Brachytherapy is also used for adjuvant or primary treatment - External beam radiotherapy (EBRT) to whole pelvis +/- vagina - Brachytherapy (low dose rate or high dose rate) to vaginal cuff or entire vagina - Adjuvant chemotherapy with radiotherapy improves survival in high-risk disease 14-Dec-19 Saeed Salman MD 38

1. CERVICAL CANCER
Saeed Salman, MD
Radiotherapy Unit
Oncology Institute
Rambam Health Care Campus

2. ANATOMY
14-Dec-19 Saeed Salman MD 2
The uterus:
A hollow, thick-walled, pear-shaped, muscular organ, 7 to 8 cm long, 5 to 7
cm wide, and 2 to 3 cm thick, usually bent anteriorly (anteflexed).
The uterus may be posteriorly retroverted, especially in older women who
have a small uterus.
The most superior part is called the fundus, superior to the line joining
the entrance of the fallopian tubes.
The middle portion is the body, enclosed between layers of the broad
ligament and is freely mobile.
The inferior portion is called the isthmus or lower uterine segment
(LUS). The wall of the uterus has three layers:
the outer serosal layer; the middle myometrium, which is approximately
12 to 15 mm of muscle through which the main blood vessels and
nerves flow; and the inner coat called the endometrium.

3. ANATOMY
• The cervix rests inferior to the LUS.
• The entire uterine cervix structure is
normally bent anteriorly (anteverted).
• approximately 3 by 3 cm .
• predominantly a fibrous organ.
• External os is central in the rounded vaginal
region, bounded by the anterior and
posterior lips of the cervix, extending
inward to the internal os, the endocervical
canal, and endometrial canal.
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4. ANATOMY
• The uterus is partially covered by peritoneum in its fundal
and posterior portions
• Anteriorly : bladder
• Lateral : broad ligaments
• attached to the surroundings by :
• broad and the round ligaments
• The main artery supplying the uterus is the
uterine artery, which originates from the anterior division of
the hypogastric artery.
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5. ANATOMY
• The uterus including the uterine cervix
has a rich lymphatic network
• Paracervical  External iliac (obturator
nodes are the innermost component)
 hypogastric lymph nodes.
• No lymphatic vessels run in the
vesicouterine space
• Pelvic lymphatics drain into the
common iliac and the para-aortic
lymph nodes (PALNs).
14-Dec-19 Saeed Salman MD 5
(Anatomical Chart Company, Lexington, SC.)

6. EPIDEMIOLOGY
• Over the last 80 years, the relative morbidity and mortality of locally
advanced invasive cervical cancer has declined in the United States
and Europe because of effective screening and treatment of
preinvasive lesions.
• 50% of women who develop cervical cancer have never been
screened, and another 10% have not been screened within the
previous 5 years.
• However, in the last decade, incidence rates of invasive carcinoma
have remained relatively constant due to population growth and
aging.
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7. New cases and death
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>60,000 cases of carcinoma in situ
CA CANCER J CLIN 2019;69:7–34

8. EPIDEMIOLOGY
• Worldwide, cervical cancer remains
the most common gynecologic cancer
and the fourth most common
malignancy in women.
• majority of cases are in Africa:
• Paucity of screening measures
• immunodeficiency because of HIV
• More common in areas where
women have less access to screening,
including:
• parts of Asia, Africa, and Central and
South America
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CA CANCER J CLIN 2019;69:7–34

9. Survival
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CA CANCER J CLIN 2019;69:7–34

10. Human Papillomavirus
• >90% of cervical cancers are related to the presence of human
papillomavirus (HPV) and are contracted via sexual intercourse
• HPV is:
• A small, double-stranded deoxyribonucleic acid (DNA) virus
• HPV-16 and HPV-18 in majority of cases
• Less frequent subtypes 31, 33, 35, 39, 45, 51, 52, 56, and 58
• HPV genome integrates into the host cell chromosomes
• six early and two viral proteins
• E5, E6, and E7 alter cellular proliferation
14-Dec-19 Saeed Salman MD 10

