Gynecologic Cancers

Question 1

What percentage of women get cancer?

Answer 1

1/3 women at some point in their lives

Question 2

Relative incidence / mortality of gynecologic cancers

Answer 2

• Incidence: uterine > ovary > cervix

* Mortality: ovary > uterine > cervix

Question 3

Risk factors for endometrial cancer (7)

Answer 3

•Mainly related to estrogen exposure: obesity (estrogen is unregulated by adipocytes), nulliparous, late menopause, unopposed estrogen, atypical hyperplasia, diabetes, HTN

Question 4

Type I vs Type II endometrial cancer
Association to estrogen
Prevalence
Population
Aggression
Mutation
Histology

Answer 4

• Type I estrogen related. Type II not.
• 80% are type I, 15% are type II
• Pxs are younger / fatter in type I. Older / thinner in type II.
• Type I is less aggressive than type II
• Type I has mutation in PTEN and KRAS. Type II as mutation in p53.
• Type I has endometrioid histology (cells still columnar). Type II has serous histology (looks similar to ovarian cancer; cells not columnar, high N/C ratio, many mitoses)

Question 5

Most common presentation of endometrial cancer

Answer 5

Most common complaint is abnormal post / peri-menopausal bleeding.

Question 6

Indications for endometrial biopsy (5)

Answer 6

• Abnormal uterine bleeding – postmenopausal bleeding (always abnormal), perimenopausal intermenstrual bleeding, bleeding w/ hx of anovulation
• Postmenopausal women w/ endometrial cells on Pap test
• Thickened endometrial stripe via sonography

Question 7

Staging endometrial cancer

Answer 7

• Surgical staging includes cytology, TAH / BSO, and pelvic / aortic lymph node dissection.
• Stage 1a: less than 50% of myometrium involved
• Stage 1b: >50% of myometrium involved
• Stage 2: cervix involved
• Stage 3: Uterine serosa, adnexae, vagina, or pelvic / aortic node metastases
• Stage 4: bladder / bowel involvement, inguinal node, or distant metastases.

Stage 1 is most common (70%)

Question 8

Treating endometrial cancer (3)

Answer 8

• Surgery is primary treatment for endometrial cancer.
• Adjuvant postop therapy – used for stage II-IV
• Whole pelvic radiation + vaginal cuff boost: done for stage II / III
• Chemo

Question 9

Risk factors for recurrent endometrial cancer (5)

Answer 9

High grade (II / III), depth of myometrial invasion, tumor size (>2cm), invasion of lymph / vascular space, aggressive histologic cell type (serous)

Question 10

Treating recurrent endometrial cancer

Answer 10

Recurrent disease is considered incurable (except for isolated vaginal cuff recurrence in a woman who did not receive radiation). Recurrent disease is treated w/ platinum-based chemo

Question 11

Risk factors (4) and preventative factors (5) for ovarian cancer

Answer 11

• Increasing risk factors – age (post-menopausal; biggest risk), family hx, infertility / low parity / uninterrupted ovulation, hx of cancer (esp breast)
• Decreasing risk factors – OCPs, pregnancy, tubal ligation, trans-tubal factor, breast feeding

Question 12

Mutations in ovarian cancer
Low grade (4)
High grade
1 other

Answer 12

• Low grade tumors often have mutations in KRAS, BRAF, PTEN, and beta-catenin
• High grade tumors often have p53 mutation (most common mutation overall)
• BRCA 1 / 2 germline mutation associated w/ 35-65% lifetime risk

Question 13

From where do most ovarian cancers originate?

Answer 13

70% originate from surface epithelial cells (mesothelium). Many are now thought to arise from the fimbriated end of the fallopian tube.

Question 14

Ovarian cancer histology

Answer 14

Most are high grade, serous histology. High N/C ratio. Pyknotic. Stain for p53.

Question 15

Ovarian cancer presentation (5)

Answer 15

Most common complaint is bloating and early satiety. Others include ascites, weight gain (from ascites), and bowel obstruction may be present.

Question 16

Tumor marker for ovarian cancer

Efficacy

Answer 16

• CA 125 – elevated in 80% of advanced epithelial ovarian cancers.
• Poor sensitivity in stage I. Also poor specificity. NOT a screening test for general population.

