Cervical Cancer - Meirovitz

Question 1

Describe the normal transformation zone and the squamocolumnar junction

Answer 1

NORMAL TRANSFORMATION ZONE
-ִcolumnar epithelium : single layer
-ִmetaplastic epithelium
at the SCJ
begins in the subcolumnar reserve cell stimulus : vaginal acidity, ִ
-gland openings
-ִNabothian cysts

• Starts at the basement membrane of squamous epithelium
• Multipotent cells: subcolumnar reserve cells
• Diffrentiate between squamous and reserve line
• Along columnar or squamous depend on stimuli (pH of vagina)

The transformation zone is from the original SCJ to the active SCJ

Question 2

What is CIN (cervical intraepithelial neoplasia)?

Answer 2

Cellular immaturity, disorganization, nuclear abnormalities and increased mitotic activity

Interferes with tumor suppressor genes in the body

lower third of epithelium : CIN I
-precancerous, usually regresses

Invasion into host DNA, most will reach the basement membrane and progress to cancer:
middle third of epithelium : CIN II
upper third of epithelium : CIN III

Question 3

What are the increased risk factors for cervical cancer?

Answer 3

HPV:
ִsexually active in mid adolescent years
ִmultiple sexual partners
ִlower socio - economic class
ִ“ high - risk “ partner

smoking : independent risk factor

Question 4

Which strains of HPV cause cancer and what are the other consequences?

What factors are involved in malignant transformation from the virus?

Answer 4

malignant transformation requires expression of viral E6 and E7 oncoproteins

ִmore than 100 types known today
ִLow risk : 6 , 11
ִHigh risk : 16, 18 (70% from these two), 31, 4

The vaccine protects against strains 16, 18, 6 and 11

Majority of strains don’t cause cancer but cause warts, condyloma, etc.

Multiple strain infection is common

Question 5

What is a pap smear for and when is it done?

Answer 5

In early phases is asymptomatic but detectable by screening (postcoital bleeding is uncommon)

ִannual PAP reduces chance of dying of cervical cancer from 4/1000 to 5/10000 - 90 % difference

ACOG recommends starting at age 21 and continuing until age 30 every two years (30% false negative)
After age 30 with 3 consecutive negative tests can continue every 3 years (chance of false negative 3x lower)

Screening is not diagnosis! Not valid for other malignancies. Detects squamous cell carcinoma (most common in the cervix) and adenocarcinoma (20%)

Low rate of false positives

If there is an evident abnormal cervix, do not pap smear, straight to biopsy

Question 6

What are the possible epithelial cell abnormalities detected in a pap smear and what action should be taken for them?

Answer 6

ִsquamous cells:
 ASCUS atypical squamous cells of undetermined
significance (3-5% will be dysplasia)
• ASC – H (30-50% risk of high grade dysplasia)
-Repeat smear/check HPV with DNA test

 LG SIL low grade squamous intraepithelial lesion
-corresponds to CIN I

 HG SIL high grade ssquamous intraepithelial lesion

• High risk for CIN II or III
• Biopsy! (to see how much is involved)

 squamous cell carcinoma
-biopsy

ִglandular cells
-rare
AGCUS
adenocarcinoma

Question 7

What is colposcopy?

What are the types of abnormal findings?

Answer 7

Low grade microscope used to guide biopsy by spotting the most pathological area of the cervix

Primarily magnification

Add acetic acid (vinegar)

• causes change of color to pathological areas
• areas of aceto-white epithelium (AWE)

Take biopsy from these AWE

ִkeratosis
ִaceto - white epithelium

ִpunctation (little dots)
ִmosaicism (patches of neovascularization)

ִatypical vessels

Question 8

What are the treatment options for CIN?

Answer 8

CONIZATION
ִdiagnostic and therapeutic
ִlimits of the lesion not seen with colposcopy
ִSCJ not seen with colposcopy
ִBiopsy or ECC with CIN II , III
LEEP: loop electro excision procedure (generally preserves fertilization)

HYSTERECTOMY
In cases of microinvasion
ִCIN seen at margins of cone
ִpoor compliance with follow up
ִother gynecologic problems requiring
hysterectomy
ִcancerophobia

Question 9

What are the pathways of spread of cervical cancer?

Answer 9

direct inavasion (of adjacent tissues)
 -cervical stroma, myometrium, vagina,  parametria (outside uterus, ligaments most common)

lymphatic metastases

• primary group:
• parametrial, paracervical, obturator, intenal and external iliac, sacral
• secondary group
• common iliac, inguinal, paraaortic

hematogenic
peritoneal implants

Question 10

How is cervical cancer staged?

Answer 10

CLINICAL STAGING: Stage does not change regardless of what is discovered in surgery!

Exam under anesthesia
ִCXR
ִIVP, US, CT (for hydronephrosis)
ִCystoscopy, rectoscopy (to see if rectum involved)

Stage 0: In situ (CIN I)

1: Confined to cervix

2: Beyond the cervix
2a: no parametrium, latest operable
2b: vagina and parametrium (no longer operable)

Spread to parametrial/peritoneal area, pelvic side walls, ureters, iliac vessels
Chemo and radiation as effective as surgery

3b: pelvic side wall or hydronephrosis
4: Distal metastasis to bladder or rectum

Question 11

How is cervical cancer treated?

Answer 11

Chemo used as radiation sensitizer (neoadjuvant)

Surgery or Chemoradiotherapy: Both methods have equivalent survival rate

Surgery:
Limited to stages I and IIa
Used in young women
-Radical hysterectomy and pelvic lymph node dissection
-Don’t need to remove ovaries

Chemoradiotherapy:
Can be used in all stages (I and IIa is the only time with a choice)
-Damages ovaries and causes fibrosis of vagina, uterus, and pelvic area
-If PET scan show distal lymph involvement won’t do surgery

Staging doesn’t change no matter what is found during surgery

After surgery: Chemoradiotherapy if:
ִpositive pelvic lymph nodes
ִdeep cervical invasion
ִparacervical invasion
ִpositive surgical margins