GYNECOLOGIC CANCER

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GYNECOLOGIC CANCER

• Edward L. Cohen, MD
• Chief Section of Gynecology
• Department of Surgery
• VA Palo Alto Healthcare System
• And
• Associate Clinical Professor OB/Gyn
• Stanford University
• School of Medicine

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GYNECOLOGIC CANCER

• Annual Meeting
• NOVA
• Milpitas California
• 26 January 2008

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GYNECOLOGIC CANCER

• Endometrium
• Most common gyn cancer in the US
• 6 of all cancer in women
• 2-3 lifetime risk

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GYNECOLOGIC CANCER

• Endometrium
• Age Mean is 61 yrs.
• Menopausal 75-80
• Pre-menopausal 20-25
• 5

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GYNECOLOGIC CANCER

• Endometrium
• Types
• Endometrioid 89
• Adeno-squamous 4
• Papillary Serous 3
• Clear cell

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GYNECOLOGIC CANCER

• Endometrium
• Prognosis depends on cell type, grade, and stage.
• Overall, endometrioid has a better prognosis than
  adeno-squamous, papillary serous, or clear cell.

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GYNECOLOGIC CANCER

• Endometrium
• Increased risk factors
• Age
• Estrogen
• Obesity
• Diabetes (Type II)
• PCOS
• Late menopause (55yr) (Define
  menopause)
• Nulliparity
• Tamoxifen
• Hereditary nonpolyposis colorectal
  cancer
• (HNPCC)

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GYNECOLOGIC CANCER

• Endometrium Risk factors and RR
• Estrogen 10 (3-15)
• Obesity 3-4
• Diabetes 2.8
• PCOS 3
• Late menopause 2
• Nulliparity 2
• Tamoxifen Increase of 6/1000
• (Decrease
  breast 121/1000)
• HNPCC 40-60 lifetime risk

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GYNECOLOGIC CANCER

• Endometrium
• Decreased risk factors
• --Add progestin to ERT (RR1)
• --Use of OCPs for at least 12 mos
• (RR0.5). Effect lasts at least
• 15 years.
• --Exercisedecreases obesity and
• favorable changes in immune function
• and sexual and metabolic hormone
  levels and
• growth factors
• --Diet of fresh fruit, vegetables, whole
  grain foods

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GYNECOLOGIC CANCER

• EndometriumRisk Factors
• Estrogen (unopposed)
• Exogenous
• ERT
• Tamoxifen
• Endogenous
• Chronic anovulation
• PCOS and obesity

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GYNECOLOGIC CANCER

• Endometrium
• Exogenous estrogen
• ERT effects can be reversed by
• addition of a progestin.
• Tamoxifen and SERMs
• Receptors differ in breast and
• endometrium. Stimulates endom.

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GYNECOLOGIC CANCER

• Endometrium
• Endogenous
• Chronic anovulation (PCOS and
• obesity) means no progesterone
• in premenopausal women.
• Obesity--Adrenal precursors to E1
• and E2
• --Decreased SHBG
• --Increased insulin-like GF

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GYNECOLOGIC CANCER

• EndometriumRisk Factors
• HNPCC (Lynch Syndrome II) is a
• mutation of DNA mismatch repair genes
• MLH1, MSH2 6, and PMS2 most often.
• High risk for tumors of endometrium,
• ovary, stomach, small bowel, hepato-
• biliary system, urologic system.
• In half of the women, endometrial and
• ovarian cancer PRECEDE colon cancer.

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GYNECOLOGIC CANCER

• Endometrium
• HNPCC should be considered if hx
• of three relatives with colorectal,
• endometrial, small bowel, urologic
• system
• One first degree relative
• Two successive generations
• At least one under age 50.

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GYNECOLOGIC CANCER

• Endometrium
• PresentationAbnormal Bleeding
• EVEN ONE DROP OF BLOOD IN A MENOPAUSAL WOMAN NOT
  ON HORMONES DEMANDS WORKUP
• 10-20 will have endometrial cancer, and
  probability increases with age.

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GYNECOLOGIC CANCER

• Endometrium
• Screening should be sensitive early in the
• disease so clinical course can be altered.
• It should be specific to reduce women
• needing diagnostic tests.
• Decreased sensitivity means higher false negative
• Decreased specificity means higher false positive

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GYNECOLOGIC CANCER

• Endometrium
• Screening Methods As no reliable,
  inexpensive, non invasive method exists,
  screening in asymptomatic women is not warranted.
  
• 90 have abnormal bleeding, and about
• 70-75 of women are stage I if we test only
  after symptoms arise. 5 year survival is 90-95.

