Ruth Olson
Normal Anatomy
Cervical Pathology
Notes
External os
Internal os
Endocervical cana
Transitional (transformation) zone: abrupt change
between squamous and glandular epithelium. When
you’re doing pap smears, this is the preferred site of
infection of HPV and the site where most dysplasia begins.
Visualize the cervix and where that zone begins while doing
a pap. The presence of metaplastic squamous cells or
mucus-secreting columnar cells indicates proper sampling.
Absence of these cells means that the pap smear must be
repeated.
Images
You can get invasion of glandular epithelium. Transition zone visible.
Benign Conditions
Acute cervicitis: STDs  gonococcus or Chlamydia(>50%);
also herpes et al. VERY COMMON. Clinical: vaginal
discharge (most common), perlvic pain, cervical os is
erythematous and may be covered by an exudate.
Chronic cervicitis:  squamous metaplasia of endocervical
mucosa. This obliterates mouth of mucus glands 
Nabothian cysts erosions and uclers, simulate ca. These
can get quite large.
Cervicitis is the primary source for conjunctivitis and
pneumonia in newborns.
Endocervical polyps: soft, edematous stroma, epi-covered
may erode  bleed. Arises from ENDOCERVIX NOT CERVIX
“Pill” cervix: microglandular hyperplasia (progesterone
effect?)
Microglandular hyperplasia of endocervix (pill cervix).
Atypical cells may be seen on PAP smear.
Nabothian cyst. Multiple mucus filled Nabothian cysts (cervical canal has been opened)
Endocervical polyp protruding from cervix. Whole mount of benign endocervical polyp
(arrow points to ectocervix). Polyp has sq. and gland tissue. Rx: surgical excision.
Ruth Olson
Epidemiology
Risk Factors
HPV
Cervical Pathology
50,000 precancerous cases/yr, but 13,000 invasive/yr (75%
prevented-Rx or spontaneous regression). Before we were
aggressive in interventions, most would regress.
13,000 invasive cases/yr, but <5,000 die (60% cure rate)
Papanicolaou smear = effective at identifying precancerous
lesions.
One of few examples of value of early cancer detection!
Historically: it’s been a deadly disease affecting younger
women. We have a way to eradicate it now.
Average age: 45 yo. Normally progression from CIN IIII is
~10 years.
early age of first sexual intercourse
multiple sexual partners
male partner who has multiple other partners
penile condylomas
All of these things imply a sexually transmitted agent
HPV!
-Causes condyloma accuminatum & warts (virus remains
episomal)
-Types 16, 18, 31, 33 stainable in precancerous cervical
mucosa (virus integrates into host genome)
-Transforms squamous epithelial cells in vitro
-E6 oncoprotein product of HPV binds with and degrades
p53 inhibits apoptosis
-E7 oncoprotein binds hypophosphorylated pRb,
frees E2F transcription factor to drive cell cycle
-double whammy on the cell cycle
-HPV virus (Human papillomavirus) found in ~90% of
tumors
-HPV infected cells called koilocytes inc nuclear size, inc
Nuclear/Cytoplasmic ratio, irregular nuclear
contoursraisenoid, hyperchromasia and perinuclear
clearing
mitoses
Roll of the E7 oncogene  binds to E2F activates transcriction (S phase genes) in
conjunction with pRb gene.
This chart measures
association of HPV types
with Condylomas, CIN
IIII and invasive ca.
HPV types 16 & 18 are
found in high-grade
cervical lesions. 6 & 11 in
condylomas
Ruth Olson
Classification of
precancerous lesion
Cervical Pathology
cervical intraepithelial neoplasia: CIN
Progresses through succession (CIN I II  III) of
moderate, severe (same as CIN III)
CIN III also called “carcinoma in situ”
Grades of cervical dysplasia: level at which atypical cells are present
Nuclei are at first oriented perpendicularly to BM and lumen; then they flatten out; then they
become piknotic. As it progresses, the amount of dysplasia increases (1/32/33/3).