Question 17

Diagnosing ovarian cancer (3)

Answer 17

Often suggested by CT or US, but surgical exploration / pathology is definitive.

Question 18

Staging ovarian cancer

Answer 18

• Staging is done surgically (like uterine cancer)
• I: confined to ovaries
• II: confined to pelvic organs
• III: spread to upper abdomen. Most common at presentation.
• IV: distant metastasis (lungs / liver).

Question 19

Treating ovarian cancer (4)

Answer 19

• Optimal therapy is TAH/BSO (total abdominal hysterectomy / bilateral salpingo-oophorectomy) + staging. May include infracolic omentectomy and lymph node examination.
• Reproductive conservation therapy may be better for younger women. Remove just 1 ovary and leave uterus.
• Debulking increases survival.
• Chemotherapy required in all pxs except stage Ia – All pxs should receive a taxane and a platinum.

Question 20

Prognosis of ovarian cancer after treatment

Answer 20

• 75% of women have a good response to chemo and are in remission after 6-8 cycles. Unfortunately, >50% of women in remission will recur w/in the first 3 years of completing treatment.
• Recurrent ovarian cancer is considered incurable.

Question 21

Follow-up for ovarian cancer

Answer 21

• Rectovaginal pelvic exam and CA125 every 3-4 months for first 2 years, then 6 months for 3 more years.
• CT scan only if sxs are present
• Discuss HRT (mainly for premenopausal women, which is rare), diet, exercise

Question 22

What is the most common cause of cancer death in women worldwide?

Answer 22

Cervical cancer

Question 23

Which strains of HPV are high risk for cervical cancer?

Answer 23

16 and 18

Question 24

Where does HPV virus most often infect?

Answer 24

Basal epithelium of mucosa. Transition b/w squamous and columnar epithelium is most susceptible.

Question 25

How does HPV DNA disrupt cell control?

Answer 25

HPV DNA may get incorporated into host DNA, which usually disrupts E2 protein → disrupts normal feedback, so E6 / 7 get overproduced. E6 / 7 normally blocks p53 and Rb, which cause apoptosis. Overall, not enough apoptosis → cancer.

Question 26

Signs / sxs of cervical cancer (6)

Answer 26

Abnormal / post-coital bleeding, foul vaginal discharge (tumor necrosis), pelvic pain, unilateral leg swelling / pain, pelvic mass, gross cervical lesion

Question 27

Cervical cancer histology

Answer 27

Koilocytes w/ perinuclear halo (filled w/ virus)

Question 28

Staging cervical cancer

Answer 28

• I: confined to cervix
• II: upper 2/3 of vagina / parametria involved
• III: lower 1/3 of vagina / parametria involved
• IV: distant disease, including bladder or rectal mucosa

Question 29

Who is recommended to get the HPV vaccine?

Answer 29

Males / females age 9-26

Question 30

Treating stage I a / b cervical cancer

Answer 30

• Stage Ia
• Conization – cut off abnormal part of cervix but leave normal cervix.
• Simple hysterectomy – used for micro invasive cancer
• Stage Ib
• Radical hysterectomy – removal of uterus, upper vagina, and pelvic lymph nodes. Preserve ovaries.
• Chemoradiation has equivalent survival to surgery. Used in pxs that can’t have surgery.

Question 31

Treating stage 2+ cervical cancer (3)

Answer 31

• Chemoradiation is mainstay of tx. NOT surgery due to poor margins.
• 4-5 weeks of external radiation to pelvis.
• 2+ implants (brachytherapy)
• Concurrent cisplatin chemo. Acts as radiation sensitizer and controls metastases.

Question 32

2 types of cervical cancer recurrence

Treatment

Answer 32

• Central pelvic recurrence – involves residual cervix, vagina, posterior bladder, or anterior rectum. Treat w/ radiation if this was not done before. If radiation was already done, may require en bloc removal of uterus, cervix, vagina, bladder, rectum, and sometimes vulva or peri-anal skin. Drastic, but has cure rates of 50%
• Others – chemotherapy is the only option. Very poor prognosis.