Intercourse at a young age
 HPV (16,18,31,33,35,39,45,51,52,56,and 58)
Management of Abnl
Pap

See algorithm pdf
Invasive Cervical
Cancer
US: 10k cases/year with <4k
deaths/year
 Worldwide: 370,000 cases/year with
50% mortality rate
 Prognosis dependent on stage at
diagnosis

Cervical Cancer and
CIN Treatments






Local Excision- ie: biopsy, usually done
during colposcopy
Cryocautery- destroy abnl tissue by freezing
Laser Therapy
LEEP- Loop Electrosurgical Excision
Procedure
Cone biopsy
Hysterectomy
VIN
Vulvar Intraepithelial Neoplasia
 80% positive for HPV (usually HPV-16)
 Assoc with smoking
 MC CC: pruritis
 Multicentric origin (as opposed to
single point origin of cervical cancer)

VIN




Lesions vary in appearance- single,
multiple, flat, raised, papules, white, red….
1-2% of women with cervical dysplasia have
multifocal ds involving vagina, vulva,
perineum, perianal
Range- mild dysplasia to carcinoma in situ
Dx with colposcope and bx
Vulvar Cancer
5% of gynecological cancers
 Postmenopausal women
 Long hx vulvar irritation, pruritis,
bloody discharge
 Lesions: early look like dermatitis, late
can be indurated, cauliflower-like or
ulcerated
 Dx with bx

Vaginal Cancer
3% of gyn cancers
 Early- asymptomatic
 Then painless bleeding from ulcerated
tumor
 Late vaginal bleeding, pain, wt loss
 85% squamous cell cancers

Endometrial cancer
US lifetime risk 1.3% (Black women)
2.4% (Caucasian)
 Usually diagnosed age 60s, but can
occur in 20-30 year olds
 25% pre-menopausal
 Abnormal endometrial bleeding

Estrogens and
Endometrial Ca

Hyperestrogenism is a causative factor
– Estrogen unopposed by progesterone, ie:
PCOS, chronic anovulation, delayed menopause
– Exogenous estrogens
– Nulliparity


Estrogens stimulate endometrium,
progesterones are anti-proliferative
Endometrial cancer not related to sexual
activity
Presentation
Abnl vaginal (endometrial) bleeding,
usu post-menopausal
 No screening program
 Physical exam unremarkable
 Endocervical cytology MAY reveal
carcinoma
 Better results with aspiration cytology
or endometrial bx

Testing
Pap- Presence of endometrial cells on
cervical smear of post-menopausal
women assoc with endometrial cancer
in 2-6 % asx women and up to 25% of
women with post-menopausal bleeding
 Hysteroscopy- can increase dx
accuracy. Also can promote transtubal
spread to peritoneal cavity
 CT- pelvic anatomy
 MRI- identifying myometrial invasion

CA-125
Well-established tumor marker for
ovarian cancer
 May be elevated in endometrial cancer
as well
 NOT for screening
 Limited use for management

Endometrial ca tx
Surgical- hysterectomy, bilateral
salpingo-oophorectomy, staging
(pelvic and peri-aortic lymphadenectomy)
 Radiation can be curative, but 20%
lower cure rate than surgical, (so if it
were MY mom, I’d go with surgery)

Ovarian Cancer
3-4% of cancer in women
 4th most-frequent cause of cancer
deaths in women

 Why?
Lifetime risk of developing ovarian
cancer 1.4%
 Lifetime risk of death from ovarian
cancer 1%

Etiology



90% sporadic, 10% genetic predisposition
Incessant ovulation  lots of opportunity for
gene mutations
Protective:
OCPs, pregnancy, hx breastfeeding…Why?
Also bilateral tubal ligation…why?

Risks: diets high in fats, increased BMI
Presentation
Insidious
 Non-specific GI complaints

– Nausea, dyspepsia, altered bowel habits,
early satiety, sensation of pelvic weight

Menstrual abnormalities- in 15% of
reproductive-aged patients
Dx

Suspicion, good history, good exam
– 10% of masses <10 cm missed on physical
exam
– Attention to nodes: supraclavicular, inguinal and
umbilical- Sister Mary Joseph node


Pelvic US: good sensitivity, poor specificity
CA 125- not as screening for low-risk
women, but good for dx
– Especially coupled with ultrasound
– Low CA-125 does NOT exclude the dx


CT can delineate retroperitoneal structures
MRI best for info about the nature of the
neoplasm
Ovarian Cancer Tx
 Surgical

Consult gynecological oncologist, who
can address both medical and surgical
needs
Questions?