11. Human Papillomavirus
• E6 and E7, are typically expressed in HPV-positive
cervical cancer cells
• The E6 protein inactivates the major tumor
suppressor p53; this causes chromosomal
instability, inhibits apoptosis, and activates
telomerase.
• The E7 protein affects the retinoblastoma protein
(Rb), resulting in a loss of regulation of the cell’s
proliferation and immortalization
• Endometrial-like cervical cancer was HPV-negative,
occurred in 5% of cases
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12. Human Papillomavirus
Prevalence :
• Peaking at ages 25 to35 years
• <15% of exposed women develop persistent infection that results in
dysplasia
• Majority of women clear the infection within 2 years
• Cervical cancer may develop 10 to 20 years after initial exposure to
HPV
14-Dec-19 Saeed Salman MD 12

13. Human Papillomavirus
Risk Factors:
• Social factors:
• Early age of first intercourse
• A history of multiple sexual partners
• A male partner with a history of multiple sexual partners
• A large number of pregnancies
• A history of sexually transmitted disease, including gonorrhea, chlamydia, herpes simplex
virus II, and/or HIV
• Partners with a history of penile carcinoma
• Circumcision is controversial as a protective factor
• Prenatal exposure to diethylstilbestrol (DES)  clear cell adenocarcinoma
• Cigarette smoking
• Intrauterine device use may decrease cervical cancer risk, potentially through an
increase in cellular immunity triggered by the device
14-Dec-19 Saeed Salman MD 13

14. HPV Vaccination
• First approved in the United States in 2006 for girls and women ages 9
to 26 years
• Now available for boys ages 9 to 26 years, with the goal of eradicating
HPV-related gynecologic, penile, anal, and oropharyngeal cancers
• In 2015, results of a 9-valent HPV vaccine were reported, showing
significant activity against HPV types 31, 33, 45, 52, and 58 in addition
to 6, 11, 16, and 18.33
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15. 9-valent HPV Indication
• Indication for GARDASIL 9
• GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention
of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types
16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6,
11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.
• GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal
cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic
lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts
caused by HPV Types 6 and 11.
• GARDASIL ® 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate
the necessity for girls to continue to undergo recommended cervical cancer screening
later in life. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it
has been recommended by a health care professional.
14-Dec-19 Saeed Salman MD 15

16. 9-valent HPV Dosage and Administration
• GARDASIL 9 should be administered intramuscularly in the deltoid region of
the upper arm or in the higher anterolateral area of the thigh.
• For individuals 9 through 14 years of age, GARDASIL 9 can be administered
using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second
dose should be administered 6–12 months after the first dose. If the
second dose is administered less than 5 months after the first dose, a third
dose should be given at least 4 months after the second dose. For the 3-
dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6
months.
• For individuals 15 through 45 years of age, GARDASIL 9 is administered
using a 3-dose schedule at 0, 2 months, and 6 months.
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17. Routes of Spread:
Cervical cancer can spread by:
• Direct extension: may involve uterine corpus, vagina, parametria,
peritoneal cavity, bladder, or rectum.
• Ovarian involvement by direct extension of cervical cancer is rare; (0.5% in
SCC and 1.7% ofadenocarcinomas)
• Lymphatic spread
• Hematogenous dissemination: the most common sites are the lungs, liver,
and bone
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18. PAP SMEAR SCREENING
• The American College of Obstetrics and Gynecology guidelines
published in 2012 state that :
• Pap smear screening should begin at age 21 years
• Regardless of sexual activity status
• Continue every 3 years until age 30 years
• After age 30, women have the option of having Pap smears every 3 years, of
having Pap with HPV testing every 5 years
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19. When to Stop Screening
• Stop at age 65 for women with adequate negative prior screening, no
CIN2+ within the last 20y.
• Definition of adequate negative screening:
- 3 consecutive negative Paps
or
- 2 consecutive negative HPV tests
(Tests within 10 years of stopping; most recent within 5 years.)
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20. CLINICAL PRESENTATION
• Asymptomatic – abnormal cervical smear
• Vaginal bleeding
• Postcoital bleeding
• Abnormal vaginal discharge
• In advanced disease
• Pelvic or lower back pain, which may radiate along the posterior side of the
lower extremities
• Bowel or urinary symptoms, such as pressure-related complaints, hematuria,
hematochezia, or vaginal passage of urine or stool
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21. STAGING
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Int J Gynecol Obstet 2019; 145: 129–135