PROGRESSION FROM IIII IS NOT INEVITABLE.
Histology of
Dysplasia
Ruth Olson
Cervical Pathology
Histology cont.
Biological Features
-% of cases progressing to next-highest grade ­ with the
grade (i.e., % CIN II  III more that III)
-lesions begins @ squamo-columnar junction
(“transformation zone”)
-initial lesions may be any grade
-time in any grade varies from months to many years
-detection: iodine (Schiller’s) test—stains glycogen in
normal cells
-Extends down into the vagina, extends out into the lateral
wall of the cervix and vagina, infiltrates the bladder wall
and obstrucs the ureters post-renal axotemia leading to
renal failure is a common cause of death.
-70-85% are squamous cell carcinoma. Small cell cancer
and adenocarcinoma are less common types.
CLINICAL: Abnormal bleeding (usu pos-coital), malodorous
discharge.
DIagnosis
screening: “pap” smear
definitive diagnosis:
pap smear repeat
colposcopy: Schiller test, biopsy visible lesion, conization
follow: with repeat smears & colposcopy
Most lower-grade lesions regressed. More from the moderate progressed than the mild.
COMPARISON OF TRADITIONAL, CIN & BETHESDA NOMENCLATURE
Traditional Cervical Intraepithelial Neoplasia (CIN)
Bethesda System
HPV (flat condyloma)
N/A
Low-grade squamous
Mild dysplasia
CIN I
Moderate
CIN II
High-grade squamous
intraepithelial lesion
(SIL)
Severe dysplasia
CIN III
Carcinoma-in-situ
Ruth Olson
Cervical Pathology
Invasive carcinoma
type: 80% = squamous cell carcinoma
remainder: undifferentiated, adenosquamous &
adenocarcinoma
In DES-Rxed patients = clear cell carcinoma
Staging of invasive cervical cancer:
Stage 0: CIN III
Stage I: limited to cervix
Stage II: beyond cervix, upper 1/3 vagina, does not
reach pelvic wall
Stage III:lower 1/2 vagina & reaches pelvic wall
Stage IV:beyond pelvis or invaded bladder or colon;
distant metastases
Rx
CIN I, II, III: pap, cryoRx, laser, conization, wire loop
invasive: hysterectomy and radioRx
Prognosis: stage-dependent
Stage I = 90% 5 yr
Stage III = 10%
Complications: local invasion  bladder, ureters, colon
Female cancer death rate due to uterus cancer is
decreasing!
Ulcerated squamous cell carcinoma of cervix
Poorly differentiated
Normal glands (green arrow) vs glands of adenocarcinoma of cervix .
Ruth Olson
Cervical Pathology
Questions:
1.
2.
3.
4.
5.
6.
7.
8.
What is the most important zone to obtain cells from in a pap smear?
What two organisms cause the most cases of acute cervicitis?
Which benign condition has soft, edematous stroma, is epithelium covered, and may erode, causing bleeding?
Name risk factors for HPV infection.
Name the 2 oncoproteins associated with the development of cancer.
Which two subtypes are associated with cervical cancer? Condylomas?
T/F CIN II is more likely to progress to CIN III than CIN I is to progress to CIN II
Define stages O IV of cervical cancer.
Answers:
1. Transitional zone
2. Gnoncoccus and Chlamydia.
3. Endocervical polyp
4.
early age of first sexual intercourse
multiple sexual partners
male partner who has multiple other partners
penile condylomas
5. E6 and E7
6. 16,18. 6,11
7. True
8. Staging of invasive cervical cancer:
Stage 0:
CIN III
Stage I: limited to cervix
Stage II: beyond cervix, upper 1/3 vagina, does not reach pelvic wall
Stage III:lower 1/2 vagina & reaches pelvic wall
Stage IV:beyond pelvis or invaded bladder or colon; distant metastases