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GYNECOLOGIC CANCER

• Endometrium
• Screening Methods
• Pap is very insensitive
• Ultrasound is insensitive in
• asymptomatic women.
• Endometrial biopsy is sensitive, but
• invasive, painful, and often QNS
• for diagnosis. (Recommended by ACS
• after age 35 for HNPCC, but no data)

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GYNECOLOGIC CANCER

• Endometrium
• Variation of screening considerations
• Of women with endometrial cancer
• under age 50, and one first degree
• relative with HNPCC related cancer,
• 23 will have a gene mutation and
• should be screened for that. (Beware other
  cancers)

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GYNECOLOGIC CANCER

• EndometriumPrevention
• Progestin with estrogen
• Diet, Exercise and Weight control
• If genetic mutation, AND done with
  reproduction, offer hysterectomy and BSO

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GYNECOLOGIC CANCER

• Ovary
• 5 of all cancers in women.
• 23 of all gynecologic cancer
• 1.7-2 lifetime risk

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GYNECOLOGIC CANCER

• Ovary
• Ovarian cancer affects females of
• ALL AGES
• Prognosis depends on cell type, grade and
  stage.

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GYNECOLOGIC CANCER

• Ovary
• Tissue types
• EpithelialAbout 85-90 (50 yrs)
• Germ cell10-15 (
• Gonadal stroma5-10
• Mesenchymal

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GYNECOLOGIC CANCER

• Ovary
• Epithelial
• Serous
• Mucinous
• Endometrioid
• Clear cell
• Undifferentiated

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GYNECOLOGIC CANCER

• Ovary
• Germ Cell
• Dysgerminoma
• Endodermal Sinus
• Embryonal
• Choriocarcinoma
• Polyembryoma
• Immature Teratoma
• Gonadoblastoma

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GYNECOLOGIC CANCER

• Ovary
• Gonadal Stroma
• Granulosa cell
• Theca cell
• Sertoli-Leydig

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GYNECOLOGIC CANCER

• Ovary
• Mesenchymal
• Lymphoma
• Sarcoma

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GYNECOLOGIC CANCER

• Ovary
• Symptoms are all non specific
• Abdominal swelling/bloating
• Abdominal/Pelvic pressure or pain
• GI upset/dyspepsia
• Urinary frequency
• EXAMINE THE PATIENT. Routine CAT
• scan may take weeks to perform.

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GYNECOLOGIC CANCER

• Ovary
• Cancer should be suspected in any woman
  between 40 and 80 with persistent gi symptoms
  cannot be diagnosed.
• Diagnosis is difficult. 70 of diagnoses
• are stage III or IV.

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GYNECOLOGIC CANCER

• Ovary
• Decreased Risk Factors (Prevention)
• Parity
• OCPs
• ??Low fat diet
• Increased Risk Factors
• Age
• Genetic Mutation-- Only 10 of cancers.
• (BRCA1 and 2, and HNPCC)

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GYNECOLOGIC CANCER

• Ovary Decreasing RiskPrevention
• Effect of Parity
• Term Pregnancies RR
• 0 1
• 1 0.6
• 2 or 3 0.5
  
• 4 or more 0.33

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GYNECOLOGIC CANCER

• Ovary Decreasing RiskPrevention
• Effect of OCPs
• Duration of use RR
• Never 1
• 3mos-4yrs 0.65
• 5-9 yrs 0.4
• 10 yrs or more 0.2

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GYNECOLOGIC CANCER

• Ovary
• Increase Risk Factor
• BRCA1 35-45
• BRCA2 15-25
• If reproduction is not an issue, offer BSO.

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GYNECOLOGIC CANCER

• Ovary Screening
• There are no reliable data that ANY mode of
  screening is effective in improving the length
  and quality of life in women with ovarian cancer.

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GYNECOLOGIC CANCER

• Ovary
• Screening
• -Asymptomatic
• -Find at early stage
• -Reasonable return for effort
• -Reliable testssensitivity and
• specificity

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GYNECOLOGIC CANCER

• Ovary
• Higher SENSITIVITY, lower false neg
• Higher SPECIFICITY, lower false pos

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GYNECOLOGIC CANCER

• Ovary
• Screening methods
• Pelvic examination
• CA-125
• Ultrasound
• Future use of tumor markers

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GYNECOLOGIC CANCER

• Ovary
• Screening
• Pelvic examNeither sensitive or
• specific. Estimated 10,000 to find 1
• early stage ovarian cancer.

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GYNECOLOGIC CANCER

• Ovary Screening CA-125
• Less than 50 of stage I will have
• elevated levels and OTHER
• conditions raise the CA-125

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GYNECOLOGIC CANCER

• Ovary Screening
• CA-125 is elevated
• GynEndometriosis, adenomyosis, fibroids,
  functional ovarian cysts, menstruation, benign
  neoplasms, PID
• Non-GynLiver disease (acute and chronic
  infectious and alcoholic), pancreatitis, CHF,
  colitis, diverticulitis, pneumonia, pericarditis,
  renal disease, SLE and PAN.