22. DIAGNOSTIC WORKUP
Examination
• Pelvic examination – speculum, bimanual, and rectovaginal examination
for palpation and inspection of the primary tumor, uterus, vagina, and
parametria
• Examination for distant metastases – palpation of groin and supraclavicular
lymph nodes
• Cervical biopsy: the diagnosis of cervical cancer is made based upon
histologic evaluation of a cervical biopsy
• Colposcopy with directed cervical biopsy
• Endocervical curettage
• Conization
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23. • PET has a higher
sensitivity than CT and
higher specificity than
MR in detecting bone
metastases
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24. TREATMENT – early stage
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25. TREATMENT – locally advanced stage
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26. TREATMENT – metastatic disease
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27. Endometrial Cancer

28. ANATOMY
• The average adult uterus is about 8 cm long, 5 cm wide, and 2.5 cm
thick
• divided into the fundus, body (corpus), and cervix
• The uterine cavity is lined by endometrium, made up of columnar
cells forming many tubular glands
• The lymphatic drainage for the body of the uterus is mainly to the
obturator and internal and external iliac lymph nodes
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29. EPIDEMIOLOGY
• The most common gynecologic cancer
• The fourth most frequently diagnosed cancer in women in the United
States
• The estimated number of newly diagnosed cases is 61,880, with a
probability of 1 in every 35 women (2.8%)
• The expected number of deaths from endometrial cancer in 2018 is
12,160
• The sixth leading cause of death from cancer in women
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30. 14-Dec-19 Saeed Salman MD 30
CA CANCER J CLIN 2019;69:7–34

31. RISK FACTORS
• Etiology remains unknown
• Unopposed estrogen is the main risk factor
• early age at menarche
• late age at menopause
• Nulliparity
• Obesity : 38.4% of endometrial cancer worldwide could be attributed
to high body mass index (BMI)
• After menopause, the major source of estrogen is via peripheral conversion
• Non–insulin-dependent diabetes mellitus and hypertension (secondary to
obesity?)
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32. RISK FACTORS
• Estrogen-only hormone replacement therapy and sequential oral
contraceptives
• Tamoxifen
• Hereditary nonpolyposis colorectal cancer (HNPCC)(Lynch syndrome),
probably accounts for <5% of all endometrial cancer cases
• lifetime cumulative risk of endometrial cancer for women with HNPCC
is 40% to 60%
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33. CLINICAL PRESENTATION
• Postmenopausal vaginal bleeding, which is reported by 80% to 90%
• Vaginal discharge
• Abnormal Papanicolaou smear
• Thickened endometrium on routine transvaginal ultrasound
• Advanced disease:
• urinary or rectal bleeding, constipation, pain, lower extremity lymphedema,
abdominal distension due to ascites, and cough and/or hemoptysis
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34. NATURAL HISTORY
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5-year survival rate by extension:
limited to the endometrium or with <50% myometrial invasion 91%
extended to adnexa/serosa/positive peritoneal cytology 66%
regional lymph node involvement 57%
bladder or rectal involvement 25.5%
with distant spread 20%

35. DIAGNOSTIC WORKUP
• H&P:
• Careful inspection of external genitalia, vagina, and cervix, rectal exam, and bimanual pelvic
exam. Attention for enlargement of uterus, or tumor extension to cervix, vagina, or
parametrium.
• Labs:
• CBC; optional: LFTs and CA-125 for high-risk subtypes.
• Imaging:
• TVUS
• CXR
• MRI is preferred imaging modality for preoperative local staging
• PET/CT remains best imaging modality for detecting LN metastases
• Biopsy:
• Gold standard is biopsy under hysteroscopy
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36. 14-Dec-19 Saeed Salman MD 36

37. TREATMENT PARADIGM
• Surgery:
• TAH/BSO (simple or type I hysterectomy) is standard of care for early disease
• Radical hysterectomy is done for cases of gross cervical invasion
• Omental and peritoneal biopsies are performed for high-risk disease
• Sentinel lymph node mapping to complete pelvic and PA lymphadenectomy
• Complications:
• Lymphedema (8%–50% risk depending on number of LNs removed, adjuvant
CHT/RT, preoperative NSAID use).
• Others surgical complications
14-Dec-19 Saeed Salman MD 37

