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 21Under 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 high-risk 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 mid-endocervical canal

– Original squamous epithelial layer- covering 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 lymph-adenectomy)

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 TxSurgical Consult gynecological oncologist, who

can address both medical and surgical needs

Questions?