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GYNECOLOGIC CANCER

• Ovary Screening
• CA-125 with other tumor markers, particularly
  HE4, look promising.
• As cancers are abnormal cells, they make
  abnormal proteins. If patterns can be found that
  are both sensitive and specific we might have
  good screening tests. (Proteomics)

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GYNECOLOGIC CANCER

• Ovary Screening CA-125
• Marker Sensitivity Specificity
• CA-125 69.5 62
• With HE4 73 95

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GYNECOLOGIC CANCER

• Ovary Screening Ultrasound
• University of Kentucky
• 14,500 asymptomatic women
• 10 yrs
• 57,200 scans
• 180 surgical explorations
• 11 invasive epithelial cancers found.
• 8 were stage I or II
• FOR EACH CANCER FOUND there were
• 16 surgeries and 5,200 ultrasounds.

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GYNECOLOGIC CANCER

• Ovary Screening Ultrasound
• Largest study to date using COMBINATION. If
  CA-125 high, had ultrasound.
• 41 surgeries
• 11 ovarian cancer (4 early stage)
• 8 women with negative screens
• developed cancer.

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GYNECOLOGIC CANCER

• Cervix
• 12 of gynecologic cancers
• Mean age is 47.
• 20 of cases in women 65yrs
• 10 of cases in women 75yrs

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GYNECOLOGIC CANCER

• Cervix
• Prior to Pap smears, this was the most common
  gynecologic cancer worldwide.
• In developed nations, there has been a 75
  DECREASE in the past 50 yrs, mainly due to
  detection and treatment of pre-invasive disease.

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GYNECOLOGIC CANCER

• Cervix
• Types
• Squamous Cell 85-90
• Adenocarcinoma 10-15
• Numerous others

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GYNECOLOGIC CANCER

• Cervix
• Etiology is oncogenic HPV
• Risk Factors
• Early onset coitus
• Multiple partners,
• or high risk partner
• Smoking is co-carcinogen
• Immunosuppression

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GYNECOLOGIC CANCER

• Cervix Smoking Effect
• Group RR
• HPV negnon smoker 1
• Smoker 2
• HPV pos 15
• HPV pos smoker 66

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GYNECOLOGIC CANCER

• Cervix ScreeningMajor methods
• PapEither traditional or liquid based
• About equal in early stage disease.
• (60-75 senstivity 86-100 specific for
• HSIL)
• HPV testing
• Primary screenbeing studied.
• Some studies100 sens, but LOW
• specificity.
• Supplemental to ASCUS Pap, currently

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GYNECOLOGIC CANCER

• Cervix Screening
• Frequency of screening is undergoing continual
  re-evaluation. There are guidelines, but these
  must be modified for the individual patient.

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GYNECOLOGIC CANCER

• Cervix HPV
• 80 of sexually active women will
• acquire HPV.
• Most will be cleared in 12-18mos
• 80-90 will resolve in 2-5yrs.
• Persistence and subtypecancer.

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GYNECOLOGIC CANCER

• Cervix HPV
• Over 120 types
• Oncogenic types 16, 18, 45, et.al.
• Non oncogenic 6, 11, et.al.

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GYNECOLOGIC CANCER

• Cervix HPV
• Oncogenic incorporate into host
• genome.
• Association with SCCaCx
• 16 60
• 18 20
• 45 7

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GYNECOLOGIC CANCER

• Cervix HPV
• Non-oncogenic types are associated with
  formation of condylomata, an emotional and
  quality of life issue.
• Oncogenic virus doesnt cause condylomata, and
  non-oncogenic types dont lead to cancer

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GYNECOLOGIC CANCER

• Cervix PreventionImmunization
• HPV quadrivalent vaccine contains virons,
  virus-like particles (NOT live virus) of 6 11
  (warts), and 16 18 (cervical, vaginal and
  vulvar cancer).
• An ounce of prevention is worth a pound of
  cure.

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GYNECOLOGIC CANCER

• Cervix PreventionImmunization
• In non-exposed individuals, it is 95-100
  effective.
• If exposed, 80-90 effective, like other
  vaccines.

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GYNECOLOGIC CANCER

• Cervix PreventionImmunization
• Cross protection
• A strong immune response will cross
• protect to related types.
• Antibodies to cross protect
• 16 31, 33, 52, 58
• 18 39, 45, 59

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GYNECOLOGIC CANCER

• Cervix PreventionImmunization
• Additional benefits
  Cancer HPV related
• Anal 70
• Vulvar, vag, penile 50
• Oropharyngeal 20-40

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GYNECOLOGIC CANCER

• Cervix PreventionImmunization
• Schedule Initial, 2mos, 6mos.
• Population Females 9-26 yrs.
• Ongoing studies show effective to give to age
  45.
• Effective in males also, but not yet approved.
• Pregnancy Category B