38. TREATMENT PARADIGM
• Chemotherapy:
• Adjuvant for high risk tumors (carboplatin/paclitaxel)
• Concurrently with radiotherapy (weekly cisplatin) in selected cases
• Radiation
• Adjuvant therapy after TAH/BSO
• Primary therapy for pts who are not candidates for surgery
• vaginal cuff brachytherapy
• Toxicity:
• Acute: Fatigue, diarrhea, nausea, myelosuppression, dysuria, urinary frequency.
• Late: Vaginal stenosis, vaginal dryness, rarely RT cystitis, proctitis, sacral insufficiency
fractures, bowel obstruction, fistula.
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39. Ovarian Cancer
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40. INCIDENCE
• Estimated 22,530 new cases in 2019
• 1 in every 72 women
• higher among women with familial and known genetic predisposition to this disease
• 13,980 deaths in 2019
• Ovarian cancers are composed of:
• Epithelial tumors
• Sex cord–stromal tumors
• Malignant germ cell tumors of the ovary
• and metastatic cancers to the ovary - stomach or gastrointestinal tract known as Krukenberg tumors
• approximately 90% Epithelial ovarian cancers (EOCs)
• The most common subtype of EOC, the high-grade serous lesion, most commonly arises from the fimbriated
end of the fallopian tube
• Associated with mutation in breast cancer susceptibility gene 1 or gene 2 (BRCA1 or BRCA2) in approximately
10% to 15%of cases.
• Chemosensitive at diagnosis.
14-Dec-19 Saeed Salman MD 40

41. ETIOLOGY
• Risk factors:
• Age
• Family history (firsk degree 3-7X increased risk)
• Infertility – nulliparity
• Environmental:
• Highly industrial countries
• Protective factors:
• Increasing parity
• Oral contraceptive pill (OCP) use
• Salpingo-oophorectomy
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42. Epidemiology
• Highest age-adjusted incident in the industrialized nations
• >8/100,000 in north America and Europe
• <3/100,000 in Asia and Africa
• Median age at diagnosis 60 - 64 years
• Older than 65  worse prognosis
• Lifetime risk of EOC associated with
• Germline BRCA1 mutation > 50%
• BRCA2 mutation ranges from 12% to 20%
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43. copyright by Dave Carlson.
ANATOMY
• Ovarian cancer arises in the adnexae,
which consist of the:
• Ovaries
• Fallopian tubes
• Broad ligament
• Embryologic rests within the broad
ligament
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44. PATHOLOGY
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45. PATHOLOGY
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46. SCREENING AND PREVENTION
• Cancer Antigen 125
• expressed in approximately 75% of cases
• principally in the serous subtype
• not expressed by mucinous
• levels of CA 125 may not reflect intra-abdominal tumor burden
• Elevates in many benign gynecologic and nongynecologic conditions
• Not good for screening
• Uses:
• Helping to determine whether a pelvic mass is malignant
• Unknown primary origin?  ovary
• Response to systemic chemotherapy
• Surveillance of patients treated for ovarian cancer
• Screening for ovarian cancer in high-risk populations (i.e., patients with a strong family history
or BRCA1/2 mutation carriers)
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47. DIAGNOSIS
• Presentation:
• Abdominal swelling
• Abdominal pain
• Dyspepsia
• Urinary frequency
• Weight change Ascites
• Intestinal obstruction
• Evaluation:
• H&P
• Imaging: PET-CT
• Diagnostic laparoscopy
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48. STAGING – FIGO
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49. TREATMENT
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50. FOLLOW UP
• Clinic visit every 2-4 months for 2 years, then 3-6 months for 3 years,
then annually
• PE including pelvic exam
• Imaging TBCT, PETCT, MRI as clinically indicated
• CA-125 if initially elevated
• CBC and chemistry profile
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51. PROGNOSIS
• Prognostic factors associated with improved outcome:
• Early staging disease
• Younger age
• Low volume of residual disease (after debulking surgery)
• Good performance status
• Serous histology
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52. PROGNOSIS
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53. Thanks
15-Dec-19 Saeed Salman MD 53